Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia.

The aim of the study was to conduct a retrospective database analysis to understand the current treatment patterns and outcomes to plan potential improvements in therapy delivery and patient selection. The electronic patient medical records of 225 patients with advanced gastric and esophagogastric adenocarcinoma treated at two Croatian high-volume tertiary centers from January 2018 to December 2021 were analyzed. Patients ineligible for chemotherapy (66 of 291, 22.7%) due to poor general condition or co-morbidities were not included in the study. The median overall survival (OS) for the whole cohort was 11.0 months (95% confidence interval (CI) 9.7-12.0). Of the 225 patients who received first-line therapy, 47.6%, 16.9%, and 3.1% received second-, third-, and fourth-line therapy, respectively. Survival correlated significantly with the number of treatment lines received (p<0.001), with a median OS from diagnosis of 7.8 (95% CI 6.6-9.4), 12.0 (95% CI 10.0-14.0), and 20.0 months (95% CI 18.0-23.0) for patients receiving 1, 2, and ≥3 lines of treatment, respectively. This study confirmed the positive impact of the number of chemotherapy lines on OS. This highlights the importance of the ratio of patients receiving multiple lines of therapy as well as the availability of new and effective drugs in real-life clinical practice. The selection of optimal therapy for each patient in the first-line therapy is important because a significant number of patients do not receive second-line therapy.

Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+).

Some sources report a connection of cellular senescence with chronic pathological conditions; however, the association between particular cellular processes and general health is rarely examined. This study aims to test the relationship of general health with DNA damage pathways that play a crucial role in senescence. The association of ten selected SNPs with subjective and objective general health and functional ability indicators has been tested in 314 oldest-old people from Croatia. Multivariate logistic regression was employed to simultaneously test the impact of variables potentially influencing targeted health and functional ability variables. The best model, explaining 37.1% of the variance, has six independent significant predictors of functional ability scores: rs16847897 in TERC, rs533984 in MRE11A, and rs4977756 in CDKN2B, chronic disease count, Mini-Mental State Examination scores, and age at surveying. In conclusion, the examined ten loci involved in DNA damage repair pathways showed a more significant association with self-rated health and functional ability than with the number of disease or prescribed medicaments. The more frequent, longevity-related homozygote (GG) in rs16847897 was associated with all three aspects of self-assessments-health, mobility, and independence-indicating that this TERC locus might have a true impact on the overall vitality of the oldest-old persons.

IMPACT OF CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY ON THE QUALITY OF LIFE IN CANCER PATIENTS.

The aim of the study was to investigate the correlation between chemotherapy-induced peripheral neuropathy (CIPN) and quality of life, as well as to establish whether there was a difference in peripheral neuropathy symptoms and their effect on the quality of life depending on the type of agents applied. The study encompassed 156 patients treated at the Department of Oncology from March to May 2017. Data were collected through self-reported questionnaires issued by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) and by Chemotherapy-Induced Peripheral Neuropathy module (CIPN20). The results showed sensory and motor neuropathy to be statistically significantly correlated with the general quality of life variables of pain, tiredness, diarrhea, insomnia and breathing difficulty. Oxaliplatin had a significantly greater effect on the onset of motor and sensory neuropathy than taxane and cisplatin/carboplatin. Nursing interventions based on specific characteristics of certain chemotherapeutic agents should be developed for CIPN alleviation.

THE MULTIDISCIPLINARY TEAM (MDT) IN THE TREATMENT OF HEAD AND NECK CANCER - A SINGLE-INSTITUTION EXPERIENCE.

Head and neck cancers are associated with significant morbidity and mortality despite advancements in treatment in recent decades. A multidisciplinary approach to the treatment of these diseases is thus of essential importance and is becoming the gold standard. Head and neck tumors also endanger relevant structures of the upper aerodigestive tracts, including bodily functions such as voice, speech, swallowing, and breathing. Damage to these functions can significantly influence quality of life. Thus, our study examined not only the roles of head and neck surgeons, oncologists and radiotherapists, but also the importance of the participation of different scientific professions such as anesthesiologists, psychologists, nutritionists, stomatologists, and speech therapists in the work of a multidisciplinary team (MDT). Their participation results in a significant improvement of patient quality of life. We also present our experiences in the organization and work of the MDT as part of the Center for Head and Neck Tumors of the Zagreb Clinical Hospital Center.

Environmental and behavioural head and neck cancer risk factors.

OBJECTIVES: The high incidence of head and neck cancer (HNC), significantly associated with living environment and behaviour, can be prevented more efficiently. The aim of this study was to evaluate the environmental and behavioural risk factors for HNC. METHODS: Using a detailed questionnaire on social status, education, living and occupational environment exposures, family cancer and lifestyle, HNC patients (103 cases, 76.7% of men) were compared with control subjects (244 subjects, 73% of men) balanced by age: mean (standard deviation) 63.8 (9.3) and 63.8 (9.0) for cases and controls, respectively. RESULTS: The results of this study showed that smoking and low education were significant risk factors for HNC regardless of sex. Family HNC and breast cancer were significant predictors of HNC risk. CONCLUSION: The study confirmed previous results that smoking and low education are significantly associated with HNC. Additionally, results pointed to significant HNC and breast cancer risk in HNC patient's families that may have originated from passive smoking or a smoking habit stemming from social environments that support it. Better dissemination programmes regarding smoking risks for children and adults are needed, targeting not only individuals but also families.

WHO SHOULD RECEIVE RADIOTHERAPY IN METASTATIC HORMONE-SENSITIVE PROSTATE CANCER?

The standard of treatment of metastatic hormone-sensitive prostate cancer (mHSPC) is androgen deprivation therapy (ADT) with docetaxel or abiraterone. However, numerous retrospective studies suggested outcome benefit of prostate radiotherapy. Small randomized trial (HORRAD) showed no overall survival (OS) benefit of the addition of prostate radiotherapy to ADT but there was a trend toward survival benefit in a low volume disease. Although the results of large randomized study (STAMPEDE) have also not proved improvement of OS in unselected patients, robust improvement of failure-free survival was found. In addition, OS was significantly improved in patients with a low volume disease. In the absence of reliable molecular markers, the extent of metastatic disease has emerged as an important factor for treatment decision making. In this review, we summarize data from non-randomized as well as from randomized studies concerning prostate radiotherapy to contribute to the improvement of treatment tailoring for each individual patient with mHSPC in order to achieve the best possible treatment outcomes.

Significance of stroma in biology of oral squamous cell carcinoma.

The worldwide annual incidence of oral squamous cell carcinoma (OSCC) is over 300,000 cases with a mortality rate of 48%. This cancer type accounts for 90% of all oral cancers, with the highest incidence in men over 50 years of age. A significantly increased risk of developing OSCC exists among smokers and people who consume alcohol daily. OSCC is an aggressive cancer that metastasizes rapidly. Despite the development of new therapies in the treatment of OSCC, no significant increase in 5-year survival has been recorded in the past decades. The latest research suggests focus should be put on examining tumor stroma activation within OSCC, as the stroma may contain cells that can produce signal molecules and a microenvironment crucial for the development of metastases. The aim of this review is to provide an insight into the factors that activate OSCC stroma and hence faciliate neoplastic progression. It is based on the currently available data on the role and interaction between metalloproteinases, cytokines, growth factors, hypoxia factor and extracellular adhesion proteins in the stroma of OSCC and neoplastic cells. Their interplay is additionally presented using the Systems Biology Graphical Notation in order to sublimate the collected knowledge and enable the more efficient recognition of possible new biomarkers in the diagnostics and follow-up of OSCC or in finding new therapeutic targets.

Comparison of intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and a 3-dimensional conformal parotid gland-sparing radiotherapy (ConPas 3D-CRT) in treatment of nasopharyngeal carcinoma: a mono-institutional experience.

AIM: To compare intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and a 3-dimensional conformal parotid gland-sparing radiotherapy (ConPas 3D-CRT) in treatment of nasopharyngeal carcinoma with regard to outcomes and dose distribution to the planning target volumes (PTVs) and to the organs at risk (OARs). METHODS: The treatment records of 24 patients with histologically proven carcinoma of the nasopharynx treated with ConPas 3D-CRT or IMRT-SIB technique between May 2009 and December 2016 were assessed. RESULTS: The mean dose and dose to 50% parotid glands volume as well as the maximal dose to the spinal cord were significantly lower in the IMRT-SIB than in the ConPas 3-CRT group (p < 0.05; p < 0.05; p < 0.01, respectively). IMRT-SIB was also superior in coverage of PTVs. The 3-year overall survival (OS) and disease-free survival (DFS) of patients in the IMRT-SIB and ConPas 3D-CRT groups were 77 and 81% (p = 0.93), 51.9 and 70.7% (p = 0.83), respectively. CONCLUSION: IMRT-SIB provided additional spearing to parotid glands and spinal cord in comparison to ConPas 3D-CRT technique but without improvement of OS and DFS.

A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma.

Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.

The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis.

Excision repair cross-complementation group 1 (ERCC1) protein has been extensively investigated as a prognostic and predictive factor for platinum-based treatment in head and neck squamous cell carcinoma (HNSCC) but with inconsistent results. We performed the present meta-analysis to better elucidate this issue in advanced HNSCC. A literature search was conducted using the PubMed and Web of Science databases. The inclusion criteria were head and neck cancer patients with platinum-based treatment and evaluation of the correlation between ERCC1 expression and clinical outcomes [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both unadjusted and adjusted estimates]. In high vs. low pooled analyses, high ERCC1 expression was associated with unfavorable OS [hazard ratio (HR) = 1.95, 95 % confidence interval (CI) 1.18-3.21, p = 0.009], PFS (HR = 2.39, 95 % CI 1.74-3.28, p = 0.000) and ORR (odds ratio = 0.48, 95 % CI 0.23-0.98, p = 0.044). In the subgroup analysis of adjusted OS estimates, ERCC1 was a predictor of shorter survival in Asians (HR = 3.13, 95 % CI 2.09-4.70, p = 0.000) and Caucasians (HR = 2.02, 95 % CI 1.32-3.07, p = 0.001) but of longer survival in South Americans (HR = 0.17, 95 % CI 0.07-0.40, p = 0.000). Immunohistochemistry proved to be of predictive value irrespective of used antibody (p = 0.009). In the stratified analysis according to the tumor site, ERCC1 expression was associated with OS in nasopharyngeal cancer (HR = 2.72, 95 % CI 1.79-4.13, p = 0.000). ERCC1 has a potential to become predictive and prognostic factor enabling treatment tailoring in HNSCC patients.

[CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH ESOPHAGEAL AND ESOPHAGOGASTRIC JUNCTION CANCERS].

Esophageal and esophagogastric junction cancers comprise histologically and biologically different malignant tumors in which the progress in the understanding of the disease has not been followed by the improvement in the survival. Diagnosis is set by tumor biopsy during endoscopy. Multimodal approaches containing surgery, radiotherapy and chemotherapy are frequently applied in the treatment of locoregionally advanced disease. However, the optimal sequence of the treatment options is still the issue of numerous clinical trials and meta-analyzes. Metastatic disease is treated with palliative chemotherapy and best supportive care. Treatment decisions should be individualized according to patients' characteristics and made after multidisciplinary team discussion. The following text presents the clinical guidelines in order to standardize the diagnostic procedures, treatment and monitoring of patients with esophageal and esophagogastric junction cancers in the Republic of Croatia.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with cancer of unknown primary site]. / Klinicke preporuke za dijagnozu, lijecenje i pracenje bolesnika oboljelih od raka nepoznata primarnog podrijetla.

Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia.

Sudden bilateral hearing loss in gastric cancer as the only symptom of disease.

This paper reports a case of sudden bilateral deafness as the first symptom of gastric cancer, an extremely rare and atypical clinical situation. Because common signs of stomach cancer were absent, the patient was first evaluated in the Department of Otolaryngology, University Hospital Center, Zagreb. Only after expanded diagnostic evaluation and rapid progression of the disease in such a case is a malignant tumor suspected. Treatment is mostly ineffective. The unusual presentation of the disease and the rapid course may indicate a hereditary predisposition. Inactivation of tumor suppressor gene DFNA5 was found in 50% of gastric cancers, but of a non-metastasized phenotype. Inactivated DFNA5, otherwise described in hereditary bilateral deafness, perhaps favors the development of deafness in patients with gastric cancer. Our patient had a positive multiple viral antibody titer in serum, inactivated DFNA5 in both gastric cancer tissues and cerebellar metastases, and a metastatic form of the disease. If sudden deafness occurs in elderly patients, the possibility of malignant tumor should be taken into consideration. The link between gastric cancer and the DFNA5 gene is unclear and requires further research.

Treatment of patients with anaplastic thyroid cancer during the last 20 years: whether any progress has been made?

Anaplastic thyroid cancer (ATC) is one of the most deadly cancers in humans. Searching a PubMed database, studies published during the last 20 years, 63 publications dealing with treatment of patients were identified. Cohort studies comprised 6,609 patients with the median age 68 years (range 57-77 years). The median survival was 3.9 months, and 1 year survival, 20%. The median survival of patients treated with multimodal therapy was 10.5 months. There was significant difference in median survival (7.0 vs. 3.8 months; p < 0.05) and 1 year survival (30.5 vs. 16.8 months; p < 0.05) between the patients <68 and 68 or more years old. Clinical trials, both randomized and non-randomized, comprised 205 patients. Unfortunately, considerable improvement in the understanding of the pathogenesis and genetics of the ATC has not yet resulted in the improvement of the outcome of these patients.

Fatal outcome of posterior "reversible" encephalopathy syndrome in metastatic colorectal carcinoma after irinotecan and fluoropyrimidine chemotherapy regimen.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity characterized by headaches, altered mental status, seizures, and visual disturbances. It can occur in many different clinical entities such as severe hypertension and pre-eclampsia, or due to cytotoxic or immunosuppressive therapies. The pathogenesis of PRES is unclear, with dysregulated cerebral auto-regulation and endothelial dysfunction as important mechanisms proposed. Endothelial dysfunction is important especially in cases associated with cytotoxic therapies. Herein, we describe a patient with PRES with fatal outcome, who presented 5 days after the infusion of cycle 1 of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) regimen chemotherapy, without prior hypertension and other comorbidity, suggesting a link between PRES and FOLFIRI regimen. To our knowledge, this case report is the first describing PRES after FOLFIRI regimen, although others have described PRES after FOLFIRI with bevacizumab in colonic cancer patients.

Prognostic value of ERCC1 in head and neck carcinoma treated with definitive or adjuvant radiotherapy.

PURPOSE: To evaluate the prognostic significance of excision repair cross-complementation group 1 (ERCC1) expression in head and neck carcinoma patients treated with definitive radiotherapy (DR) or adjuvant radiotherapy (AR). METHODS: ERCC1 expression was assessed by immunohistochemical staining. A total of 48 patients were assessed. RESULTS: High ERCC1 expression was found in 23 patients (48 %). More ERCC1-positive tumours were detected in patients treated with DR than in patients treated with AR (73 vs. 36 %, respectively, p = 0.03). ERCC1 expression had no impact on overall survival neither in the whole cohort of patients (p = 0.16) nor in each particular treatment group (AR p = 0.98; DR p = 0.21). CONCLUSIONS: ERCC1 expression had no predictive value in head and neck carcinoma patients treated with DR or AR. There might be difference in ERCC1 positivity that comes out of whether the assessment is done on biopsy or surgical specimens.

[Hormonal therapy of prostate cancer: are there any dilemmas left?]. / Hormonska terapija raka prostate: ima li jos dilema?

The strategy for treating prostate cancer patients depends on the assessment of disease extent, assessment of the risk of disease relapse, assessment of life expectancy, comorbidities, affinities and life-style. Since the activity and survival of prostate cancer cells is at least initially dependent on androgen stimulation, hormonal therapy is one of the several standard treatment modalities. Hormonal therapy is aimed at decreasing this androgen stimulation either by lowering androgen production or by blocking receptor binding. Hormonal therapy is in fact androgen-suppressive therapy (AST) or androgen-deprivation therapy (ADT). If effective, it results in the lack of cancer cell stimulation, thus causing their apoptosis and consequently decline in tumor growth and size. Hormonal therapy is used as a first-line treatment modality for metastatic disease. In addition to this indication, hormonal therapy is also used as an adjunct to radiotherapy with curative intent for patients with non-metastic disease but having an intermediate and high risk of disease relapse. In combination with radiotherapy, hormonal therapy can be applied before, concomitantly and after radiotherapy for the duration of 6 months or 2 to 3 years depending on the risk estimation. Regarding hormonal therapy, it can be applied in combination with other treatments, in several ways, and sometimes there might be several options available. This possible lack of a specific recommendation is a consequence of the fact that there is a limited number of adequate clinical studies which, moreover, may have yielded inconsistent results sometimes simply due to the patients' heterogeneity. Moreover, thanks to the newer and better diagnostic methods enabling the discovery of prostate cancer in earlier disease stages, as well as to the more effective treatments, there is also a prolongation of relapse-free survival and possibly of overall survival in patients having metastic disease. Consequently, the results of earlier clinical studies might no longer be applicable to the new "generations" of upcoming patients. As regards this improved survival, issues of patient's quality of life and possible side-effects of hormonal therapy are also becoming increasingly relevant because hormonal adverse events are time-dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, this paper aims to give an overview of the more recent findings, indications and observations regarding hormonal therapy.

Larynx preservation: advantages and limitations.

For a long time standard treatment approach for resectable squamous cell carcinoma of larynx was surgery with or without subsequent radiotherapy. Surgery, particulary total laryngectomy, has been associated with serious impairment of quallity of life. Between nonsurgical approaches, concurrent cisplatin based chemoradiotherapy has become a very promising treatment modality for larynx preservation. However, concurrent chemotherapy has been associated with serious toxicity. The most recent treatment approach in larynx preservation is related to taxan based induction chemotherapy.

A patient with prostate cancer and multiple myeloma-diagnostics and possible association of both diseases.

In this report, we describe a case of a patient with prostate cancer and multiple myeloma as the second metachronous malignant disease. To our knowledge, synchronous occurrence of bone marrow prostate cancer metastases and multiple myeloma-as it was found in the clinical disease course of our patient-has not been documented in the literature. Among other diagnostic procedures, cytomorphology and immunocytochemistry analyses contribute to detection of metastases of epithelial cells and synchronous plasma cell proliferation in bone marrow. Occurrence of multiple myeloma and prostate cancer in our patient adds to other similar reports and points to possible association between both diseases and also to other factors involved in the development of a second malignant disease. Further studies are needed to confirm and clarify this association, because prostate cancer is a relatively common malignant disease.

Side effects of adjuvant radiotherapy in men with testicular seminoma stage I.

In this study we followed up the side effects of adjuvant radiotherapy in patients with testicular seminoma stage I over a period from 13 to 84 months (median 28 months). The most frequent side effects during radiotherapy were gastrointestinal (nausea/vomiting), psychological, cognitive, and minor sexual problems.The reported side effects were treated by antiemetics and anxiolytics. After radiotherapy, the side effects persisted in 6 % of patients, but only a few of them required additional treatment. Healthy children were born to 76 % of patients in the 18 to 39 years age group. This study shows that adjuvant radiotherapy of the para-aortic lymph nodes with the total dosage of 24 Gy in 16 daily fractions administered to testicular seminoma patients causes acceptable side effects, does not adversely affect quality of life and fertility, if the approach to treatment is individual and family consulting is provided. This makes adjuvant radiotherapy of the para-aortic lymph nodes an acceptable treatment for testicular seminoma stage I patients.