Biomarkers of Trastuzumab-Induced Cardiac Toxicity in HER2- Positive Breast Cancer Patient Population.

Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

Adjuvant combined therapy with trastuzumab in patients with HER2­ positive breast cancer and cardiac alterations: implications for optimal cardio­oncology care.

INTRODUCTION: Recently, the prognosis of patients with HER2­positive breast cancer (BC) has improved significantly owing to the use of combined treatment modalities. However, systemic treatment is as-sociated with increased risk of cardiotoxicity. OBJECTIVES: We aimed to assess subclinical cardiac alterations during the final stage of adjuvant com-bined therapy, that is, trastuzumab therapy (TT), as potential predictors of late cardiac complications in patients with HER2­positive BC. PATIENTS AND METHODS: We enrolled 251 patients with HER2­positive BC treated with a radical local therapy, adjuvant chemotherapy (anthracyclines or anthracyclines + taxanes), and immunotherapy (trastuzumab). Patients underwent 6 echocardiographic examinations: at baseline, during TT, and after TT, with assessment of left ventricular ejection fraction (LVEF), degree of valvular regurgitation, and cardiac chamber diameters. RESULTS: Valvular fibrosis (28.4% of patients) was associated with older age, hypertension at baseline, and a higher degree of regurgitation during TT. Reduced LVEF, greater regurgitation, and larger cardiac chamber diameters were noted during TT. The patients who received higher anthracycline doses showed a greater degree of aortic insufficiency and a larger right ventricular diameter. Reduced LVEF during TT was associated with radiotherapy or chemotherapy and the degree of valvular regurgitation. Significantly larger diameters were observed in older patients and in those with comorbidities at baseline, high body mass index, and regurgitation. CONCLUSIONS: Asymptomatic subclinical cardiac alterations during TT may predict late cardiac complica-tions; however, longer follow­up is necessary to confirm this hypothesis. Patients with HER2­positive BC should be closely monitored for possible cardiac alterations during and after therapy to ensure optimal care and guide therapeutic decision­making.

Radiotherapy for brain metastases from small-cell lung cancer in distinct clinical indications and scenarios.

Management of brain metastases (BM) from small-cell lung cancer (SCLC) is complex and not supported by a strong evidence from prospective clinical trials. Owing to the different clinical and pathological characteristics of SCLC, patients with this histology were not included in the prospective studies on the value of whole-brain radiotherapy (WBRT) and local surgical or ablative radiation treatment like stereotactic radiosurgery (SRS). Chemotherapy also represents a major part of the armamentarium against BM from SCLC due to the well-recognized chemoresponsiveness of this cancer and the frequent presentation of BM with extracranial progression. WBRT in combination with chemotherapy has long been a standard approach in this setting. However, data on the neurocognitive toxicity and the lack of documented impact on overall survival of WBRT in the management of BM from other solid tumors, as well as the increasing availability of the stereotactic radiotherapy technologies, has led to the increasing use of SRS with omission of WBRT also in SCLC. In the current review the use of different modalities of radiotherapy and ways of combining radiotherapy with chemotherapy for BM from SCLC will be presented for distinct clinical situations: presentation of BM synchronous with primary, metachronous presentation of BM-without previous prophylactic cranial irradiation (PCI) vs. after PCI, and asymptomatic BM found at the staging before PCI.

WBRT for brain metastases from non-small cell lung cancer: for whom and when?-Contemporary point of view.

The incidence of brain metastases (BM) is estimated between 20% and 40% of patients with solid cancer. The most common cause of this failure is lung cancer, and in locally advanced non-small cell lung cancer (NSCLC) BM represent a common site of relapse in 30-55% cases. The basic criteria of therapeutic decision-making are based on the significant prognostic factors which are components of prognostic scores. The standard approach to treatment of BM from NSCLC include whole brain radiotherapy (WBRT) which is used as adjuvant modality after local therapy (surgery or stereotactic radiosurgery) or as primary treatment and it remains the primary modality of treatment for patients with multiple metastases. WBRT is also used in combination with systemic therapy. The aim of presented review of literature is trying to answer which patients with BM from NSCLC should receive WBRT and when it could be omitted. There were presented the aspects of application of WBRT in relation to (I) choice between WBRT or the best supportive care and (II) employment of WBRT in combination with local treatment modalities [surgical resection or stereotactic radio-surgery (SRS)] and/or with systemic therapy. According to data from literature we concluded that the most important factor that needs to be considered when assessing the suitability of a patient for WBRT is the patient's prognosis based on the Lung-molGPA score. WBRT should be applied in treatment of multiple BM from lung cancer in patients with favourable prognosis and in in patients with presence of EML4-ALK translocation before therapy with crizotinib. Whereas WBRT could be omitted in patients with poor prognosis and after primary SRS.

High Ki-67 expression is a marker of poor survival in apocrine breast carcinoma.

Apocrine carcinoma is a very rare type of breast cancer, which represents 0.5-4% of all breast cancers. The aim of the study was to analyze biological and clinical features of apocrine carcinoma and their influence on patients survival. The studied group consists of 57 patients, who underwent treatment between 1987 and 2010. Expression of ER, PgR, HER2, AR, GCDFP-15, EGFR, CK 5/6, CK 8/18 and Ki-67 was assessed immunohistochemically on formalin-fixed paraffin-embedded tissue sections. Presence of emboli and extent of lymphocyte infiltration were assessed on haematoxylin-eosin-stained slides. In the investigated group, 16 cases were ER/PgR positive and 49 were AR-positive. ER/PgR-negative tumours were often characterised by CK5/6 and EGFR positivity. The presence of AR was related to HER-2 and GCDFP-15 expression and tumours with expression of CK5/6 were more likely be EGFR positive and had higher Ki-67 LI. Higher probability of 10-years OS and DFS was observed in patients with tumours characterized by Ki-67 LI < 20% (p = 0.036 and p = 0.009, respectively). Favourable trend in OS was noted for patients with smaller tumours (p = 0.053), without lymph node metastases (p = 0.074) and without EGFR expression (p = 0.060). In apocrine breast carcinoma expression of Ki-67 is one of the most important factors influencing patients' survival.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Correlation between quantitative assessment of contrast enhancement in contrast-enhanced spectral mammography (CESM) and histopathology-preliminary results.

OBJECTIVES: Contrast-enhanced spectral mammography (CESM) is a novel method for breast cancer detection. The aim of this study is to check if there is a possibility of quantitative assessment of contrast enhancement in CESM and if there is any correlation between quantitative assessment of contrast enhancement in CESM and histopathology. METHODS: A total of 167 female patients underwent CESM. All subjects previously had suspicious lesions found on mammography, breast ultrasound, or both. After imaging, the following parameters were evaluated: number of enhancing lesions in each breast and size and degree of enhancement of each lesion. Based on the collected data, the percentage signal difference between enhancing lesion and background (%RS) and signal-difference-to-noise ratio (SDNR) were measured for each lesion. RESULTS: The number of lesions detected in the study population was 195. Among all diagnosed lesions, 120 (62%) were assessed to be infiltrating cancers, 16 (8%) non-infiltrating cancers, and 59 (30%) were benign. Thirteen (7%) lesions did not enhance in CESM; all non-enhancing lesions were confirmed to be benign under histopathological examination. Analysis of enhancement indices showed that signal values within lesions and signal values within background ROIs (regions of interest) were similar in CC (craniocaudal) and MLO (mediolateral) projections. Mean %RS values were correlated with the type of enhancing lesion, infiltrating cancers having the highest values, benign lesions the lowest. CONCLUSIONS: This work has demonstrated a significant correlation between the degree of lesion enhancement in CESM and malignancy. Quantitative analysis of enhancement levels in CESM can distinguish between invasive cancers and benign or in situ lesions. KEY POINTS: • There is a possibility of quantitative assessment of contrast enhancement in CESM. • Correlation between quantitative assessment of contrast enhancement in CESM and histopathology was observed.

Bilateral synchronous breast cancer developed as metachronous malignancy after therapy of other primaries.

OBJECTIVES: Cancer morbidity rates have been increasing steadily. A longer lifespan and easier access to modern diagnostic and therapeutic methods are the main reasons for the growing number of cancer survivors. Additionally, some types of oncological treatment, such as radiotherapy or immunosuppression, may also increase the risk of secondary tumors. These factors have resulted in an increased incidence of primary multiple cancers. Multiple primary cancers are generally under-stood as either synchronous, in which the cancers occur at the same time, or metachronous, in which the cancers follow in sequence (for instance, more than 2 months apart).The results published in other studies show that between 2% and 15.8% of all cancer patients have more primary multiple cancers. Within this group with multiple primary cancers, some have bilateral breast cancer, and our study focuses on patients from this group. MATERIAL AND METHODS: Our study describes 10 patients who were treated for bilateral synchronous breast cancer at the Cracow Branch of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology during the years 1992-2014 and who developed another primary tumor after their treatment bilateral synchronous breast cancer. RESULTS: In our discussion we present detailed data on the incidence of metachronous cancers in the 10 patients, including breast cancer, following the treatment of their other primary tumors. CONCLUSION: The 10 cases of our study, and clinical experiences and publications in general show how important it is for patients to continue medical follow-up after treatment of primary tumors, not only to detect recurrences as early as pos-sible, but also to diagnose any other malignancies occurring in other sites, including secondary, treatment-related tumors.

Radiotherapy alone as a method of treatment for sinonasal mucosal melanoma: A report based on six cases and a review of current opinion.

OBJECTIVES: Radiotherapy in patients with sinonasal mucosal melanoma (SNMM) was given as alternative treatment to surgery in cases with advanced, inoperable tumors or those not eligible for surgery. We presented the outcomes for patients with SNMM treated with radiotherapy alone. MATERIAL AND METHODS: The retrospective review of 6 consecutive SNMM (nasal cavity - 4 pts. and paranasal sinus - 2 pts.) patients (3 males and 3 females at mean age 64 years) treated between 2008 and 2016 was presented. The stage of disease was: T3 (1 pt.), T4a (3 pts.), T4b (2 pts.); with N0 and M0 in all patients. All patients underwent definitive primary photon radiotherapy (IMRT) alone; dose 66-72 Gy was delivered in 22-24 fractions given in 5 fractions (3 Gy) a week. RESULTS: The complete remission was observed in all our patients but only one patient survived 5 years without disease. Five patients died due to multiple distant metastases; two of those patients developed associated local recurrence 7-8 months after radiotherapy. CONCLUSION: SNMM has a poor prognosis due to its high metastatic potential. Based on our numerically small report and data from literature we concluded that primary radiotherapy alone assured complete remission and even 5-year disease-free survival in only a few individual patients.

Preoperative short-course radiotherapy in rectal cancer patients: results and prognostic factors.

OBJECTIVE: The purpose of this study was to evaluate the clinical outcome of preoperative short-course radiotherapy for rectal cancer patients. METHODS: The study group comprised 210 patients with pathologically proven resectable rectal cancer. Between 2001 and 2013, they were treated preoperatively with short-course radiotherapy (25 Gy delivered in five fractions), followed by total mesorectal excision. Adjuvant 5-fluorouracil-based chemotherapy was administered at the discretion of the treating physician, depending on the pathological stage. RESULTS: After a median follow-up of 57 months, the following 5-year survival rates were observed: overall survival-66.4%, disease-free survival-67.2%, locoregional relapse-free survival-91.7%, and distant metastases-free survival-71.5%. The local failure was observed in 15 patients. Ten patients (4.8%) achieved pathologic complete response. The multivariate analysis demonstrated the regional lymph node involvement to be statistically significant for unfavorable outcomes in terms of all estimated survival rates. Lymphovascular invasion was found to be a strong predictor of survival (HR = 1.68; 95% CI 1.29-3.55) and treatment failure (HR = 1.54; 95% CI 1.08-3.34). The presence of positive surgical circumferential margin was related to six times higher risk of locoregional recurrence. Early and late severe treatment-induced toxicity was reported in 1 and 7.6% patients, respectively. CONCLUSIONS: Preoperative short-course radiotherapy followed by total mesorectal excision and adjuvant chemotherapy allows to achieve excellent local control and favorable survival rates. The treatment-induced toxicity is acceptable.

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs.

Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report.

BACKGROUND/AIM: It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. MATERIALS AND METHODS: For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern - as homogenous and heterogenous. RESULTS: Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). CONCLUSION: Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information.

Prognostic role of lymphatic vessel density and lymphovascular invasion in chemotherapy-naive and chemotherapy-treated patients with invasive breast cancer.

It is assumed that the spread of breast cancer cells via the lymphatic system might be influenced by inflammatory reactions and/or the application of chemotherapy or molecularly targeted therapy. Therefore, we analysed survival according to lymphatic vessel density (LVD), lymphovascular invasion (LVI) (both assessed using podoplanin as immunohistochemical marker of lymphatic endothelium) and well-established clinico-pathological features in a group of 358 patients with invasive ductal breast cancer: 139 chemotherapy-naïve (pT1-2/pN0/M0) and 219 treated with chemotherapy (pT1-4/pN1-3/M0). Univariate analysis revealed that high LVD was related to unfavourable disease-free survival (DFS) in pN0/chemotherapy/trastuzumab-naïve patients (P = 0.028). Conversely, in pN+/chemotherapy-treated individuals high LVD was related to favourable DFS (P = 0.019). LVI was a significant indicator of survival (P = 0.005) only in pN0/chemotherapy/trastuzumab-naïve patients. The following parameters were significant independent adverse prognostic factors for DFS: (i) in pN0/chemotherapy/trastuzumab-naïve patients: high LVD (LVD > 7 vessels/mm2; RR = 2.7, P = 0.039), LVI (RR = 3.3, P = 0.046) and high tumor grade (G3 vs. G1 + G2; RR = 2.6, P = 0.030); (ii) in pN+/chemotherapy/trastuzumab-treated patients: low LVD (RR = 1.8, P = 0.042), the number of involved lymph nodes (pN3 vs. pN1-2; RR = 2.3, P = 0.012) and the breast cancer subtype (expression of steroid receptors together with HER2 immunonegativity and high proliferation index vs. other breast cancer immunophenotypes; RR = 3.0, P < 0.001). High LVD may identify high progression risk in pN0/chemotherapy/trastuzumab-naïve patients, and low progression risk in pN+/chemotherapy-treated patients. This phenomenon might be explained by potential involvement of lymphangiogenesis in two processes related to cancer eradication: a chemotherapy-stimulated activity of the immune system against cancer cells, or increased tumour drainage influencing the efficacy of cytotoxic drugs.

Analysis of risk factors for pulmonary complications in patients with limited-stage small cell lung cancer : A single-centre retrospective study.

INTRODUCTION: The most effective therapy in patients with limited-stage small cell lung cancer (LS SCLC) seems to be chemotherapy (using platinum-based regimens) and thoracic radiotherapy (TRT), which is followed by prophylactic cranial irradiation. MATERIALS AND METHODS: The analysed group comprised 217 patients who received combined treatment for LS SCLC, i.e. chemotherapy (according to cisplatin and etoposide schedule) and TRT (concurrent in 101 and sequential in 116 patients). The influence of chemoradiotherapy (ChT-RT) schedule on treatment results (frequency of complete response, survival rates, and incidence of treatment failure and complications) was evaluated, and the frequency and severity of pulmonary complications were analysed to identify risk factors. RESULTS: The 5­year survival rates in concurrent vs. sequential ChT-RT schedules were 27.3 vs. 11.7% (overall) and 28 vs. 14.3% (disease-free). The frequencies of adverse events in relation to concurrent vs. sequential therapy were 85.1 vs. 9.5% (haematological complications) and 58.4 vs. 38.8% (pulmonary fibrosis), respectively. It was found that concurrent ChT-RT (hazard ratio, HR 2.75), a total dose equal to or more than 54 Gy (HR 2.55), the presence of haematological complications (HR 1.89) and a lung volume receiving a dose equal to or greater than 20 Gy exceeding 31% (HR 1.06) were the risk factors for pulmonary complications. CONCLUSION: Pulmonary complications after ChT-RT developed in 82% of patients treated for LS SCLC. In comparison to the sequential approach, concurrent ChT-RT had a positive effect on treatment outcome. However, this is a factor that can impair treatment tolerance, which manifests in the appearance of side effects.

Degree of Enhancement on Contrast Enhanced Spectral Mammography (CESM) and Lesion Type on Mammography (MG): Comparison Based on Histological Results.

BACKGROUND Contrast enhanced spectral mammography (CESM) is a new method of breast cancer diagnosis in which an iodinated contrast agent is injected and dual-energy mammography is obtained in multiple views of the breasts. The aim of this study was to compare the degree of enhancement on CESM with lesion characteristics on mammography (MG) and lesion histology in women with suspicious breast lesions. MATERIAL AND METHODS The degree of enhancement on CESM (absent, weak, medium, or strong) was compared to lesion characteristics on MG (mass, mass with microcalcifications, or microcalcifications alone) and histology (infiltrating carcinoma, intraductal carcinoma, or benign) to compare sensitivity of the two modalities and to establish correlations that might improve diagnostic accuracy. RESULTS Among 225 lesions identified with CESM and MG, histological evaluation revealed 143 carcinomas (127 infiltrating, 16 intraductal) and 82 benign lesions. This is the largest cohort investigated with CESM to date. The sensitivity of CESM was higher than that of MG (100% and 90%, respectively, p=0.010). Medium or strong enhancement on CESM and the presence of a mass on MG was the most likely indictor of malignancy (55.1% p=0.002). Among benign lesions, 60% presented as enhancement on CESM (were false-positive), and most frequently as medium or weak enhancement, together with a mass on MG (53%, p=0.047). Unfortunately, the study did not find combinations of MG findings and CESM enhancement patterns that would be helpful in defining false-positive lesions. We observed systematic overestimation of maximum lesion diameter on CESM compared to histology (mean difference: 2.29 mm). CONCLUSIONS Strong or medium enhancement on CESM and mass or mass with microcalcifications on MG were strong indicators of malignant transformation. However, we found no combination of MG and CESM characteristics helpful in defining false-positive lesions.

Pure and Mixed Mucinous Carcinoma of the Breast: A Comparison of Clinical Outcomes and Treatment Results.

Mucinous breast carcinoma (MBC) carcinoma represents approximately 1-6% of all malignant breast carcinoma and is divided into pure (PMBC) and mixed (MMBC) subtypes. This study presents the comparison of clinical characteristics and treatment results in 70 patients with PMBC and 40 patients with MMBC, treated at a single institution during 25 years. Performed analyses showed that only nodal status was different in both subtypes. Patients with MMBC showed a significantly higher incidence of axillary nodal metastases in comparison to PMBC (25% versus 10%, respectively). Instead, the 10-year disease-free survival rate was significant higher in PMBC than MMBC (85.7% versus 65%, p < 0.02, test log rank). Authors own observations and data from literature proved that MMBC should be considered as subtypes of mucinous breast cancer.

Human Epididymis Protein 4 (HE4) in Patients with Small-Cell Lung Cancer.

BACKGROUND: The aim of the present study was to compare the diagnostic utility of HE4 with NSE, ProGRP, CYFRA 21-1, CEA, and CA 125 and evaluate their prognostic value in patients with small-cell lung cancer (SCLC). METHODS: HE4, ProGRP, NSE, CYFRA 21-1, CEA, and CA 125 assays were performed in 63 patients with smallcell lung cancer (limited disease (LD) - 41, extensive disease (ED) - 22) and in 66 individuals of the reference group. RESULTS: Area under the ROC curves for HE4, ProGRP, NSE, CA 125, CYFRA 21-1, and CEA were 0.884, 0.923, 0.826, 0.796, 0.739, and 0.704, respectively. The tumor marker serum concentrations were associated with tumor stage (HE4, ProGRP, NSE, CYFRA 21-1, CEA), and disease progression occurred within one year (HE4, ProGRP, NSE, CYFRA 21-1). The tumor advancement, performance status, gender and tumor markers, except CEA and CA 125, were significantly associated with survival. Independent, unfavourable prognostic factors included extensive disease (HR 4.14, p < 0.0001) and NSE concentration above 35 g/l (HR 2.62, p = 0.0009). CONCLUSIONS: Diagnostic utility of HE4 was similar to that of NSE and ProGRP. Complementary to NSE, determination of HE4 seems to be helpful in evaluation of SCLC patients' prognosis.

Evaluation of intraocular proton beam irradiation complications after choroidal melanoma treatment. / [Ocena wewnatrzgalkowych powiklan po terapii protonowej czerniaków naczyniówki].

Purpose: The aim of the research was to evaluate of intraocular complications after proton beam therapy of choroidal melanomas Material and methods: A total 105 patients (48 female and 57 male) from Department of Ophthalmology and Ocular Oncology of University Hospital in Cracow, who received proton beam radiation due to choroidal melanoma were enrolled. The mean age was 52.3 years (51.8 y. in females, 52.6 y. in males). Total irradiation dose was 60 cGy and it was applied in 4 fractions per 15 cGy (on 4 consecutive days). We evaluated the incidence of complications classifying patients by age, tumor location, tumor thickness, longitudinal and transversal basal diameter and follow-up period, which ranged between 5 and 57 months. Results: Complications of intraocular irradiation were observed in 33 out of 105 treated patients. Retinopathy occurred in 18 cases, including 4 patients with macular edema. Neuropathy was confirmed in 8 patients, secondary glaucoma in 6 cases; we noted 9 cases of initial or progress existing cataract, 4 cases of dry eye syndrome and 1 patient with central retinal vein occlusion. A statistically significant positive correlation was demonstrated between the length of the follow-up period and the incidence of complications, which were more common and more severe with the longer follow-up period. There was no statistically significant correlation between the incidence of complications and patient's age, tumor location, tumor thickness as well as longitudinal and transversal basal diameter. Conclusion: All forms of radiation therapy used in intraocular tumors are associated with some risk of complications; proton beam radiotherapy is not free of that risk, either.