IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

Radiation-induced lung injury - what do we know in the era of modern radiotherapy?

Radiation-induced lung injury (RILI) that is usually divided into an early radiation-induced pneumonitis (RIP) and late chronic radiation-induced lung fibrosis (RILF) remains a clinically significant toxicity in radiation oncology. Thus, a thorough understanding of underlying molecular mechanisms and risk factors is crucial. This review, focused on patients treated with modern radiotherapy (RT) techniques, describes the different clinical presentations of RIP, with most typical imaging findings and usefulness of pulmonary function tests and laboratory assessment in differential diagnosis. The most critical patient- and treatment-related predictors are summarized and discussed - age and sex, comorbidities, tumour characteristics, concomitant treatment, and RT-plan parameters. The conventional grading scales and contemporary approach to quantitative assessment (radiomics, CT density changes) is described as well as treatment methods.

FLASH radiotherapy: an emerging approach in radiation therapy.

FLASH radiotherapy (RT) is a technique involving the delivery of ultra-high dose rate radiation to the target. FLASH-RT has been shown to reduce radiation-induced toxicity in healthy tissues without compromising the anti-cancer effects of treatment compared to conventional radiation therapy. In the present article, we review the published data on FLASH-RT and discuss the current state of knowledge of this novel approach. We also highlight the technological constraints and complexity of FLASH-RT and describe the physics underlying this modality, particularly how technology supports energy transfer by ionising radiation (e.g., beam on/off sequence, pulse-energy load, intervals). We emphasise that current preclinical experience is mostly based on FLASH electrons and that clinical application of FLASH-RT is very limited. The incorporation of FLASH-RT into routine clinical radiotherapy will require the development of devices capable of producing FLASH photon beams.

Improving radiation oncology through clinical audits: Introducing the IROCA project.

As radiotherapy practice and processes become more complex, the need to assure quality control becomes ever greater. At present, no international consensus exists with regards to the optimal quality control indicators for radiotherapy; moreover, few clinical audits have been conducted in the field of radiotherapy. The present article describes the aims and current status of the international IROCA "Improving Radiation Oncology Through Clinical Audits" project. The project has several important aims, including the selection of key quality indicators, the design and implementation of an international audit, and the harmonization of key aspects of radiotherapy processes among participating institutions. The primary aim is to improve the processes that directly impact clinical outcomes for patients. The experience gained from this initiative may serve as the basis for an internationally accepted clinical audit model for radiotherapy.

The rationale for HPV-related oropharyngeal cancer de-escalation treatment strategies.

The treatment paradigms for head and neck squamous cell cancer (HNSCC) are changing due to the emergence of human papillomavirus-associated tumors (HPV-related), possessing distinct molecular profiles and responses to therapy. Retrospective studies have suggested that HPV-related HNSCCs are more frequently cured than those caused by tobacco. Current clinical trials focus on the reduction of treatment-related toxicity and the development of HPV-targeted therapies. New treatment strategies include: 1) dose reduction of radiotherapy, 2) the use of cetuximab instead of cisplatin for chemo-radiation 3) less invasive surgical options, i.e. trans-oral robotic surgery and trans-oral laser microlaryngoscopy, and 4) more specific treatment attempts, including immunotherapeutic strategies, thanks to increasing comprehension of the molecular background of HPV-related HNSCC. Whereas recently published data shed light on immune mechanisms, other studies have focused on specific vaccination against HPV-related HNSCC. A crucial problem is patient selection to the chosen bias. Truly HPV-related cancers (p16-positive and HPV DNA-positive) with biomarkers for good response to therapy could be included in randomized trials aiming for less severe and better tailored therapy.

Hormone therapy in combination with radiotherapy in the treatment of prostate cancer: why and in which group of patients?

In recent years, significant development in the treatment of prostate cancer has taken place. One of the most documented methods of treatment in patients characterised by a high risk of progression is a combination of radiotherapy (RT) with long-term hormone therapy (HT). In this group of patients, neither RT alone nor HT alone allows satisfactory outcomes to be achieved, and therefore as monotherapy they are not recommended as optimal methods of treatment. In this review, we summarise arguments for combining radiotherapy with hormonal therapy in high-risk prostate cancer, with an emphasis on the results of phase III trials.

Management of bone metastases in patients with castration-resistant prostate cancer.

Bone metastases are a very common problem in prostate cancer. They are associated with considerable morbidity, adversely affect quality of life and frequently lead to advanced bone events (so-called skeletal-related events, SREs); SREs include fractures, spinal cord compression and the requirement for bone surgery or bone radiation. The aim of this paper was to evaluate currently available treatment options in the prevention and management of SREs and bone metastases in men with castration-resistant prostate cancer and to outline the importance of interdisciplinary management strategies. It also discusses the diagnostic workup of osseous metastases and practical considerations for the utilization of bone-targeted therapies in accordance with current guidelines to provide a consensus for special and/or difficult clinical situations.

The use of luteinizing hormone-releasing hormone analogues is still an indispensable element of therapy in castrate-resistant prostate cancer.

Metastatic prostate cancer, which shows progression despite castration testosterone levels, was previously defined as hormone-refractory. This definition has recently been changed to the one presently used - castrate-resistant prostate cancer. Numerous fundamental studies have provided evidence that the development of hormone-refractory prostate cancer is constantly dependent on the concentration of androgens. The aim of the metastatic castrate-resistant prostate cancer (mCRPC) treatment is currently to obtain the lowest possible androgen concentration. The effectiveness of such management has been proven by the results of clinical studies on the latest hormonal and chemotherapeutic medications. In the last two decades, new effective chemotherapeutics have become available on the market: abiraterone, enzalutamide, docetaxel, cabazitaxel, zoldronic acid, denosumab and alpharadin They significantly contribute to extending patients' survival and to improving their quality of life. Therefore, the question arises whether using luteinizing hormone-releasing hormone (LHRH) analogues is still a necessary element of the therapy. A detailed analysis of study regimens involving the above-mentioned medications and of available publications supports the view that LHRH analogues are the basic strategy in the treatment of patients with mCRPC. All clinical trials evaluating new therapies still followed the principle of obtaining castration testosterone levels as a result of using LHRH analogues simultaneously with the new medications.

Opportunities for rehabilitation of patients with radiation fibrosis syndrome.

This review discusses the pathophysiology, evaluation, and treatment of neuromuscular, musculoskeletal, and functional disorders that can result as late effects of radiation treatment. Although radiation therapy is often an effective method of killing cancer cells, it can also damage nearby blood vessels that nourish the skin, ligaments, tendons, muscles, nerves, bones and lungs. This can result in a progressive condition called radiation fibrosis syndrome (RFS). It is generally a late complication of radiotherapy which may manifest clinically years after treatment. Radiation-induced damage can include "myelo-radiculo-plexo-neuro-myopathy," causing muscle weakness and dysfunction and contributing to neuromuscular injury. RFS is a serious and lifelong disorder which, nevertheless, may often be decremented when identified and rehabilitated early enough. This medical treatment should be a complex procedure consisting of education, physical therapy, occupational therapy, orthotics as well as medications.

Physical activity and body composition, body physique, and quality of life in premenopausal breast cancer patients during endocrine therapy--a feasibility study.

UNLABELLED: Endocrine therapy (ET) is a common method of treatment in breast cancer patients; however, its negative impact on body composition, body physique (physical body shape/measurements), and quality of life (QoL) remains controversial. Previous studies have shown physical exercise can have a positive effect on QoL in breast cancer patients, especially premenopausal subjects. OBJECTIVE: In this feasibility study, we sought to assess the impact that physical exercise had on body composition and QoL in premenopausal breast cancer patients undergoing ET, and to determine the appropriateness of further testing of this intervention in this patient group. MATERIAL AND METHODS: This study involved 41 premenopausal female breast cancer patients before and after six, 12, and 18 months of ET. Aerobic training began in the 6th month and resistance training was added in the 12th month. Body composition was evaluated using dual-energy x-ray absorptiometry (DXA) scans, body physique was evaluated using anthropometric measurement techniques, and QoL was evaluated using questionnaires from the European Organization for Research and Treatment of Cancer. RESULTS: The initial period of ET with no exercise resulted in a reduction in fat-free body mass (FFBM), an increase in fat body mass (FBM), and a decline in QoL scores. Adding aerobic training resulted in a reduction of FBM and percentage of android fat, and improved QoL scores. The introduction of resistance training further reduced percentage of android and gynoid fat, increased FFBM, and further improved QoL scores. CONCLUSION: ET negatively impacts body composition, body physique, and QoL of premenopausal breast cancer patients. This feasibility study shows that physical activity may improve QoL and reduce adverse effects of ET on body composition and body physique, indicating appropriateness for further investigation on the use of exercise programs in premenopausal breast cancer patients to improve the outcomes of therapy.

The impact of aerobic exercises on bone mineral density in breast cancer women during endocrine therapy.

BACKGROUND: The assessment of the impact aerobic exercises on bone mineral density in breast cancer women during endocrine therapy (ET). MATERIAL/METHODS: The study included 53 women (mean 44.3 ±SD 4.9) during breast cancer treatment. This was a nonrandomized, prospective clinical study. The following examinations of the assessment of bone in the DEXA were measured: the bone mineral density of the neck of a femur (FN), lumbar region L1-L4, and total body (TB) as well as defining of T-score and Z-score. The examinations were conducted for all the patients according to the schedule: before the beginning of ET, after 6 months of ET and after 12 months of ET (after 6 month aerobic training). RESULTS: After the first 6 months of ET without regular physical exercise the following results were noted: the BMD mean value of FN, in the L1-L4 spine region and in TB were significant lower than the initial value. After 6 month aerobic training, in the 12th month of the follow up, the BMD mean value of FN was 1.1% (p>0.05) lower, while in the L1-L4 spine region it was 5.6% (p<0.05) lower, and in TB 2.7% (p<0.05) lower in comparison to the values in the sixth month of the observation. CONCLUSIONS: That even short course of ET is related to changes in bone mineral density. The introduction of aerobic exercises caused a slowdown in negative changes in bones.

Total skin electron irradiation techniques: a review.

Total skin electron irradiation (TSEI) has been employed as one of the methods of mycosis fungoides treatment since the mid-twentieth century. In order to improve the effects and limit the complications following radiotherapy, a number of varieties of the TSEI method, frequently differing in the implementation mode have been developed. The paper provides a systematic review of the different varieties of TSEI. The discussed differences concerned especially: (i) technological requirements and geometric conditions, (ii) the alignment of the patient, (iii) the number of treatment fields, and (iv) dose fractionation scheme.

Exercise tolerance in breast cancer patients during radiotherapy after aerobic training.

AIM OF THE STUDY: In spite of the introduction of dose constraints based on patient individual assessment techniques for radiation therapy (RT), some side effects from the heart and lungs are observed. Regular physical exercises improve efficiency, which was confirmed in clinical trials. The aim of this study was to evaluate endurance exercise tolerance and the impact of aerobic training (AT) on selected clinical parameters in breast cancer patients during RT. MATERIAL AND METHODS: This study involved 46 women with breast cancer who were irradiated using conformal technique (3DCRT) to a total dose of 50 Gray during a 5-week course of RT. In this period 25 patients (group A) simultaneously performed AT, and the rest of the patients, without rehabilitation (group B), undertook irregular physical activity on their own. The exercise tolerance was assessed through the 6-minute walk test (6MWT) using: oxygen saturation (SO2), heart rate (HR), blood pressure (BP), 6-minute walk distance (6MWD) and dyspnea scale. RESULTS: After AT in group A, a statistically significant (p < 0.05) decrease was observed in average diastolic BP before 6MWT and in HR parameters before and after 6MWT (p > 0.05), and 6MWD was increased (p < 0.05). In group B, after RT, an increase (p < 0.05) in HR was observed after the test as well as dyspnea. Oxygen saturation in both groups was not significantly changed. CONCLUSIONS: The results of our study showed that regular AT after just 6 weeks caused an improvement in exercise tolerance parameters with a substantial decline in dyspnea in breast cancer patients receiving RT.

Intraoperative radiation therapy as part of breast conserving therapy of early breast cancer-Results of one-year follow-up.

AIM: The aim of this study was to assess the therapeutic effect of intraoperative radiotherapy, describe the method, and examine the occurrence of side effects and quality of life. BACKGROUND: Breast conserving therapy has recently become a standard treatment modality in patients with early invasive cancer. Radiotherapy, along with surgery, is an integral part of such treatment. The important thing of radiotherapy is to deliver a high dose to the tumour bed. One of the methods is the intraoperative radiotherapy. MATERIALS AND METHODS: The analysis comprised sixty Tis-T2N0-1A breast cancer patients treated with breast conserving surgery. Patients' mean age was 57 years (range: 32-73 years). Intraoperative radiation therapy was delivered in the operating theatre during surgery and involved a single dose of 10 Gy with an electron beam of 4, 6, 9 or 12 MeV. After that, all patients were treated with whole breast irradiation. During one year observation photos and side effects examination were made. RESULTS: Physical and imaging examinations performed during a one-year follow-up revealed no local or distant relapse and good tolerance of IORT. Acute mild responses to the radiotherapy occurred in 23.3% of patients. Based on the examination, a good and very good cosmetic effect was found in 78.3%, with 83.3% of patients evaluating their treatment effects in the same way. CONCLUSIONS: Due to its exceptional physical and radiobiological properties, intraoperative radiation therapy can be a good alternative to other methods of boosting dose to the post-operative site in management of low stage breast cancer, enabling a precise therapy to the tumour bed.

Large Prostate Volume Does Not Negatively Impact Health-Related Quality of Life in Patients with Prostate Cancer Treated with Ultrahypofractionated Stereotactic Body Radiotherapy.

BACKGROUND: Survival outcomes after primary radiotherapy for localized prostate cancer (PCa) are excellent, regardless of the specific treatment modality. For this reason, health-related quality of life (HRQOL) has come to play an ever more important role in treatment selection. Stereotactic body radiation therapy (SBRT) is increasingly used to treat patients with PCa. However, the impact of prostate volume on HRQOL is not clear. In this study, we aimed to determine whether a large prostate volume negatively influences HRQOL outcomes in patients undergoing ultrahypofractionated SBRT. MATERIAL AND METHODS: We conducted a prospective study of 530 men with low- and intermediate-risk localized PCa. All patients were treated from 2013 to 2017 with SBRT (Cyberknife system). HRQOL data were collected at baseline (pre-treatment), immediately after treatment, and at 12 and 24 months. QOL variables were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 and PR-25 module. Differences in the QLQ-C30 scales were considered clinically relevant when the change was >10 points. For the analysis, patients were classified into two groups according to prostate volume (≤60 vs. >60 cm3). RESULTS: The prostate volume was ≤60 cm3 in 415 patients (78.3%) and >60 cm3 in 115 (21.7%). No between-group differences were observed at baseline for any of the following variables: clinical stage; hormonal therapy; marital status; educational level; or employment status. No clinically-significant deterioration (functional and symptom scales) was observed in either group between the baseline and 24-month assessment. There were no clinically-relevant differences between the groups on any of the HRQOL variables, regardless of the prostate volume. CONCLUSIONS: This study shows that a large prostate volume (>60 cm3) does not appear to negatively impact HRQOL outcomes at two years in patients with localized prostate cancer treated with ultrahypofractionated SBRT administered with the CyberKnife system.

Radiotherapy planning in a prostate cancer phantom model with intraprostatic dominant lesions using stereotactic body radiotherapy with volumetric modulated arcs and a simultaneous integrated boost.

Aim: In the treatment of prostate cancer with radiation therapy, the addition of a simultaneous integrated boost (SIB) to the dominant intraprostatic lesions (DIL) may improve local control. In this study, we aimed to determine the optimal radiation strategy in a phantom model of prostate cancer using volumetric modulated arc therapy for stereotactic body radiotherapy (SBRT-VMAT) with a SIB of 1-4 DILs. Methods: We designed and printed a three-dimensional anthropomorphic phantom pelvis to simulate individual patient structures, including the prostate gland. A total of 36.25 Gy (SBRT) was delivered to the whole prostate. The DILs were irradiated with four different doses (40, 45, 47.5, and 50 Gy) to assess the influence of different SIB doses on dose distribution. The doses were calculated, verified, and measured using both transit and non-transit dosimetry for patient-specific quality assurance using a phantom model. Results: The dose coverage met protocol requirements for all targets. However, the dose was close to violating risk constraints to the rectum when four DILs were treated simultaneously or when the DILs were located in the posterior segments of the prostate. All verification plans passed the assumed tolerance criteria. Conclusions: Moderate dose escalation up to 45 Gy seems appropriate in cases with DILs located in posterior prostate segments or if there are three or more DILs located in other segments.

Algorithms of follow-up in patients with head and neck cancer in relation to primary location and advancement. Consensus of Polish ENT Society Board and Head Neck Experts.

Summary: The algorithm of follow-up in patients with head and neck cancer (HNC) has been prepared by a board of Polish Head Neck and Oncology Experts. The aim of this research is to focus on the specificity of HNC monitoring, to review the current trends in follow-up, and to adapt the evidence-based medicine international standards to the capabilities of the local healthcare service. Materials and methods: The first methodological step was to categorize HNCs according to the estimated risk of failure after the adequate first-line treatment and according to the possibility of effective salvage treatment, resulting in improved overall survival. The final method used in this work was to prepare an authors' original monitoring algorithm for HNC groups with a high, moderate, and low risk of recurrence in combination with a high or low probability of using an effective salvage. Results: Four categories were established: Ia. low risk of recurrence + effective organ preservation feasible; Ib. low risk of recurrence + effective salvage feasible; II. moderate risk of recurrence + effective salvage feasible; III. high risk of recurrence + effective salvage feasible; and IV. high risk of recurrence + no effective salvage feasible. Follow-up visit consisting of 1. ENT examination + neck ultrasound, 2. imaging HN tests, 3. chest imaging, 4. blood tests, and 5. rehabilitation (speech and swallowing) was scheduled with a very different frequency, at the proposed monthly intervals, tailored to the needs of the group. The number of visits for individual groups varies from 1 to 8 in the first 2 years and from 1 to 17 in the entire 5-year monitoring period. Group IV has not been included in regular follow-up, visits on own initiative of the patient if symptomatic, or supportive care needs, having in mind that third-line therapy and immune checkpoint inhibitors are available. Conclusion: Universal monitoring algorithm for HNC four groups with a high, moderate, and low risk of recurrence after the adequate treatment in combination with a high or low probability of using an effective salvage is an innovative approach to redeploying system resources and ensuring maximum benefit for patients with HNC.

Baseline CTC Count as a Predictor of Long-Term Outcomes in High-Risk Prostate Cancer.

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at least 5 years. CTCs were enumerated using three different assay formats in 104 patients: the CellSearch® system, EPISPOT assay and GILUPI CellCollector. A total of 57 (55%) patients survived until the end of the follow-up period, with a 5 year OS of 66% (95% CI: 56-74%). The analysis of univariate Cox proportional hazard models identified a baseline CTC count ≥ 1, which was determined with the CellSearch® system, a Gleason sum ≥ 8, cT ≥ 2c and metastases at initial diagnosis as significant predictors of a worse OS in the entire cohort. The CTC count ≥ 1 was also the only significant predictor of a worse OS in a subset of 85 patients who presented with localized PCa at the baseline. The baseline CTC number did not affect the MFS. In conclusion, the baseline CTC count can be considered a determinant of survival in high-risk PCa and also in patients with a localized disease. However, determining the prognostic value of the CTC count in patients with localized PCa would optimally require longitudinal monitoring of this parameter.

Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study.

BACKGROUND: Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. METHODS: In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. FINDINGS: 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9-18·5) for patients on denosumab and 11·2 months (IQR 5·6-17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8-24·9) with denosumab compared with 17·1 months (15·0-19·4) with zoledronic acid (hazard ratio 0·82, 95% CI 0·71-0·95; p = 0·0002 for non-inferiority; p = 0·008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0·0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p = 0·09). INTERPRETATION: Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer. FUNDING: Amgen.

Investment in radiotherapy infrastructure positively affected the economic status of an oncology hospital.

BACKGROUND: Radiotherapy is among the most efficient treatment methods of cancer. However, a radiotherapy base needs a substantial financial investment, especially before the beginning of its operation, and in some cases, in developing countries such a huge investment may cause some financial disturbances for a hospital concerned. AIM: To assess the influence of investments modernizing the radiotherapy base in the period between 2000 and 2007 on the financial condition of the oncology hospital in the region with population of about 3 million. MATERIAL AND METHODS: Financial reports and medical statistics for the period between 2000 and 2007 from the studied oncology hospital and a recognized staffing model, as well as data on epidemiological situation of the region have been used to calculate the economic effects of financial investment in the radiotherapy base. RESULTS: The growth of RT therapeutic potential has been driven by two cost-effective investment programmes. The total amount invested in both programmes was PLN 127,191,000. The number of radiotherapy patients treated in the hospital increased from 2301 in 2000 to 4799 in 2007 with a the same number of five therapeutic machines, although all five of them were replaced over that period. Investments modernizing the radiotherapy base lead to a significant increase in depreciation and operating costs, which adversely affects financial results of the hospital. CONCLUSION: Long term trends showed that investments had positive influence on hospital performance shown both in increased income and larger number of patients treated.