Non-metastatic primary neuroendocrine neoplasms of the breast: a reference cancer center's experience of a heterogenous entity.

Background: Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. Methods: The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. Results: We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Conclusion: Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi­centre experience.

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.

Differences between Squamous Cell Carcinomas of the Base of the Tongue and the Tonsils in Prevalence of HPV16 Infection, Its Type, and Clinical Features.

Regarding attempts to find de-escalation methods of treatment for patients with HPV16-positive squamous cell carcinoma of the oropharynx (OPSCC), there is an urgent need to identify new prognostic factors which allow physicians to differentiate the prognosis of these patients. The aim of the study is to compare the incidence of transcriptionally active HPV16 infection and its type as well as other epidemiological, clinical, and histopathological features between SCC of the base of the tongue (BOTSCC) and tonsils (TSSCC). The analysis was performed in a group of 63 patients with OPSCC, for which, in our earlier studies, we assessed transcriptionally active HPV16 infection and its type (viral load and viral genome status). Transcriptionally active HPV16 infection was significantly more common in TSSCC (96.3%) than in BOTSCC (3.7%). Patients with TSSCC had significantly higher disease-free survival rates (84.1%) than those with BTSCC (47.4%); the same was true in the subgroup with HPV16 positivity. The obtained results are an important indication for further research on the development of new prognostic and/or predictive factors for patients with HPV16-positive squamous cell carcinomas of the oropharynx.

The Vitamin D Status in Children With Newly Diagnosed Acute Lymphoblastic Leukemia and Its Potential Impact on the Primary Symptoms of Leukemia and Course of Induction Treatment.

BACKGROUND: Vitamin D deficiency is ubiquitous within the population of children. A similar problem is recognized among pediatric patients with acute lymphoblastic leukemia. The purpose of this study was to analyze the prevalence of vitamin D deficiency and to investigate the connection between vitamin D status and the course of induction treatment of ALL. MATERIALS AND METHODS: A cross-sectional study including 59 patients with newly diagnosed ALL from May 2017 until November 2020. RESULTS: Vitamin D deficiency was found in 39% of the patients. There were no seasonal differences in vitamin D status. Patients with optimal 25(OH)D concentration presented more profound thrombocytopenia ( P =0.015) and required more frequent platelet transfusions ( P =0.018). Good prognosis factors such as B phenotype and hyperdiploidy were also more frequent among children with higher 25(OH)D concentration ( P =0.01 and 0.014, respectively). CONCLUSIONS: The study showed that patients with a higher serum concentration of 25(OH)D presented deeper thrombocytopenia and needed more frequent transfusions. Moreover, those patients showed higher rates of B-cell leukemia and hyperdiploid karyotype. We did not find any influence of the possible exposure to sunlight (defined as the season of the year on admission) on serum 25(OH)D concentration, which supports the argument for supplementing vitamin D all year round. Moreover, the supplementing of vitamin D seems to be safe and does not cause any renal complications connected to calcium and phosphorus imbalance as no correlation between their levels and 25(OH)D concentration was found.

Cancer care for Ukrainian refugees during the first 6 weeks of 2022 Russian invasion - An experience of a cancer reference centre in Poland.

BACKGROUND: On 24th of February 2022, Ukrainian cancer patients had to face a new war. Here we describe an experience of the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow in providing cancer care for Ukrainian refugees during the initial 6 weeks of war. We present patients' characteristic, point out the main challenges and share initiatives undertaken. MATERIALS AND METHODS: For this cross-sectional analysis, we have gathered demographic and clinical data together with date of crossing the Polish-Ukrainian border for 112 Ukrainian refugees with cancer who had their first-time oncology consultation between 24th February and 8th April 2022. We have also implemented national guidelines and created local procedures, interventions and policies to manage this situation. RESULTS: The peak of patient inflow was the third week of War and refugees accounted for 13% of all first-time patients within that period of time. The majority of refugees were women (86%), treated radically (57%) with breast cancer (43%). Most of the patients required systemic treatment (67%). Amongst the main challenges at the time were differences in the reimbursement system, communication issues, lack of patients' documentation or tissue samples, prolonged diagnostic or treatment interruptions, increased risk of COVID-19 infections, chemotherapy side effects, and lack of procedures. Legal, procedural and organizational steps implemented at the local and national level were described. CONCLUSIONS: The Russian invasion on Ukraine forced an unexpectedly high number of Ukrainian cancer patients to seek help abroad, leading to the straining of the health care system in Poland.

Discrepancy between Tumor Size Assessed by Full-Field Digital Mammography or Ultrasonography (cT) and Pathology (pT) in a Multicenter Series of Breast Metaplastic Carcinoma Patients.

Metaplastic breast cancer (BC-Mp) presents diagnostic and therapeutic complexities, with scant literature available. Correct assessment of tumor size by ultrasound (US) and full-field digital mammography (FFDM) is crucial for treatment planning. METHODS: A retrospective cohort study was conducted on databases encompassing records of BC patients (2012-2022) at the National Research Institutes of Oncology (Warsaw, Gliwice and Krakow Branches). Inclusion criteria comprised confirmed diagnosis in postsurgical pathology reports with tumor size details (pT) and availability of tumor size from preoperative US and/or FFDM. Patients subjected to neoadjuvant systemic treatment were excluded. Demographics and clinicopathological data were gathered. RESULTS: Forty-five females were included. A total of 86.7% were triple-negative. The median age was 66 years (range: 33-89). The median pT was 41.63 mm (6-130), and eight patients were N-positive. Median tumor size assessed by US and FFDM was 31.81 mm (9-100) and 34.14 mm (0-120), respectively. Neither technique demonstrated superiority (p > 0.05), but they both underestimated the tumor size (p = 0.002 for US and p = 0.018 for FFDM). Smaller tumors (pT1-2) were statistically more accurately assessed by any technique (p < 0.001). Only pT correlated with overall survival. CONCLUSION: The risk of underestimation in tumor size assessment with US and FFDM has to be taken into consideration while planning surgical procedures for BC-Mp.

Prognostic Significance of STING Immunoexpression in Relation to HPV16 Infection in Patients with Squamous Cell Carcinomas of Oral Cavity and Oropharynx.

Infection with HPV16 in cancers of the oral cavity (OCSCC) and oropharynx (OPSCC) is, today, an important etiological and prognostic factor. Patients with HPV-positive OPSCC have a better prognosis than uninfected patients. However, in over 40% of these patients, cancer progression is noticed. Their identification is particularly important due to the ongoing clinical trials regarding the possibility of de-escalation of anticancer treatment in patients with HPV-positive OPSCC. Some studies suggest that there is possibility to differentiate prognosis of HPV16-positive patients by STING (Stimulator of Interferon Genes) immunoexpression. The aim of the present study was to analyze the influence of STING immunoexpression on overall (OS) and disease-free survival (DFS) of patients with HPV16-positive and -negative OCSCC and OPSCC. The study was performed in a group of 87 patients with OCSCC and OPSCC for which in our earlier study active HPV16 infection was assessed by P16 expression followed by HPV DNA detection. To analyze STING immunoexpression in tumor area (THS) and in adjacent stromal tissues (SHS) H score (HS) was applied. In the subgroup with HPV16, active infection patients with tumors with THS had significantly better DFS (p = 0.047) than those without THS. In this subgroup, TSH did not significantly influence OS, and SHS did not significantly correlate with OS and DFS. In the subgroup of patients without active HPV16 infection, THS and SHS also did not significantly influence patients' survival. Presented results indicated prognostic potential of tumor STING immunoexpression in patients with active HPV16 infection in cancers of oral cavity and oropharynx.

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.

Nanog expression in patients with squamous cell carcinoma of oropharynx in relation to immunohistochemical score.

This study aimed to compare prognostic potential of Nanog expression analysed by three immunohistochemical scores in the group of 63 squamous cell carcinomas of oropharynx. Immunoreactivity of Nanog expression was analyzed by semiquantitative score, immunoreactive score and H-score. For all three scores, the cut-off points for Nanog overexpression and its lack, allowing for optimal separation of overall and disease free survival curves, were search by minimal p-value method. In semiquantitative score, the best separation of overall and disease free survival curves was obtain by cut-off point lack of staining vs. week/moderate/strong staining, although statistical significance was not reach (OS: HR = 1.016, p = 0.081, DFS: HR = 6.876, p = 0.061). The cut-off points for immunoreactive score and H-score were, respectively: 1 (OS: HR = 6.977, p = 0.014, DFS: HR = 6.002, p = 0.019) and 50 (OS: HR = 6.977, p = 0.014, DFS: HR = 6.002, p = 0.019). The cut-off points found for these two scores allow to identify the same subgroups of patients with lack of Nanog expression (11.1%) and its overexpression (88.9%). All patients with tumors characterized by lack of Nanog overexpression identifying by immunoreactive score and H-score survived 5 years without evidence of cancer progression. In multivariate analysis Nanog immunoreactivity analysed by QRS and IRS was independent prognostic factor for OS (HR = 10.195, p = 0.024). Immunohistochemical score using to distinguish Nanog overexpression or its lack has influence on prognostic potential of this biomarker.

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.

Lack of CD44 and Sox-2 Overexpression as Two Independent Favourable Prognostic Factors in HPV Positive Patients with Oropharyngeal Cancers.

INTRODUCTION: In our earlier publications, in the group of 63 patients with oropharyngeal cancer, we have found HPV16 infection (assessed by qPCR) in 25 tumours (39.7%), immunohistochemical overexpression of CD44, CD98, ALDH1/2 and Nanog in, respectively: 43 (68.2%), 30 (47.6%), 33 (52.4%), and 53 (84.1%) cancers. Analysing CD44, CD98, ALDH1/2, we have also shown that lack of CD44 overexpression indicates excellent prognosis in patients with HPV16 positivity. The aim of the present study was to compare prognostic potential of Nanog, Oct3/4, Sox-2 expression in relation to CD44, CD98, ALDH1/2 immunoreactivity (assessed by us earlier) and clinicopathological features in the subgroups of patients: with HPV16 positivity and HPV16 negativity. METHODS: Status of Oct3/4 and Sox-2 expression was assessed for 63 patients with oropharyngeal cancers based on immunohistochemistry. In survival analysis, two endpoints were applied: overall survival (OS) and disease-free survival (DFS). RESULTS: Overexpression of Oct3/4 and Sox-2 was found in 0 (0.0%) and 27 (42.9%) of patients. In the subgroup with HPV16 positivity, the DFS for patients with lack of Sox-2 overexpression was significantly (p = 0.003) higher than for patients with Sox-2 overexpression. In the subgroup with HPV16 negativity, Nanog and Sox-2 immunoexpression did not significantly influence OS and DFS. In multivariate analysis performed for the subgroup with HPV16 positivity, lack of CD44 overexpression (p = 0.012) and lack of Sox-2 overexpression (p = 0.027) were positive independent prognostic factors. CONCLUSION: Based on CD44 and Sox-2 immunoreactivity, it is possible to differentiate the prognosis of HPV16-positive patients with oropharyngeal cancers.

Prognostic potential of Akt, pAkt(Ser473) and pAkt(Thr308) immunoreactivity in relation to HPV prevalence in head and neck squamous cell carcinoma patients.

BACKGROUND: The prognosis of squamous cell carcinoma of head and neck (HNSCC) patients remains relatively poor over the last years. Tobacco, alcohol and active human papillomavirus (HPV) infection are involved in HNSCC development. Akt is a serine-threonine protein kinase with main phosphorylation sites at Thr308 and Ser473, which are critical to generate a high level of Akt activity. MATERIALS AND METHODS: The aim of the study was to compare the expression and prognostic potential of total Akt and its 2 phosphorylated forms - pAkt(Ser473) and pAkt(Thr308) in relation to HPV status in HNSCC patients. The expression levels of proteins were assessed immunohistochemically. To select independent prognostic factors univariate and multivariate analyses with Cox proportional regression model were performed. RESULTS: Among HNSCC with active HPV16 infection significantly more tumors with high Akt (67.86%, p = 0.026) and low pAkt(Ser473) (64.29%, p = 0.000) expressions were found as compared to those with HPV negativity, while there was no significant difference in the pAkt(Thr308) expression level between HPV positive and negative tumors (p = 0.359). In the whole group of HNSCC patients independent favorable prognostic factors were low T stage, low pAkt(Thr308) expression, HPV16 active infection presence (for OS and DFS) and female gender (for OS only). CONCLUSIONS: Our results indicate an important role of pAkt(Thr308) as prognostic biomarker for HNSCC patients. There is a high probability that using Akt inhibitors would improve therapeutical benefits and treatment effectiveness, especially in HNSCC patients with high expression of pAkt.

Low frequency of HPV positivity in breast tumors among patients from south-central Poland.

BACKGROUND: Some studies suggest that Human Papilloma Virus (HPV) infection is important factor in carcinogenesis of breast tumors. This study' objective was to analyze HPV prevalence in breast cancers of patients from south-central Poland. MATERIALS AND METHODS: The study was performed based on archival paraffin embebbed and formalin fixed blocks in the group of 383 patients with breast cancer. HPV prevalence and its genotype were assessed, respectively by: nested PCR (with two groups of primers: PGMY09/PGMY11 and GP5+/GP6+), quantitative PCR (qPCR). Tumors were classified as HPV positive in case of at least one positive result in nested PCR and positive results in genotyping procedure. For all HPV positive tissues P16 immunostaining was applied in order to confirm active viral infection. RESULTS: In the group of 383 breast cancers, HPV positivity was found in 17 samples (4.4%) in nested PCR. All these samples were subjected to HPV genotyping. This analysis revealed presence of HPV type 16 into two tumors (0.5%). In these two cancers, P16 overexpression was reported. CONCLUSION: In breast tumors of patients from south-central Poland in Poland, HPV positivity is demonstrated in very low percentage of cases.

Complex grade III astrocytoma with granular cells and PXA features in a patient with tuberous sclerosis complex (Bourneville-Pringle syndrome) - case report and review of literature.

Tuberous sclerosis complex (Bourneville-Pringle syndrome) is a rare genetic condition included in the group of diseases called phakomatoses. Most of the patients are diagnosed with abnormalities within the central nervous system and tend to develop tumors more frequently, especially gliomas. We present a case of 50-year-old patient suffering from tuberous sclerosis complex, who had been diagnosed with pleomorphic xanthoastrocytoma (PXA). The patient underwent surgery and adjuvant radiotherapy and has remained free from local recurrence for 5 years.

Prognostic factors in elderly patients with T1 glottic cancer treated with radiotherapy.

The aim of the study was the evaluation of the effectiveness of radiotherapy in elderly T1 glottic cancer patients and prognostic factors with particular focus on comorbidities. Five-year overall survival, disease-specific survival, and local control rates were 63%, 92%, and 93%, respectively. Multivariate analysis showed that the following factors had statistically significant impact on local relapse risk and cancer death risk: diabetes, underweight, and fraction dose of 2 Gy. High number of comorbidities, high CCI, and underweight negatively influenced overall survival. A retrospective analysis was performed in a group of 131 T1N0M0 glottic cancer patients aged 70 and above treated with irradiation at the National Institute of Oncology in Cracow between 1977 and 2007. In the analyzed group men prevailed (92%) of mean age of 74 years. Each patient was diagnosed with at least one comorbidity with the following comorbid conditions being most frequent: hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. In the studied group, the effect of comorbidities on overall survival was evaluated using Charlson Comorbidity Index (CCI). Twenty five (19%) patients showed underweight. All patients were irradiated once daily, 5 days a week, to a total dose of 60-70 Gy with a fraction dose of 2 or 2.5 Gy. Radiotherapy is an effective treatment modality in elderly T1 glottic cancer patients. Diabetes as comorbidity, underweight, and conventional dose fractionation decrease the probability of curative effect of radiotherapy in this group of patients, while high number of comorbidities diminishes the probability of long-term survival.

Assessment of HPV16 infection in patients with laryngeal cancer.

The purpose of the study was to investigate HPV16 infection in laryngeal cancer patients treated with surgery and adjuvant radiotherapy as well as to analyze treatment results in relation to HPV16 infection and selected clinical, histopathological, and radiotherapy parameters. A retrospective analysis was performed in a group of 60 patients with squamous cell carcinoma of the larynx treated surgically and qualified for adjuvant radiotherapy at the Oncology Center in Cracow between 1995 and 2001. The studied group consisted of 57 men (95%) and 3 women (5%) of mean age of 56 years. In 13 patients (22%) underweight was noted. In the analyzed material, locally advanced laryngeal cancer prevailed (pT3-pT4) - 52 cases (87%), with the involvement of cervical lymph nodes (pN+) - 32 cases (53%). Histopathological examination revealed that microscopic radicality was not obtained in 18 patients (30%). Human papillomavirus 16 infection status as well as infection type (integrated, episomal, or mixed) were assessed in each patient by means of quantitative polymerase chain reaction (qPCR) using real-time detection. The 5-year OS, DFS, and LC rates were 45%, 61%, and 69%, respectively. Multivariate analysis revealed that local relapse risk and local failure risk were statistically significantly influenced by underweight and positive surgical margin. Underweight had also a statistically significant impact on death risk. The HPV16 infection was noticed in 4 cancers (6.8%). In all cases it was the same episomal type. On the basis of our observations it can be assumed that HPV infection does not play an important role in etiology of laryngeal cancer. Although, further study is needed in larger patient populations; optimal methodology for detecting HPV infection should also be determined. Positive surgical margin has a significant effect on worse treatment outcomes. Underweight before radiotherapy diminishes the probability of treatment success and survival of laryngeal cancer patients.

EGFR/PI3K/Akt/mTOR pathway in head and neck squamous cell carcinoma patients with different HPV status.

The aim of the study was to compare prognostic potential of PIK3CA mutations and expression of proteins involved in or regulate EGFR/PI3K/Akt/mTOR signaling in HPV16 positive and HPV negative head and neck squamous cell carcinoma (HNSCC) patients. The expression of proteins (EGFR, Akt, pAkt(Ser473), pAkt(Thr308), mTOR, PTEN, pPTEN, APOBEC3B) were assessed immunohistochemically and PIK3CA mutations (p.E542K, p.E545K, p.H1047R) by qPCR. Significantly more HPV16 positive tumors (89.29%) with low EGFR expression were found as compared to HPV negative ones (58.82%). PIK3CA mutations were detected in 7.14% of HPV16 positive and 2.5% of HPV negative cancers. In HPV16 positive patients survival analysis has shown that positive prognostic potential for disease free survival (DFS) had low expression of APOBEC3B. In HPV negative patients prognostic significance for DFS had APOBEC3B, Akt and pAkt(Thr308) levels, and for overall survival (OS) - pAkt(Thr308) only. Independent favorable prognostic factors in the whole group of patients were: low T stage, low pAkt(Thr308) expression, active HPV16 infection (for OS and DFS) and female gender (for OS). Obtained results suggest the existence of significant differences in expression and prognostic potential of proteins involved in EGFR/PI3K/Akt/mTOR signaling between HPV16 positive and HPV negative HNSCC patients.

Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group.

The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1-18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. Improvements in supportive care and emphasis placed on the determination of minimal residual disease at successive time points, which will impact decisions on therapy, may be required.

Active HPV infection and its influence on survival in head and neck squamous-cell cancer.

PURPOSE: HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients. METHODS: Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors. RESULTS: Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%, p = 0.000; DFS 93.0% vs. 53.35%, p = 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence. CONCLUSIONS: High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.