Outcome of COVID-19 infection in cancer patients during active systemic anticancer treatment. Single-institution experience. A retrospective analysis.

INTRODUCTION: Patients with cancer undergoing active systemic anticancer treatment (chemotherapy, immunotherapy, targeted, or combination therapy) are at greater risk of COVID-19 infection than persons without cancer. In this paper, the authors analyse the spread of the coronavirus among cancer patients undergoing systemic therapy, and the impact of COVID-19 infection on the continuation of cancer treatment and its outcome at one community hospital in a mid-sized city in the south of Poland. MATERIAL AND METHODS: Nasopharyngeal swab was the only collection method used to obtain specimens for testing via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Only those with positive RT-PCR results were considered as confirmed SARS-CoV-2 cases. We analysed the medical records of patients quarantined in a hospital clinical oncology ward due to confirmed COVID-19 infection in one member of the group. Qualitative measures are presented as the percentage of their occurrence, and these were evaluated with Fisher's test. Differences were considered significant at p < 0.05. RESULTS: Cancer patients had more frequent confirmed COVID-19 infection than other patients (3.7% vs. 1.2%). Among cancer patients COVID-19 infection was significantly more frequent in women than in men, p = 0.005. The fatality rate was 27.3% in cancer patients undergoing active anticancer therapy, compared to 3% in the general Polish population. Neither heparin nor G-CSF use had any influence on COVID-19 infection. CONCLUSIONS: In this analysis, the only significant negative factor for COVID-19 infection was female sex, RR (95% CI) = 4.5 (1.3-15.8), (p = 0.005), and this was attributable to individual behaviour.

Feelings Related to the COVID-19 Pandemic Among Patients Treated in the Oncology Clinics (Poland).

Background: The number of cancer patients is constantly growing. Both WHO and IARC report that this number may reach up to 24 million new diagnosed cases in the next two decades. The proposed treatment and especially the diagnosis can have a significant impact on an individual's approach to the disease, as well as on the patient's quality of life. Objectives: The study aimed to assess the quality of life, feelings, and fear of cancer-treating oncological patients, before and during the COVID-19 pandemic. Material and Methods: The study used the standardized WHOQOL quality of life questionnaire in a shortened version, the COVID-19 fear scale (FCV-19S), and the AIS disease acceptance scale (in terms of cancer-related sensations). The questionnaire survey was conducted among patients of cancer clinics (Poland). The study was conducted in two stages-before the COVID-19 pandemic (May 2019) and during the COVID-19 pandemic (May 2020). Data from 450 correctly completed questionnaires were analyzed statistically. The obtained data were statistically processed using the Kruskal-Wallis and Mann-Whitney U test (p = 0.05). Results: Among the surveyed patients of the cancer clinic, the quality of life during the COVID-19 pandemic decreased by 2%, compared to the period before the pandemic. The frequency of negative feelings associated with cancer increased during the COVID-19 pandemic-by 11% more men, and 4.4% of women determined the frequency of negative feelings to be 2-3 times a week. The level of fear associated with COVID-19 was moderate (57.1%), with women having a higher level of fear (12.5% higher than men). Conclusion: The development of the epidemic is very important in terms of public health. COVID-19 should be considered as one of the factors that bring about sudden changes in the mental health of the population, which may result from the dynamic development of this disease, dramatic media coverage, and own experiences. It has been shown that the sudden appearance of such a large stressor causes a decrease in patients' quality of life and an increase in negative feelings associated with chronic disease.

Hodgkin lymphoma of the elderly patients: a retrospective multicenter analysis from the Polish Lymphoma Research Group.

We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1-190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63-0.85) and 0.90 (95%CI: 0.82-0.98) for ES; 0.51 (95%CI: 0.44-0.57), and 0.81 (95%CI: 0.75-0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG <2 and age >70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG< 2, age >70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.

Dermoscopic assessment of skin toxicities in patients with melanoma during treatment with vemurafenib.

INTRODUCTION: The use of vemurafenib in melanoma has improved the survival of patients; however, it is associated with skin toxicities. AIM: To assess skin toxicities by dermoscopy in patients treated with vemurafenib. MATERIAL AND METHODS: Eight patients with BRAF V600 mutation positive metastatic melanoma were examined dermoscopically during vemurafenib treatment. All skin lesions occurring during therapy were assessed clinically and dermoscopically using a hand-held dermoscope with polarised and non-polarised light. Skin lesions suspected for malignancy appearing during therapy were totally surgically excised with consecutive histopathological examination. RESULTS: All 8 examined patients developed skin toxicity. The majority of patients (7/8) presented G1 skin toxicity according to CTCAE version 4.3. Only 1 of them had G2 skin toxicity. The most common dermoscopy findings in our study were hyperkeratotic verrucas in 5 patients (5/8) with structureless pattern. In some of them we also observed central dots, exophytic proliferation, hairpin vessels and homogeneous haemorrhage. Other findings were hyperkeratosis of the nipples (5/8) with brownish to yellowish, angular clods with a tendency to be more confluent in dermoscopy. Palmar plantar erythrodysaesthesia (3/8) showed dermoscopically a yellowish, homogeneous pattern. Four melanocytic skin lesions in 2 patients were surgically excised due to suspected malignant transformation. In most of them we observed an atypical pigmented network (abrupt cut-off, big holes), atypical globules and a homogeneous blue pattern; however, histopathological diagnosis excluded any malignancy. CONCLUSIONS: Dermoscopy seems to be an easily performed and valuable method for assessment of skin toxicities during oncological therapy, at any time of the treatment.

The association of tumor lymphocyte infiltration with clinicopathological factors and survival in breast cancer.

Recent studies have confirmed the role of tumor-infiltrating lymphocytes (TILs) in carcinogenesis and cancer progression. The aim of this study was to evaluate the correlation between the level of tumor lymphocyte infiltration and well-known clinicopathological factors in breast cancer patients. We also evaluated the influence of TILs on overall survival. Paraffin sections were retrospectively evaluated in 76 cases in early stage breast cancer patients who underwent surgery followed by systemic treatment. Tumor-infiltrating lymphocytes were classified as absent (grade 0), mild (grade 1), moderate (grade 2), or severe (grade 3). Tumor-infiltrating lymphocytes were found in 87% of patients (severe grade in 8% of them). Higher grade (grades 2-3) TILs were present more frequently in younger patients (under 65 years) than older women (47% vs. 24%; p = 0.099). Higher grades of tumor-infiltrating lymphocytes (grades 2-3) appear to be associated with clinicopathological factors such as negative steroid receptor status (p = 0.001), HER2 overexpression (p = 0.016) and higher histological grade (G3) (p = 0.095). Tumor-infiltrating lymphocytes were not a significant prognostic factor for overall survival in our group. Only HER2 overexpression significantly increases the risk of death (HR = 4.3, p = 0.020). In the subgroup of patients who had tumors with HER2 overexpression there was non-significantly worse OS independently of TIL grade (p = 0.086).

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio before chemotherapy as potential prognostic factors in patients with newly diagnosed epithelial ovarian cancer.

INTRODUCTION: Recent studies have shown that the presence of systemic inflammation correlates with worse outcomes in many types of cancers. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed as indicators of systemic inflammatory response. The aim of the study was to assess the prognostic value of NLR and PLR before starting chemotherapy among patients with newly diagnosed ovarian cancer. METHODS: We conducted a retrospective analysis of medical documentation of 315 patients with newly diagnosed epithelial ovarian cancer, treated in Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, between 2007 and 2013. 31 (12.1%) patients had metastatic disease at the time of diagnosis. Receiver-operating characteristic (ROC) curves for progression free survival (PFS) and overall survival (OS) prediction were plotted to verify cut-off points for NLR and PLR. PFS and OS were analysed for correlation with NLR and PLR, using the Cox regression model. Other potential prognostic variables included in multivariate analysis were: patient's age at diagnosis (<65 vs ≥65 years), Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2, FIGO stage of the disease and baseline Ca-125 level. RESULTS: In multivariate analysis, higher pretreatment NLR (p=0.002), poor ECOG-PS (p=0.0002), higher disease stage (p<0.0001) and baseline Ca-125 (p=0.03) level were independent negative prognostic factors for PFS. However, only ECOG-PS ≥2 (p<0.0001), high stage of the disease (p<0.0001) and high baseline Ca-125 level (p=0.0003) were independent negative prognostic factors for OS. CONCLUSIONS: Advanced stage of the disease with high Ca-125 level and poor patient performance status are the most important prognostic factors in ovarian cancer. Higher pretreatment value of NLR was an independent negative prognostic factor for PFS, with no significant impact on OS.

Efficacy and safety of vitamin D supplementation in patients with chronic lymphocytic leukemia.

BACKGROUND: Vitamin D (VD) deficiency in chronic lymphocytic leukemia (CLL) is associated with inferior prognosis, shorter time to treatment and worse overall survival. VD deficiency is the first potentially modifiable prognostic factor in CLL. Currently, however, there is a lack of studies concerning VD supplementation in CLL patients. AIM: To evaluate the efficacy and safety of VD supplementation in patients with CLL. METHODS: A 6-month interventional study was conducted in CLL patients with lower serum 25-OH-D3 concentrations (< 30 ng/ml) than currently recommended. Patients with VD insufficiency (20-30 ng/ml) received 2000 IU of cholecalciferol/day, patients with moderate deficiency (10-19.9 ng/ml) received 4000 IU/day, and patients with severe VD deficiency (<10 ng/ml) received 6000 IU/day. RESULTS: In the analyzed group of 13 CLL subjects, only 1 patient had a VD level within the optimal range (30-80 ng/ml), 7 had an insufficient concentration, 4 had moderate deficiency, and 1 had severe deficiency. Secondary hyperparathyroidism was diagnosed in 4 subjects. Cholecalciferol supplementation (mean dose of 3384 ± 1211 IU) was followed by a significant increase in 25-OH-D3 concentration (from 17.3 ± 5.8 to 41.4 ± 17.5 ng/ml; p<0.05) and decrease in PTH (p<0.05). Five patients did not achieve the recommended 25-OH-D3 concentration. Calcium level remained unchanged and no patients developed hypercalcemia. CONCLUSIONS: VD replenishment is safe and can be effectively achieved by means of the employed cholecalciferol dosage in the majority of patients. However, some subjects may require higher doses to obtain the optimal level and immune function.

Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients.

The HER2/neu (ERBB2) oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody - trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

Skin toxicity in BRAF(V600) mutated metastatic cutaneous melanoma patients treated with vemurafenib.

INTRODUCTION: The use of orally available BRAF kinase inhibitor - vemurafenib is associated with numerous adverse skin reactions. AIM: To assess the safety and early side effects of vemurafenib treatment in the unselected group of patients treated at the outpatient clinic, in particular the assessment of the incidence of skin cancer. MATERIAL AND METHODS: We carried out a systematic study of patients (pts) treated with vemurafenib. Skin toxicity during vemurafenib therapy was analyzed. Toxicity was determined on the basis of the toxicity scale CTCAE, version 4.0. RESULTS: The most common cutaneous side effects were hyperkeratotic perifollicular rash (69%) and photosensitivity (15%). Skin rash developed more frequently in the first month of treatment. Squamous cell carcinoma occurred in 38% of patients. Patients with skin cancer development during vemurafenib therapy had non-significantly longer overall survival (OS) than patients without skin cancer, p = 0.4. Skin cancer developed more often in women than in men (60% vs. 25%), p = 0.249. It was detected only in patients with normal weight compared to overweight patients (55% vs. 0), p = 0.09. The median OS was 26 months and median OS from the time of distant metastases diagnosis was 9.8 months. In patients with a low body mass index, shorter OS was observed, p = 0.09. CONCLUSIONS: The incidence of squamous cell carcinoma was high (38%). This study has many limitations mostly due to a small group of patients. That is why the results should be taken into consideration with caution. The proper symptomatic treatment in cooperation with dermatologists allows to continue the vemurafenib therapy.

A Comparison between CHEK2*1100delC/I157T Mutation Carrier and Noncarrier Breast Cancer Patients: A Clinicopathological Analysis.

OBJECTIVE: The suppressor gene CHEK2 encodes a cell cycle checkpoint kinase, involved in cell cycle regulation, apoptosis and response to DNA damage. The aim of this study was to analyze the differences between CHEK2 mutation carriers (CHEK2*1100delC/I157T) and noncarriers with respect to clinicopathological factors. METHODS: We reviewed the medical records of 100 early breast cancer patients (46 mutation carriers and 54 noncarriers) who were treated with chemotherapy, hormonotherapy or trastuzumab. RESULTS: CHEK2 mutation carriers were older (>65 years) than noncarriers (17 vs. 7%; p = 0.215). Twenty-five (54%) of them had a history of cancer in the family. Gastric cancer in the family history was detected in 11% of mutation carriers and in 2% of noncarriers (p = 0.092). There was a trend for more frequent lymph node metastases in patients without the mutation in comparison to mutation carriers (46 vs. 28%; p = 0.098). Luminal B type breast cancer was detected more often in carriers (39 vs. 20%; p = 0.048). Breast-conserving treatment was also conducted more often in mutation carriers (57 vs. 31%; p = 0.015). Histologic grades G1/G2 were detected more frequently in mutation carriers (82 vs. 70%; p = 0.212). CONCLUSION: Mutation carriers were characterized by older age, a history of gastric cancer in the family, locally advanced disease, lower histologic grade and luminal B type breast cancer.

Randomized clinical trial on 7-days-a-week post-operative radiotherapy vs concurrent post-operative radiochemotherapy in locally advanced cancer of the oral cavity/oropharynx: a report on acute normal tissue reactions.

OBJECTIVE: The purpose of the study was to evaluate acute normal tissue reactions and treatment compliance in a randomized clinical trial on 7-days-a-week post-operative radiotherapy (p-CAIR) vs post-operative concurrent radiochemotherapy (p-RTCT) in locally advanced cancer of the oral cavity/oropharynx. The sample analyzed at present represents approximately 30% of the intended future trial size. METHODS: The patients were randomly assigned to receive 63 Gy in 1.8-Gy fractions 7 days a week (n = 44) or 63 Gy in 1.8-Gy fractions 5 days a week with concurrent cisplatin 80-100 mg per square metre of body surface area on Days 1, 22 and 43 of the course of radiotherapy (n = 40). Acute mucosal reactions were scored using the modified Dische system. RESULTS: 15 (17.9%) patients, including 5 patients in p-CAIR and 10 patients in p-RTCT, did not comply with the assigned radiation treatment, mostly because of rapid tumour progression or deteriorating general performance. In p-RTCT, 22 (55%) patients received less than the intended three courses of chemotherapy mostly owing to haematological toxicity. The average maximum mucosal severity score was 14.2 in p-CAIR compared with 13.4 in p-RTCT; the difference was not statistically significant (p = 0.31). CONCLUSION: The schedules compared (p-CAIR and p-RTCT) did not differ considerably with respect to acute mucosal reactions. Haematological toxicity in p-RTCT was elevated compared with p-CAIR. Both schedules were considered tolerable with respect to acute toxicity, which justifies further recruitment to the trial. ADVANCES IN KNOWLEDGE: The results show that early mucosal reactions are comparable in both trial arms but haematological toxicity is more pronounced during radiochemotherapy.

C-C motif ligand 11 reduction in CLL patients serum after vitamin D supplementation.

BACKGROUND: Vitamin D (VD) deficiency results in a worse prognosis in patients with chronic lymphocytic leukemia (CLL) and may affect the production of cytokines. Nonetheless, there is the lack of studies dealing with VD supplementation and its impact on chemokines in CLL patients. AIM: The primary endpoint of our interventional study was to evaluate the effect of cholecalciferol supplementation on serum chemokines levels in CLL patients. MATERIALS AND METHODS: Eighteen subjects with CLL were enrolled for the study. Six-month-long cholecalciferol supplementation was performed in CLL patients with serum 25-OH-D3 levels below 30 ng/ml. Cytokines levels were assessed at the beginning of the study and after 6 months. Baseline measurements of cytokines were compared to those in apparently healthy controls. RESULTS: Increased levels of CCL2, CCL3, CCL4, CXCL8, CXCL10, TNFα, bFGF, G-CSF, and VEGF were found in CLL patients in comparison with the healthy controls. In the course of the VD supplementation a decrease in serum levels of chemokines CCL11, CCL3, and cytokine PDGF-BB was observed. The decrease of CCL11 was found in CLL patients on VD supplementation solely, whereas the decrease of CCL3 and PDGF-BB was observed in CLL subjects on both chemotherapy and VD supplementation. CONCLUSION: The VD supplementation may exert beneficial effect on chemokines levels in CLL patients with VD deficiency.

Treatment related toxicity in BRCA1-associated epithelial ovarian cancer - is DNA repairing impairment associated with more adverse events?

AIM OF THE STUDY: The presence of BRCA germline mutations in patients with ovarian cancer has been shown to have predictive and prognostic significance, including increased platinum-sensitivity. The aim of the study was to evaluate if patients with BRCA1-associated ovarian cancer have more treatment related adverse events and, if so, does it have impact on chemotherapy outcomes. MATERIAL AND METHODS: We conducted a retrospective analysis of medical records of 172 patients with newly diagnosed epithelial ovarian cancer, treated in Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch between 2007 and 2013. Ninety-six of these patients have known BRCA mutation status - 21 patients were BRCA1(+) and 75 BRCA1(-). Analysed treatment related adverse events (AE's) were: haematological toxicity, nausea/vomiting, neuropathy and mucositis. RESULTS: Grade 3-4 haematological AE's were significantly more common among BRCA1(+) patients (OR = 3.86; 95% CI: 1.14-13.23; p = 0.02). There was no association between BRCA1 mutation status and neuropathy (p = 0.73) or nausea/vomiting (p = 0.91). Occurrence of above mentioned AE's has no significant association with PFS (p = 0.75, 0.64, 0.97 respectively) and OS (p = 0.64, 0.69, 0.73 respectively). CONCLUSIONS: Among patients with BRCA1-associated epithelial ovarian cancer we observed significantly more grade 3-4 haematological complications after chemotherapy. However, occurrence of AE's did not correlate with better outcomes in this subgroup.

Risk factors for disease progression in HER2-positive breast cancer patients based on the location of metastases.

INTRODUCTION: Trastuzumab therapy significantly improves progression-free and overall survival in HER2-positive [HER2(+)] breast cancer (BC) patients. However, in most patients with HER2(+) metastatic BC, the disease progress occurred. The aim of this study was to evaluate the clinicopathological risk factors for progression in HER2-positive breast cancer patients during trastuzumab therapy. MATERIAL AND METHODS: The analysis included medical records of HER2(+) metastatic BC patients treated with trastuzumab between 2006 and 2013. RESULTS: The most common site of progression during trastuzumab therapy were lungs 25 (39%), central nervous system (CNS) 8 (13%), skin 9 (14%), locoregional lymph nodes 19 (30%), liver 18 (28%) and bone 17 (27%). Patients with lung metastases significantly more often had a history of cancer in the family than women with other metastasis sites (24% vs. 2.6%), p = 0.048. Metastases to lungs occurred also more often during therapy containing trastuzumab with chemotherapy than trastuzumab alone 17/8 (58% vs. 41%), p = 0.043. Central nervous system metastases were observed insignificantly more frequently in postmenopausal women than premenopausal patients 8/0 (22% vs. 0%), p = 0.093. There was reported a tendency to liver metastases in ER-negative tumors 13/20 (72% vs. 44%, p = 0.053). Bone metastases were associated with the positive steroid receptor status (p = 0.019) and second neoplasm in history (p = 0.06). CONCLUSIONS: Risk factors for disease progression were the menopausal status (CNS metastases), steroid receptor status (liver, lymph nodes and bone metastases), history of cancer in the family (lung metastases) and history of cigarette smoking (liver metastases).

The risk factors of toxicity during chemotherapy and radiotherapy in breast cancer patients according to the presence of BRCA gene mutation.

AIM OF THE STUDY: Treatment toxicity may decrease the treatment effectiveness due to the need to reduce the dose or increase the interval between cycles. The aim of this study was to distinguish the risk factors for treatment side effects in breast cancer patients and to assess the impact of BRCA1/2 mutations on the treatment toxicity. MATERIAL AND METHODS: The analysis was conducted on the medical history of 370 patients who were treated with anthracycline-based chemotherapy between 2006 and 2012 in the Clinical Oncology Department, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Gliwice in Poland (COI). All patients were tested for the presence of BRCA1 and BRCA2 mutations. RESULTS: In the studied group 13% (48) of the patients were BRCA mutation carriers. Neutropaenia after the first cycle of chemotherapy occurred more commonly in mutation carriers compared to non-carriers (29% vs. 10%), p = 0.0002. Radiotherapy acute skin toxicity was present in 3% of patients with similar rates in both groups, p = 0.950. Toxicity grade 3-4 was present more frequently in patients younger than 70 years (p = 0.02) of age, patients with viral hepatitis (p = 0.045), hypertension (p = 0.039), and cardiovascular disease (p = 0.044). Lower WBC count before treatment was observed more frequently in patients with neutropaenia (p = 0.002), especially in mutation carriers, p = 0.0015. CONCLUSIONS: Risk factors for anthracycline-based chemotherapy side effects were: age below 70 years, lower WBC value at baseline, history of infectious diseases, hypertension, and cardiovascular comorbidity. The presence of BRCA mutations may be a risk factor for neutropaenia, but it did not affect radiotherapy toxicity.

The influence of steroid receptor status on the cardiotoxicity risk in HER2-positive breast cancer patients receiving trastuzumab.

INTRODUCTION: Expression of steroid receptors and HER2 overexpression in breast cancer cells are predictive and prognostic factors. Overexpression of HER2 allows the use of immunotherapy, in which the most serious side effect is cardiotoxicity. The aim of this study was to evaluate the influence of steroid receptor status on cardiotoxicity risk in HER2 breast cancer patients receiving trastuzumab both in adjuvant treatment and in the case of disease dissemination. This study also assessed well-known cardiac risk factors. MATERIAL AND METHODS: The study was conducted on 166 patients who received immunotherapy in the Clinical and Experimental Oncology Department, between the years 2006 and 2012. RESULTS: A predisposition to cardiac side effects (13% vs. 5%) in patients with negative steroid receptor status was observed (p = 0.08). The decrease of left ventricular ejection fraction (LVEF) (12% vs. 0) and cardiac adverse side effects (2% vs. 0) were detected only in ER-/PR- patients but without statistical significance. Discontinuation of therapy because of cardiotoxicity was associated with negative receptor status (33% vs. 7%) (p = 0.019). Irrespective of steroid receptor status, older age of patients (p = 0.009) and previous radiotherapy to the left side of the chest (p = 0.02) were associated with the occurrence of cardiotoxicity and decrease of LVEF. In patients who received previous anthracycline-based chemotherapy, acute cardiac side effects were observed significantly more often (p = 0.01). CONCLUSIONS: There was no influence of steroid receptor status on the cardiac side effects. Breast cancer type containing Erb-B2 overexpression was associated with predisposition to cardiotoxicity. The results require confirmation in a larger group of patients.

Metaplastic breast carcinomas - analysis of prognostic factors in a case series.

AIM OF THE STUDY: Metaplastic breast carcinomas (MBC) are a rare group of cancers, accounting for about 1% of all breast cancers. The study presents a case series of MBC patients diagnosed, treated and followed up in one healthcare center. MATERIAL AND METHODS: The study group comprised 18 women at the median age of 63 years. The most common carcinoma type in the study group was MBC with squamous epithelial differentiation (56%). Estrogen receptor expression was identified in one patient. No steroid or HER2 receptor expression was found in the remaining patients. We analyzed recurrence and survival rates in relation to clinical and therapeutic factors by using the Kaplan-Meier method. RESULTS: A significantly longer overall survival time was noted among patients treated with adjuvant radiation therapy, p = 0.018. No other factors had a significant influence on survival. Because of the small size of the study group, results obtained in the study should be treated with caution.

Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer.

PURPOSE: Panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody (mAb), has demonstrated efficacy in patients with wild-type KRAS metastatic colorectal cancer (mCRC). Rilotumumab and ganitumab are investigational, fully human mAbs against hepatocyte growth factor (HGF)/scatter factor and IGF1R, respectively. Here we evaluate combining rilotumumab or ganitumab with panitumumab in previously treated patients with wild-type KRAS mCRC. EXPERIMENTAL DESIGN: Part 1 was a phase Ib dose-finding study of panitumumab plus rilotumumab. The primary endpoint was the incidence of dose-limiting toxicities (DLT). Part 2 was a randomized phase II trial of panitumumab in combination with rilotumumab, ganitumab, or placebo. The primary endpoint was objective response rate (ORR); safety, progression-free survival (PFS), and overall survival (OS) were secondary endpoints. Archival tissue specimens were collected for exploratory correlative work. RESULTS: In part 1, no DLTs were reported. A recommended phase II dose of 10 mg/kg rilotumumab was selected. In part 2, for the panitumumab plus rilotumumab (n = 48), panitumumab plus ganitumab (n = 46), and panitumumab plus placebo arms (n = 48), the ORRs were 31%, 22%, and 21%, respectively. The median PFS was 5.2, 5.3, and 3.7 months and median OS 13.8, 10.6, and 11.6 months, respectively. Adverse events were tolerable. Exploratory biomarker analyses, including MET and IGF-related protein expression, failed to indicate conclusive predictive evidence on efficacy endpoints. CONCLUSIONS: Panitumumab plus rilotumumab met the prespecified criterion for improvement in ORR whereas ganitumab did not. This is the first study to suggest a benefit for combining an HGF inhibitor (rilotumumab) with panitumumab in previously treated patients with wild-type KRAS mCRC.

Does routine clinical practice reproduce the outcome of large prospective trials? The analysis of institutional database on patients with limited-disease small-cell lung cancer.

We performed the analysis of database on 409 patients with LD-SCLC to evaluate as to what extent the clinical outcome of large prospective trials was reproduced in routine practice. The analysis has shown that the hazard rate of death in the absence of prophylactic cranial irradiation (PCI) adjusted for the effects of confounding factors, appeared larger than that reported in the trials on PCI in LD-SCLC, and was comparable to that estimated for extensive disease. Less intense routine staging procedures, compared to the trial settings, contributed for such outcome. Hyperfractionated thoracic radiotherapy provided survival advantage similar to that reported in the literature.