Prolonged treatment planning can increase real rectal dose in 3D brachytherapy for cervical cancer.

PURPOSE: The purpose of this study was to evaluate the influence of 3D brachytherapy planning time on the real dose distribution. MATERIAL AND METHODS: 10 patients with cervical cancer were evaluated using 2 computed tomography (CT) scans brachytherapy. The first scan was performed after the insertion of UVAG applicators, and the second was done after creating the treatment plan, just before the irradiation of first and third fraction. Both plans were compared in terms of changes of volumes and differences in the dose for high-risk organs using GEC-ESTRO Working Group parameters. RESULTS: The median planning time was 54 minutes (36-64 minutes). The absolute median change of volume for bladder, rectum, and sigmoid was 32.1 cm3 (1.6-108.6 cm3), 5.6 cm3 (0.4-61.8 cm3), and 8.4 cm3 (0.2-74.1 cm3), respectively. This difference led to an increased dose for bladder and sigmoid for D0.1cc by 46.7 cGy and 25.7 cGy, for D1cc by 59.2 cGy and 11.8 cGy, and for D2cc by 44.7 cGy and 10 cGy, respectively, per each fraction. Measured volume change in case of rectum led to a decreased dose per each fraction for D0.1cc with 7.1 cGy, for D1cc with 3.5 cGy, and for D2cc with 4.8 cGy. We observed that statistically significant dependency between the planning time and the dose was proved for rectum. The longer time for planning, the higher dose for rectum. The correlation coefficient for D0.1cc was 0.6715 (p = 0.0061), for D1cc was 0.6404 (p = 0.011), and for D2cc was 0.5891 (p = 0.0197). CONCLUSIONS: Extended treatment planning time for brachytherapy due to the changes in topography of small pelvis can lead to different dose in high-risk organs than previously planned. It seems that the most significant changes are related to rectum.

From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer.

Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized.

HILIC/ESI-MS determination of gangliosides and other polar lipid classes in renal cell carcinoma and surrounding normal tissues.

Negative-ion hydrophilic liquid chromatography-electrospray ionization mass spectrometry (HILIC/ESI-MS) method has been optimized for the quantitative analysis of ganglioside (GM3) and other polar lipid classes, such as sulfohexosylceramides (SulfoHexCer), sulfodihexosylceramides (SulfoHex2Cer), phosphatidylglycerols (PG), phosphatidylinositols (PI), lysophosphatidylinositols (LPI), and phosphatidylserines (PS). The method is fully validated for the quantitation of the studied lipids in kidney normal and tumor tissues of renal cell carcinoma (RCC) patients based on the lipid class separation and the coelution of lipid class internal standard with the species from the same lipid class. The raw data are semi-automatically processed using our software LipidQuant and statistically evaluated using multivariate data analysis (MDA) methods, which allows the complete differentiation of both groups with 100% specificity and sensitivity. In total, 21 GM3, 28 SulfoHexCer, 26 SulfoHex2Cer, 10 PG, 19 PI, 4 LPI, and 7 PS are determined in the aqueous phase of lipidomic extracts from kidney tumor tissue samples and surrounding normal tissue samples of 20 RCC patients. S-plots allow the identification of most upregulated (PI 40:5, PI 40:4, GM3 34:1, and GM3 42:2) and most downregulated (PI 32:0, PI 34:0, PS 36:4, and LPI 16:0) lipids, which are primarily responsible for the differentiation of tumor and normal groups. Another confirmation of most dysregulated lipids is performed by the calculation of fold changes together with T and p values to highlight their statistical significance. The comparison of HILIC/ESI-MS data and matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) data confirms that lipid dysregulation patterns are similar for both methods. Graphical abstract ᅟ.

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer.

The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome.

Stereotactic radiotherapy in the treatment of local recurrences of esophageal cancer.

Esophageal cancer (EC) consists of tumors with a generally poor prognosis, and treatment options for patients with disease recurrence are extremely limited. Due to this poor patient prognosis, the possible treatment toxicity should be carefully balanced against its potential benefit and patient quality of life. Stereotactic body radiotherapy (SBRT) is a rapidly expanding novel technique combining a short treatment time together with high local efficacy and an acceptable toxicity profile. There are no publications thus far presenting data regarding the usage of SBRT utilizing a conventional linear accelerator in locally recurrent EC patients. In the present study, 2 patients with recurrent EC in the neck lymph nodes were treated by SBRT in the Department of Oncology, University Hospital Olomouc, Czech Republic. The treatment dose was 30 and 40 Gy in 5 daily fractions, with a prescribed dose to 65 and 81% isodose, for each patient respectively, utilizing a volumetric arc therapy technique, a 6-MV photon beam and an Elekta Synergy linear accelerator. The treatment was delivered without any unintentional treatment interruptions and without any treatment-related acute toxicity. The maximum dose in the patients was 45.9 and 49.2 Gy, respectively. The maximum doses for the surrounding major blood vessels were 35.4 and 45.7 Gy, respectively. Maximum doses to the trachea and the esophagus in the first patient were 32.6 and 27.0 Gy. In the second patient, these doses were not clinically significant. SBRT utilizing linear accelerators should be considered in patients with localized recurrent EC, offering the patients the chance for local control with minimal treatment toxicity.

Potential Predictive Role of MicroRNAs in the Neoadjuvant Treatment of Esophageal Cancer.

Esophageal cancer is a disease with disappointing prognosis. Currently, there are no predictive factors that can identify patients who on the one hand would likely benefit from tri-modality management and, on the other hand, would not be significantly affected by the morbidity accompanying the treatment. MicroRNAs are short non-coding RNAs responsible for post-transcriptional modification of gene expression by binding to 3'-UTR of messenger RNA and represent emerging potential predictive biomarkers of treatment (chemotherapy and radiotherapy) efficacy and toxicity. We reviewed the current literature, addressing the potential predictive role of microRNAs for efficacy of chemotherapy (specifically cisplatin, 5-fluorouracil, doxorubicin and paclitaxel) and radiotherapy, including predicted targets in the cell. Altogether 82 articles were identified and included in this review. This may be the first review on this topic specifically focusing on neoadjuvant treatment of esophageal cancer.

[Current Status of Checkpoint Inhibitors in the Treatment of Esophageal and Gastric Tumors - Overview of Studies]. / Soucasné postavení checkpoint inhibitoru v lécbe nádoru jícnu a zaludku - prehled studií.

BACKGROUND: Despite recent advances in oncological treatment, gastric and esophageal cancer remain neoplastic diseases with poor prognoses. The only potential curative treatment is surgical resection with adjuvant or neoadjuvant chemotherapy/chemoradiotherapy. Targeted therapy of metastatic disease unfortunately does not provide better outcomes than for other tumor types, with the exception of trastuzumab and ramucirumab, which have relatively limited efficacy. Immunotherapy is a rapidly evolving treatment that has influenced the treatment guidelines for many tumors. In the present review, we summarize clinical trials of checkpoint inhibitors for the treatment of gastric and esophageal cancer, including published results and the perspectives of ongoing trials. RESULTS AND DISCUSSION: Gastric and esophageal cancer are tumors with high mutation loads that have attracted considerable attention since the beginning of interest in immunotherapy. Phase I clinical trials (Keynote 012, Javelin, KEYNOTE 028) have demonstrated efficacy and acceptable toxicity. These studies were followed by phase II clinical trials (KEYNOTE 059, CheckMate 032, JapicCTI-No.142422), which showed about a 10-30% overall tumor response rate and confirmed the predictive role of PD-L1 expression. Ongoing phase III clinical trials (CheckMate 648, KEYNOTE 181, KEYNOTE 590, CheckMate 577) should finally confirm whether checkpoint inhibitors have a role to play in a palliative and adjuvant setting. CONCLUSION: Checkpoint inhibitors are perspective treatment modalities for gastric and esophageal tumors.Key words: stomach neoplasms - esophageal neoplasms - immunotherapySubmitted: 19. 9. 2017Accepted: 22. 10. 2017 The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Prognostic Influence of Internal Mammary Node Drainage in Patients with Early-stage Breast Cancer.

BACKGROUND: The management of internal mammary nodes (IMNs) during multidisciplinary treatment of breast cancer has been debated for the last four decades without unequivocal conclusion. PATIENTS AND METHODS: We retrospectively reviewed patients with breast cancer who underwent sentinel lymph node biopsy at our center from 2008 until 2012. IMN drainage was assessed as a potential risk factor for local and distant disease recurrence. RESULTS: We identified 712 patients, with incidence of drainage to IMNs of 18.4%. No detrimental effect of the pattern of drainage to IMNs was found after a median follow-up of 58 months. A similar outcome was observed when drainage to IMNs was evaluated as a risk factor for patient survival. The potential risk factors for drainage to IMNs during sentinel lymph node biopsy were younger age (p=0.002) and tumor location in lower-outer, lower-inner, and upper-inner versus upper-outer quadrant (p<0.0001). CONCLUSION: The drainage to IMNs is unlikely to have a detrimental effect on patient outcome.

Treatment of brain metastases.

BACKGROUND: Brain metastases are a very common neurological sequela in cancer patients. The ability of current anti-cancer therapies to prolong overall survival is beleaguered by this development in the case of a number of different cancers. This review provides a general overview of relevant treatment modalities, highlights major decision strategies used in selecting the optimal treatment algorithm and summarizes important steps necessary before initiating therapy. METHODS: A PubMed database search was done to identify publications describing the treatment of brain metastases including surgery, radiotherapy and symptomatic care. RESULTS AND CONCLUSION: Patient performance status and extent of disease play the most important roles in selecting between an aggressive or more conservative approach. As several other options are available, treatment decisions should be made in cooperation with multiple medical specialties and the involvement of multidisciplinary teams. In the future, brain metastases could become less of a treatment obstacle than they are today.

Radiotherapy management of brain metastases using conventional linear accelerator.

BACKGROUND AND AIMS: As treatments for primary cancers continue to improve life expectancy, unfortunately, brain metastases also appear to be constantly increasing and life expectancy for patients with brain metastases is low. Longer survival and improved quality of life may be achieved using localised radiological and surgical approaches in addition to low dose corticosteroids. Stereotactic brain radiotherapy is one rapidly evolving localized radiation treatment. This article describes our experience with stereotactic radiotherapy using a linear accelerator. METHODS: We reviewed patients treated with stereotactic radiotherapy, from the time of its introduction into daily practice in our Department of Oncology in 2014. We collected the data on patient treatment and predicted survival based on prognostic indices and actual patient outcome. RESULTS: A total of 10 patients were treated by stereotactic radiotherapy, in one case in combination with whole brain radiotherapy and hippocampal sparing. There was no significant treatment related toxicity during the treatment or follow-up and due to the small number of fractions, the overall tolerance of the treatment was excellent. The patient intrafractional movement in all cases was under 1 mm suggesting that 1 mm margin around the CTV to create the PTV is sufficient and also that patient immobilization using the thermoplastic mask compared with invasive techniques, is feasible. We also found that prognostic indices such as the Graded Prognostic Assessment provide accurate predictions of patient survival. CONCLUSIONS: Based on our current evidence, patients with brain metastases fit enough, should be considered for stereotactic radiotherapy treatment.

Treatment of brain metastases of renal cell cancer with combined hypofractionated stereotactic radiotherapy and whole brain radiotherapy with hippocampal sparing.

Renal cell cancer patients with brain metastatic disease generally have poor prognosis. Treatment options include surgery, radiotherapy, targeted therapy or best supportive care with respect to disease burden, patient preference and performance status. In the present case report the radiotherapy technique combining whole brain radiotherapy with hippocampal sparing (hippocampal avoidance whole brain radiotherapy HA-WBRT) and hypofractionated stereotactic radiotherapy (SRT) of the brain metastases is performed in a patient with metastatic renal cell carcinoma. HA-WBRT was administered to 30 Gy in 10 fractions with sparing of the hippocampal structures and SRT of 21 Gy in 3 fractions to brain metastases which has preceded the HA-WBRT. Two single arc volumetric modulated arc radiotherapy (VMAT) plans were prepared using Monaco planning software. The HA-WBRT treatment plan achieved the following results: D2=33.91 Gy, D98=25.20 Gy, D100=14.18 Gy, D50=31.26 Gy. The homogeneity index was calculated as a deduction of the minimum dose in 2% and 98% of the planning target volume (PTV), divided by the minimum dose in 50% of the PTV. The maximum dose to the hippocampus was 17.50 Gy and mean dose was 11.59 Gy. The following doses to organs at risk (OAR) were achieved: Right opticus Dmax, 31.96 Gy; left opticus Dmax, 30.96 Gy; chiasma D max, 32,76 Gy. The volume of PTV for stereotactic radiotherapy was 3,736 cm3, with coverage D100=20.95 Gy and with only 0.11% of the PTV being irradiated to dose below the prescribed dose. HA-WBRT with SRT represents a feasible technique for radiotherapy of brain metastatic disease, however this technique is considerably demanding on departmental equipment and staff time/experience.