Stereotactic Ablative Radiotherapy Using CALYPSO® Extracranial Tracking for Intrafractional Tumor Motion Management-A New Potential Local Treatment for Unresectable Locally Advanced Pancreatic Cancer? Results from a Retrospective Study.

(1) Background: The aim of this study was to evaluate the efficacy and safety of SABR for LAPC using Calypso® Extracranial Tracking for intrafractional, fiducial-based motion management, to present this motion management technique, as there are yet no published data on usage of Calypso® during SABR for LAPC, and to report on our clinical outcomes. (2) Methods: Fifty-four patients were treated with SABR in one, three, or five fractions, receiving median BED10 = 112.5 Gy. Thirty-eight patients received systemic treatment. End points were OS, FFLP, PFS, and toxicity. Actuarial survival analysis and univariate analysis were investigated. (3) Results: Median follow-up was 20 months. Median OS was 24 months. One-year FFLP and one-year OS were 100% and 90.7%, respectively. Median PFS was 18 months, and one-year PFS was 72.2%. Twenty-five patients (46.3%) were alive at the time of analysis, and both median FU and OS for this subgroup were 26 months. No acute/late toxicity > G2 was reported. (4) Conclusions: SABR for LAPC using Calypso® presented as an effective and safe treatment and could be a promising local therapeutic option with very acceptable toxicity, either as a single treatment or in a multimodality regimen. Dose escalation to the tumor combined with systemic treatment could yield better clinical outcomes.

An Evaluation of Total Internal Motions of Locally Advanced Pancreatic Cancer during SABR Using Calypso® Extracranial Tracking, and Its Possible Clinical Impact on Motion Management.

(1) Background: the aims of this study were to determine the total extent of pancreatic cancer's internal motions, using Calypso® extracranial tracking, and to indicate possible clinical advantages of continuous intrafractional fiducial-based tumor motion tracking during SABR. (2) Methods: thirty-four patients were treated with SABR for LAPC using Calypso® for motion management. Planning MSCTs in FB and DBH, and 4D-CTs were performed. Using data from Calypso® and 4D-CTs, the movements of the lesions in the CC, AP and LR directions, as well as the volumes of the 4D-CT-based ITV and the volumes of the Calypso®-based ITV were compared. (3) Results: significantly larger medians of tumor excursions were found with Calypso® than with 4D-CT: CC: 29 mm (p < 0.001); AP: 14 mm (p < 0.001) and LR: 11 mm (p < 0.039). The median volume of the Calypso®-based ITV was significantly larger than that of the 4D-CT based ITV (p < 0.001). (4) Conclusion: beside known respiratory-induced internal motions, pancreatic cancer seems to have significant additional motions which should be considered during respiratory motion management. Only direct and continuous intrafractional fiducial-based motion tracking seems to provide complete coverage of the target lesion with the prescribed isodose, which could allow for safe tumor dose escalation.

THE ROLE OF COMPLETE BLOOD COUNT PARAMETERS IN PATIENTS WITH COLORECTAL CANCER.

- Chronic inflammation has been linked with many cancers. It seems that easily available and usual blood inflammatory markers might serve as a prognostic factor for overall survival and disease-free survival in patients with various cancers. Preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as hemoglobinemia, thrombocytosis, elevated C-reactive protein values, neutropenia and leukocytosis have been shown to affect overall survival and disease-free survival in patients with colorectal cancer (CRC), however, with controversial results. Complete blood count, NLR and PLR were determined in 71 patients with CRC (stages 3 and 4) after neoadjuvant chemo-radiotherapy and before surgery, treated at Hospital for Tumors in Zagreb. Statistical analysis included Mann-Whitney U test, Student's t-test, univariate and multivariate analysis. The results of Mann-Whitney U test and Student's t-test showed that neutrophil count (p=0.024), NLR (p=0.003) and PLR (p=0.007) correlated significantly with overall survival. However, there was no significant correlation of age, leukocyte, lymphocyte and platelet counts and hemoglobin values with overall survival of patients. Furthermore, the same tests showed that leukocyte (p=0.04), neutrophil (p=0.0014) and platelet (p=0.006) counts, NLR (p=0.0006) and PLR (p=0.0015), as well as hemoglobin values (p=0.028) correlated significantly with disease-free survival. The results of univariate analysis showed that unlike PLR, NLR correlated with overall survival and disease-free survival (p=0.0002), although the correlation of PLR and disease-free survival almost reached significance (p=0.059). Furthermore, the results of univariate analysis showed significant correlation of advanced pathological TNM stage with overall survival. There was no correlation of patient age and gender, tumor stage and neoadjuvant chemo-radiotherapy with overall survival and disease-free survival. The results of multivariate analysis showed that NLR (cut-off value 3.27) and advanced pathological TNM stage significantly correlated with disease-free survival but not with overall survival. It seems that NLR might be an accurate marker for overall survival and disease-free survival in CRC patients after neoadjuvant chemo-radiotherapy and before surgery.

[Influence of daily set-up errors on dose distribution during pelvis radiotherapy]. / Utjecaj Pogreske U Polozaju Bolesnikatijekom Zracenja Zdjelice Na Raspodjeludoze.

An external beam radiotherapy (EBRT) using megavoltage beam of linear accelerator is usually the treatment of choice in cancer patients. The goal of EBRT is to deliver the prescribed dose to the target volume, with as low as possible dose to the surrounding healthy tissue. A large number of procedures and different professions involved in radiotherapy, uncertainty of equipment and daily patient set-up errors can cause a difference between the planned and delivered dose.We investigated a part of this difference caused by measuring daily patient set-up errors for 35 patients. These set-up errors were simulated on five patients, using 3D treatment planning software XiO. The simulation investigated differences in dose distributions between the planned and shifted geometry. Additionally, we investigated the influence of the error on treatment plan selection by analysing changes in dose volume histograms, planning target volume conformity index (CIPTV), and homogeneity index (HI).Simulations showed that patient daily set-up errors can cause significant differences between the planned and actual dose distributions. Moreover, for some patients, those errors could affect the choice of treatment plan since CIPTV fell under 97%. Surprisingly, HI was not as sensitive to set-up errors as CIPTV. Our results have confirmed the need to minimise daily set-up errors through quality assurance programmes.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with colorectal cancer]. / Klinicke upute za dijagnozu, lijecenje i pracenje bolesnika oboljelih od kolorektalnog raka.

Colorectal cancer is the third most common malignant tumour in males and the fourth most common malignancy in women in the Republic of Croatia. It is usually manifested as stool forming disorders, feeling that bowel does not empty completely, finding blood in the stool, weight loss and fatigue. In-time diagnosis, confirmed by pathohistological findings, is cornerstone of successful treatment. The decision about treatment is made based on clinical assessment of disease stage and other risk factors, after completion of the diagnostic process. Depending on that, treatment options include surgery, the application of systemic therapy (chemotherapy, immunotherapy) and radiotherapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, treatment and monitoring of patients with colorectal cancer in the Republic of Croatia.

Immunohystochemical expression of cancer/testis antigens (MAGE-A3/4, NY-ESO-1) in non-small cell lung cancer: the relationship with clinical-pathological features.

The aim of this study was to explore the expression of cancer/testis tumor associated antigens (C/T TAAs) MAGE-A 3/4 and NY-ESO-1 in lung squamous cell carcinoma and adenocarcinoma, and to evaluate their association with the standard clinical-pathological features of surgically treated lung cancer patients. The study included 80 patients with non-small cell lung cancer (40 adenocarcinomas, 40 squamous cell carcinomas) who had undergone surgery in the period between 2002 and 2005. The MAGE-A3/4 and NY-ESO-1 antigen expression was analyzed immunohistochemically (IHC). The results showed MAGE-A3/4 and NY-ESO-1 positive staining in 65.1% and 23.3% of squamous cell carcinomas and 18.9% and 10.8% of adenocarcinomas, respectively. A statistically higher MAGE-A3/4 expression was observed in planocellular bronchial carcinoma (p < 0.001), while no difference was found in the expression of NY-ESO-1 in adenocarcinoma and planocellular carcinoma (p = 0.144). A significant association was found between the MAGE-A3/4 expression and presence of tumor necrosis in squamous cell cancer specimens (p = 0.001), but not in adenocarcinoma (p = 0.033). A statistically significant association was noted between the NY-ESO-1 expression and positive hilar and mediastinal lymph nodes in adenocarcinoma (p = 0.025) whereas it was not the case in squamous cell carcinoma. Non-small cell lung cancer frequently expresses cancer/testis tumor associated antigens. Our results demonstrate that the MAGE-A3/4 and NY-ESO-1 expression was significant associated with prognostic factors of poor outcome of disease (presence of tumor necrosis and lymph node metastasis). As C/T antigens are important for inducing a specific immune reaction in lung cancer patients, there is an intention to form a subgroup of patients in the future, whose treatment would be enhanced by specific immunotherapy based on the observed scientific results.

[Distinction between medical error and complication in indemnification of damage]. / Razlika izmedu pogreske i komplikacije u naknadi stete.

There are many articles present in literature dealing with the difference between the medical error and the complication in indemnification of damage caused by the medical act. It is a very challenging and sometimes even impossible task. The criteria usually used are defined by the accumulated medical knowledge and the complexity of interactions and conditions under which the medical service is provided. Contemporary medicine is reaching increasingly better results aiming to treat the rapidly ageing population. Consequently, the expectations of patients are growing, and sometimes exceeding reality. Ever more aggressive interventions are being introduced for diagnostic and treatment purposes of conditions, recently considered incurative. Some patients inevitably suffer harm from professional mistakes or from the disease course or complications. The difficulties we face when trying to differentiate cause of the harm often lead to misunderstandings in the general public or the public media, and undermine the confidence regarding the public health system. In this article, the difference between medical error and complication in indemnification of damage is discussed in details.