Corrigendum: Systemic treatment of breast cancer. 1st Central-Eastern European professional Consensus Statement on breast cancer.

[This corrects the article DOI: 10.3389/pore.2022.1610383.].

Factors affecting prognosis in patients treated with bevacizumab plus paclitaxel as first-line chemotherapy for HER2-negative metastatic breast cancer: an international pooled analysis of individual patient data from four prospective observational studies.

BACKGROUND: Bevacizumab (BV) plus paclitaxel (PTX) is a treatment option in patients with HER2-negative metastatic breast cancer (mBC). We conducted an international pooled analysis with individual patient data to evaluate the effectiveness of BV + PTX as a first-line treatment for HER2-negative mBC patients under routine practice. METHODS: A total of 2,474 mBC patients treated with BV + PTX from four prospective observational studies were analyzed. The primary endpoint was overall survival (OS). The other endpoints including identifying independent prognostic factors and validation of the modified Prognostic Factor Index (PFI) developed in the ATHENA trial. RESULTS: Median follow-up time was 10.9 months (M). Median OS were 21.4 M (95% confidential interval 19.8-22.7 M). The seven independent prognostic factors (tumor subtype, age, ECOG performance status (PS), disease-free interval (DFI), liver metastases, number of metastatic organs, and prior anthracycline and/or taxane treatment) for OS found in this analysis included the five risk factors (RFs [DFI < 24 months, ECOG PS 2, liver metastases and/or > 3 metastasis organ sites, TNBC, prior anthracycline and/or taxane therapy]). High- (> 3 RFs [median OS 12.6 M]) and intermediate-risk groups (2 RFs [median OS 18.0 M]) had a significantly worse prognosis than the low-risk group (< 1 RF [median OS 27.4 M]), (p < 0.0001). CONCLUSIONS: This international pooled analysis showed the effectiveness of first-line BV + PTX for HER2-negative mBC patients identifying seven independent prognostic factors as real-world evidence. The usefulness of the modified PFI developed in the ATHENA trial in predicting OS among patients receiving BV + PTX was also verified.

Oncodiabetology III. The relationship of antineoplastic therapies and carbohydrate metabolism / Onkodiabetológia III. Az antineoplasztikus terápiák és a szénhidrát-anyagcsere viszonya

The epidemiological indicators of malignant diseases and diabetes are changing similarly, as lately both have been dynamically increasing worldwide. They occur usually in the same patient synchronously or metachronously, because of their common metabolic and molecular background. Consequently, in more and more cases they require common treatment. That has led to a new science, called oncodiabetology, the main purpose of which is to optimize the combination of antineoplastic and antidiabetic therapies. Regarding the antineoplastic agents, their complex influence on metabolism has to be considered, especially diabetogenic side effects inducing insulin-resistance and decreasing insulin production. According to antidiabetic agents' role in preventing tumors, diminishing toxicity of cytostatic drugs, and promoting the breakthrough of chemoresistance should be considered. In this study, we investigate the contexts of antineoplastic agents' efficiency and the glucometabolism of the organization, the characteristics of oncotherapy in patients suffering from malignant disease and diabetes, and review those cytostatic agents, having massive diabetogenic adverse effects. We describe the properties and subtypes of secondary diabetes, thoroughly discuss the specific characteristics of hyperglycaemia and diabetes caused by malignant diseases and antineoplastic treatments, especially pancreatic diabetes. In the end, we attempt to determine the proper place and role of oncodiabetology in the treatment of patients suffering from malignancies. During our investigation, we assessed the effects on glucometabolism of the recently used classic cytostatics, molecularly targeted therapies and different endocrine manipulations treating malignancies. We reviewed the schedules and scientific background of almost 300 medicines for this aim. We established that every third antineoplastic agent influenced glucometabolism adversely. We report our further observations in our next reviews.

Systemic Treatment of Breast Cancer. 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified based on the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The professional guideline primarily reflects the resolutions and recommendations of the current ESMO, NCCN and ABC5, as well as that of the St. Gallen Consensus Conference statements. The recommendations cover classical prognostic factors and certain multigene tests, which play an important role in therapeutic decision-making. From a didactic point of view, the text first addresses early and then locally advanced breast cancer, followed by locoregionally recurrent and metastatic breast cancer. Within these, we discuss each group according to the available therapeutic options. At the end of the recommendations, we summarize the criteria for treatment in certain rare clinical situations.

[Rare, but existing clinical entity - the neuroendocrine cancer of the bladder]. / Ritka, de létezo entitás ­ a húgyhólyag neuroendokrin rákja.

The neuoroendocrine cancer of the bladder is a rare tumor, and from this entity the well-differentiated tumors with favorable prognosis, the paraganglioma with unfavorable prognosis, small and large cell types of tumors should be emphasized. From the methods of the anticancer therapies operation can be eligible by itself in the first group but in the second group should form only the part of the multimodal treatment. Radiotherapy plays a role only in the treatment of the small and large cell tumors and during the treatment of these tumors the administration of the cytostatic drugs is also essential (mainly platina derivates). Somatostatin analogs, immune checkpoint inhibitors could be beneficial in special cases and some tumor agnostic treatment can be useful as well. Moreover, the palliative treatment should represent an important modality even in the early treatment period but it should also be provided when no other treatment options are left.

["The phlebotomist" - venous punction and venous access obtaining in the department of oncology]. / A "vérvételes" ­ vénapunkció és -biztosítás onkológiai centrumunkban.

The protection of the veins in patients with malignancies is of high importance (regarding both blood taking and the drug administration). In order to prevent any unnecessary injury, every phlebotomy needs to have a sophisticated indication and requires skilled hands and adequate mentality. For the administration of cytostatic treatment, insertion of cannula is necessary, in most of the cases through a peripheral vein. Recently with more successful treatment possibilities, patients undergo many subsequent types of treatment. Thus, more examinations and diagnostic procedures (e.g. blood taking, radiologic examinations) are needed. Therefore, the need for central venous catheter or Porth-a-Cath device is increasing. Our report demonstrates general guidelines of blood taking and our everyday practice.

[Systemic treatment of breast cancer: professional guideline]. / Az emlorák szisztémás kezelése: szakmai irányelvek.

Since the III. Breast Cancer Consensus Conference, a number of new evidence based on clinical trial results have been published which justified updating the 2016 recommendation. In addition to classical prognostic factors, some multigenic tests, which we have incorporated into the recommendation, will play an important role in therapeutic decision-making. The professional guide primarily reflects the resolutions and recommendations of the current ESMO, NCCN, ABC4, as well as the St. Gallen Consensus Conference. From a didactic point of view, the text follows first the line of early and then locally advanced breast cancer, locoregionally recurrent and metastatic breast cancer. Within these, we discuss each group according to therapeutic options.

[Systemic therapy of breast cancer: practice guideline]. / Az emlõrák szisztémás kezelése: szakmai útmutatás.

The article presents the practice guideline of systemic treatment of breast cancer and recommendations of the 3rd Hungarian Breast Cancer Consensus Conference. It reflects the recent international guidelines (ESMO, NCCN, ABC2, St Gallen's) irrespectively of the current financial opportunities. Here we follow the early - locally advanced - locally relapsed - metastatic breast cancer line for didactic considerations and we discuss the different subgroups of breast cancer based on hormone receptor and HER2 receptor status. Diagnosis and treatment options of rare clinical entities are summarised at the end of the paper.

Prospective noninterventional study on the use of panitumumab monotherapy in patients with recurrent or progressive colorectal cancer: the VECTIS study.

PURPOSE: Epidermal growth factor receptor-targeted monoclonal antibodies are active as monotherapy beyond second-line treatment. Skin toxicities (STs) are common during treatment, and a positive association between ST severity and patient outcome has been reported. This study collected information on panitumumab monotherapy use in patients with KRAS exon 2 wild-type metastatic colorectal cancer in clinical practice. METHODS: This open-label, prospective, observational, noninterventional study included adult patients who had failed prior chemotherapy with 5-fluorouracil, oxaliplatin, and irinotecan. Patients received panitumumab monotherapy (6 mg/kg every 2 weeks) for ≤18 cycles. Effectiveness was assessed as disease control rate (DCR), tumor response, and freedom from progression. The incidence of ST and other adverse drug reactions (ADRs) was recorded, as were Eastern Cooperative Oncology Group performance status (ECOG PS) and quality of life. The KRAS analysis process was also evaluated. FINDINGS: The full analysis set included 632 patients (64.6% male; mean age, 62.3 years), who completed a mean of 9.6 panitumumab cycles. ST, mainly grade 1/2, occurred in 84.3% of patients, 82.7% of whom required treatment. Nonskin ADRs occurred in 3.5% of patients. By the end of treatment, the DCR was 58.9% overall, and was 53.8% and 62.7%, respectively in patients with ST grade 0/1 and grade 2/3. Significant associations were observed between maximum ST grade and best response (P=0.0009), DCR (P=0.0046), tumor response (P=0.0002), and freedom from progression (P=0.0084). At the end of the study, 67.4% of the patients had an ECOG PS of 0/1. Quality of life was rated as "very good" or "good" in 70.3% of patients. Mean time to obtain KRAS results was 18.2 days; satisfaction with different aspects of KRAS testing was "very good" or "good" in 80%-97% of patients. CONCLUSION: Panitumumab monotherapy showed adequate effectiveness and safety in patients with heavily pretreated KRAS exon 2 wild-type metastatic colorectal cancer. The most common ADR was grade 1/2 ST.

[Fulvestrant (Faslodex®) for hormone sensitive breast cancer. A review]. / Fulvestrant (Faslodex®) hormonérzékeny emlorákban. Áttekintés.

Endocrine agents are well established standards of care in hormone-sensitive postmenopausal breast cancer. The pure estrogen receptor antagonist (down-regulator) fulvestrant after binding to the ER induces its conformational change which disrupts ER signal and accelerates ER degradation. Fulvestrant is devoid of partial agonist activity. In unselected patients there was no difference in TTP between "standard dose" fulvestrant and aromatase inhibitors, but in first-line treatment of advanced breast cancer the elevated dose of fulvestrant may delay progression and may extend the overall survival compared with aromatase inhibitors.

First-line bevacizumab-paclitaxel in 220 patients with metastatic breast cancer: results from the AVAREG study.

BACKGROUND: First-line bevacizumab-paclitaxel therapy demonstrated a median progression-free survival (PFS) of 11 months in three randomized phase III trials on metastatic breast cancer (mBC) (E2100, TURANDOT and CALGB 40502). We assessed the efficacy and safety of bevacizumab-paclitaxel in a routine oncology practice study. PATIENTS AND METHODS: Patients with previously untreated mBC received bevacizumab-paclitaxel according to the approved indication in Hungary. The primary end-point was PFS. Secondary end-points included time-to-treatment discontinuation, 1-year survival rate, PFS in patients with triple-negative breast cancer (TNBC) and safety. RESULTS: Median PFS in the 220 treated patients was 9.3 (95%CI 7.8-10.8) months. The 1-year survival rate was 68%. In patients with TNBC (N=106), median PFS was 8.3 months (95%CI 7.8-8.8). Adverse events were consistent with the established safety profile of bevacizumab-paclitaxel. CONCLUSION: Bevacizumab-paclitaxel is an active and well-tolerated first-line treatment for mBC, with notable activity in TNBC.

[Gastrointestinal locations of primary melanoma]. / A primer melanoma malignum ritka gastrointestinalis lokalizációi.

Primary gastrointestinal melanomas, part of the mucosal melanoma group, are uncommon. They constitute about five percent of all melanomas and most of them are located in the rectum (3 percent of all melanomas). The prognosis is poor, overall 5-year survival in rectal melanoma is 10-20 percent. We present three of our cases. The first case - a 68-year-old male patient - was operated on for histologically proved rectal melanoma. Three years after radical excision and oncological treatment a metastasis of the primary tumor was diagnosed in the stomach. Total gastrectomy was performed, followed by oncological treatment. In the second case of a 59-year-old male patient an appendectomy was performed for symptoms of appendicitis. The histopathological examination revealed melanoma of the appendix. Further investigations revealed the primary tumor in the stomach and metastases in the lungs as well. The third case - an 82-year-old female patient - was investigated for frequent defecations, mucus in stool and fecal incontinence. Primary melanoma was proved in the lower third of the rectum with multiple hepatic metastases. These three cases in our practice are remarkable for the rarity of the disease, and in two cases the presence of both the primary tumor and the metastasis were located in the gastrointestinal tract.

[Use of angioneogenesis inhibitor monoclonal antibody following standard therapy in recurrent or progressive glioblastoma multiforme]. / Érújdonképzodés-gátló monoklonális antitest alkalmazása a szokásos kezelést követoen kiújuló vagy progrediáló glioblastoma multiforme kezelésében.

Glioblastoma is a brain tumor with poor prognosis in the therapy of which operation, postoperative temozolomide sensitized radiochemotherapy followed by temozolomide monotherapy offer the best chances. Administration of temozolomide is also recommended in relapse if the patient is naïve to this treatment. In recurrent or progressive glioblastoma following the above therapy, several biological therapeutic agents were tested, out of which the angiogenesis inhibitor bevacizumab has been approved by FDA (and similar authority of several other countries). Bevacizumab monotherapy resulted in objective tumor response in 28.2%, the median of progression-free survival was 4.2 (2.9-5.8) months, the median of overall survival was 9.2 (8.2-10.7) months. When combined with irinotecan, these results were 37.8%, 5.6 (4.4-6.2) and 8.7 (7.8-10.9) months, respectively. Adverse events were known from the use of bevacizumab in other indications, symptoms affecting the central nervous system were mild, i.e. the therapy proved to be not only effective but safe as well. Reduction of edema provided further advantage. In Hungary the product is available for "off-label" use only through a fairness request process.

[Detection of multiple colon and rectal tumors during diagnostic treatment and follow-up]. / Többszörös vastag- és végbéldaganatok felismerése a kivizsgálás, kezelés és gondozás során.

Recognition of the commonly encountered colorectal cancer (CRC) generally begins and takes place because of and based on symptoms and signs, due to the unsettled screening of this type of cancer. Sometimes, because of advanced stage cancer urgent surgical intervention could become necessary and, if this is the case, there is no time and possibility for searching for an eventual second tumor and perhaps the patient's status does not permit performing intraoperative investigations either. The incidence of multiple colon cancer is considered to be between 2.5 and 30% according to the literature. That is why one should exclude them even in the absence of pre- and intraoperative investigations and complaints. On the other hand, colonoscopy and perhaps irrigoscopy of seemingly healthy followed-up patients is mandatory. In the case of the presence of complaints/symptoms denoting impaired intestinal passage seen in a followed-up patient or during the adjuvant setting or metastatic/recurrent disease, treatment and even during hospice care we should evaluate the possibility of a second metachronous tumor. Moreover, if there is no urgency, the multidisciplinary team (oncoteam) should recommend the adequate treatment by balancing gain/utility and risk.

[Thoughts about thromboembolic events prophylaxis in cancer patients]. / Gondolatok a daganatos betegek vénás trombózisprofilaxisáról.

The risk of venous thromboembolic events (VTE) in cancer patients is higher than in the general population. Treatment may also increase this risk in these patients. Based on the appropriate criteria (of which the most important are the current ministerial guidelines) thrombosis prophylaxis should be started (given that there is no contraindication) on these patients and be continued while they are at risk. In the event of permanent risk thrombosis prophylaxis should be given lifelong. The drug of choice is low-molecular-weight heparin (LMWH) which is safer and more effective than the oral vitamin K antagonists. Platelet aggregation inhibitors have proved unsuccessful in this patient group. The evidence so far suggests that LMWH (during VTE prophylaxis) can have a positive impact on the course of cancer and perhaps it will be registered under the indication section for cancer patients in the future.

[Extravasation of cytostatic drugs]. / Citosztatikumok paravazációja.

Paravasation of cytostatic drugs during peripheral intravenous administration is a well known complication. In the United States of America it occurs in seven percent of cases with different severity and consequences. Although methods to completely avoid this complication are still unavailable, we are able to decrease the risks by identifying the patient- and procedure-related factors. The educated patient is a good indicator of paravasation in case he or she can cooperate and call the nurse. When the patient is unable to cooperate, the risks of extravasation is higher and closer nursing surveillance is indicated. The extent of injury depends mainly on the chemical structure of the extravasant substance (vesicant, irritant or non-vesicant) which may be modified by other factors. There is no strong evidence-based guidance for the management of complication. Abrupt cessation of the infusion and drawing back on the inserted venous catheter as well as elevating and resting the affected limb are necessary measures. In the available literature cooling or warming of the affected area is controversial. Similarly there are still open questions regarding the value of using antidotes as dexrazoxane, dimethylsulfoxide, thiosulfate and hyaluronidase (which is not registered as medicament in Hungary). In the event of extravasation early multidisciplinary dermatological and surgical assessment is essential for definitive diagnosis and setting the optimal management.

[Antidiabetic therapy--a new possibility in the complex therapy of cancer?]. / Antidiabetikus kezelés, mint újabb lehetoség a daganatok komplex terápiájában.

Nowadays the lack of exercise and improper eating habits are main characteristics of modern life style. This favors not only formation of type 2 diabetes or cardiovascular diseases, but also increaseas the incidence and prevalence of malignant tumors. Today there are many epidemiologic trials that demonstrate the connection between type 2 diabetes and formation of several malignomas. Its cause should be searched in common paths of pathologic processes. One of this is the birth of hyperinsulinsulinemia, which accompanies insulin resistance. Hyperinsulinemia of the host leads to increased glucose uptake in the highly insuline sensitive tumor cells which supports tumor growth. This makes type 2 diabetes a metabolic state favoring tumor formation, suggesting a potential application of oral insulin sensitizers in cancer therapy. Currently several international trials are testing the anti-tumor activity of metformin and thiazolidinedions (TZD). Besides this, encouraging results were obtained with the use of anti-IGFR antibodies in the treatment of tumors. A common therapy of diabetes and tumor may lead to new possibilities in the treatment of malignant tumor diseases. By doing this we could be able to weaken the tumor and strengthen the body, enabling it to fight against cancer. Bánhegyi RJ, Rus-Gal PO, Nagy AK, Martyin T, Varga R, Pikó B. Correlation between type 2 diabetes and malignant tumors - new possibilities in the complex therapy of cancers?

[Panitumumab-treatment of metastatic colorectal cancer]. / Panitumumab alkalmazása az áttétes vastag- és végbélrákos betegek kezelésében.

In the molecular target treatment strategy of metastatic colorectal cancer patients panitumumab represents a new class of drugs due to its fully human nature, and no need for premedication and loading dose. Panitumumab binds to epidermal growth factor receptor (EGFR) selectively. In registration pivotal studies the analysis of patient subgroups for KRAS status gives strong evidence for the important role of RAS oncogene: median progression-free survival was 16 weeks on panitumumab arm in KRAS wild-type patients (8 weeks in best supportive care), while in KRAS mutant patients panitumumab showed no efficacy, however adverse events were more frequent and severe. According to SmPC, panitumumab is indicated as monotherapy for the treatment of patients with EGFR expressing metastatic colorectal carcinoma with non-mutated (wild-type) KRAS after failure of fluoropyrimidine-, oxaliplatin- , and irinotecan-containing chemotherapy regimens. Adverse events are similar as with other EGFR inhibitors: skin symptoms (rash), lung infiltrates, diarrhoea, ion abnormalities of renal origin. The drug was formerly available via named patient reimbursement, and now is financed by diagnosis-related group (DRG) system.