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.

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.

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.

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.

Comet assay is not useful to predict normal tissue response after radiochemotherapy in cervical and larynx cancer patients.

Normal tissues reactions after radiotherapy vary considerably even between patients receiving the same treatment. The ability to predict the differences in radiosensitivity before radiotherapy would have important implication. Patients with squamous cell carcinoma of the: (i) cervix (38 patients) and (ii) larynx (19 patients) were studied. Control group consisted of 9 healthy women. To assess individual radiosensitivity/chemoradiosensitivity alkaline version of comet assay was performed using isolated peripheral blood lymphocytes from cancer patients and healthy donors. The level of endogenous (0Gy), initial (immediately after 6Gy irradiation) and residual (after irradiation and 1h of repair) DNA damage was investigated. The mean value of endogenous damage was similar in control and cervical cancer (CCU) groups and significantly lower than in larynx cancer patients. Cancer patients showed slower DNA repair. For CCU and larynx patients, comet assay parameters were not helpful for unequivocal prediction of appearance of acute and late radiation reaction effects. Comet assay seems to be unable to predict normal tissue reaction after radiochemotherapy. Therefore, there is still need for developing predictive assays, however, due to complicated mechanism of chemoradiosensitivity, only assays assessing not one but many molecular pathways might gives us reliable score.

Methods and results of locoregional treatment of brain metastases in patients with non-small cell lung cancer.

This article presents methods and results of surgery and radiotherapy of brain metastases from non-small cell lung cancer (BMF-NSCLC). Patients with single BMF-NSCLC, with Karnofsky score ≥ 70 and controlled extracranial disease are the best candidates for surgery. Stereotactic radiosurgery (SRS) is recommended in patients with 1-3 BMF-NSCLC below 3-3.5 cm, with minor neurological symptoms, located in parts of the brain not accessible to surgery, with controlled extracranial disease. Whole brain radiotherapy (WBRT) following SRS reduces the risk of local relapse; in selected patients median survival reaches more than 10 months. Whole brain radiotherapy alone is a treatment in patients with multiple metastases, poor performance status, uncontrolled extracranial disease, disqualified from surgery or SRS with median survival 3 to 6 months. There is no doubt that there are patients with BMF-NSCLC who should receive only the best supportive care. There is a debate in the literature on how to select these patients.

Postoperative irradiation in patients with pT3-4N0 laryngeal cancer: results and prognostic factors.

Approximately 60 % of patients with locally advanced laryngeal cancer (LALC) treated primarily with surgery require adjuvant radiotherapy. In the available literature predominate series of patients were with pathologically confirmed node-positive status. Subgroups of pN0 patients with LALC are scarce. The aim of the study is to evaluate the efficacy of postoperative radiotherapy in patients with pathological stage T3-4N0M0 and identification of prognostic factors in this group. Between 1975 and 2005, 138 patients with squamous pT3-4N0 laryngeal cancer were irradiated postoperatively. Primary surgical treatment consisted of total laryngectomy and cervical lymphadenectomy. The median time between surgery and the implementation of radiotherapy was 56 days. The median total dose was 60 Gy (range 40-70 Gy). Five-year disease-free survival (DFS5) was achieved in 76 % of patients. Cancer recurrence was observed in 34 patients. In 28 (82 %) cases it was locoregional failure. DFS5 rates for pT3 and pT4 were 92 and 69 %, for margin status R0, R1 and R2 were 82, 72 and 67 %, respectively. The pharyngeal invasion was related to a decrease in DFS5 from 80 to 59 %. Postoperative irradiation in patients with pT3-4N0 LALC is an effective treatment method. The main reason of the failure is local recurrence. The following independent prognostic factors were identified in this group of patients: pT stage, surgical margin status and pharyngeal invasion.

Histopathological factors influencing results of combined treatment in patients with laryngeal cancer.

The aim of the study was to assess the prognostic value of postoperative histopathological factors as well as the clinical usefulness of the modified risk score for recurrence. In a group of 197 patients with laryngeal cancer who underwent surgery followed by radiation therapy, partial resection was performed in 21.5% of patients and total resection in 78.5%. The majority of patients had T3 or T4 (74%) and N0 (63%) cancer. Macroscopically positive margins were reported in 10% of patients after partial resection and in 7% of patients after total resection, whereas microscopically positive margins were observed in 31% and 20% of cases, respectively. Extracapsular extension was observed in 22% of patients. In order to estimate local and nodal recurrence risk rates, criteria developed by Peters were used. Five-year local control (LC) was achieved in 88% of patients, disease-free survival (DFS) in 68% of patients and overall survival (OS) in 73% of patients. In the case of macroscopically positive margins, the 5-year DFS was 33% lower compared to radical surgery and 25% lower in the case of microscopically positive margins. The 5-year DFS was reduced by 29% due to extracapsular extension. Cox model analysis indicated that the degree of recurrence risk was the most potent independent prognostic factor for postoperative radiation therapy in laryngeal cancer. Negative histopathological factors influencing results of combined treatment of laryngeal cancer include macro- and microscopically positive margins, neck lymph node involvement and extracapsular extension.

Distribution of podoplanin-positive tumor vessels predicts disease-specific survival of node-positive breast cancer patients treated with anthracyclines and/or taxanes.

We analyzed survival of 102 invasive ductal, node positive breast cancer patients, treated with surgery and adjuvant chemotherapy (anthracyclines and/or taxanes) with relation to: (a) well-known clinicopathological parameters, (b) MIB-1 labeling index (LI), (c) the distribution of podoplanin-positive vessels (DPV), expression of: (d) basal markers, and (e) fascin. Lower progression risk was found for patients with tumors characterized by (i) pN1 + pN2, (ii) MIB-1LI ≤ 28%, (iii) lack of lymphatic vessels or high tumor DPV than for patients with pN3, MIB-1LI > 28%, low DPV, respectively. Cox multivariate analysis revealed that both pN3 and low DPV were negative prognostic indicators.

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.

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.

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.

Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker.

Lymphangiogenesis is a potential indicator of cancer patients' survival. However, there is no standardisation of methodologies applied to the assessment of lymphatic vessel density. In 156 invasive ductal breast cancers (T  1/N+/M0), lymphatic and blood vessels were visualised using podoplanin and CD34, respectively. Based on these markers expression, four parameters were assessed: (i) distribution of podoplanin-stained vessels (DPV) - the percentage of fields with at least one lymphatic vessel (a simple method proposed by us), (ii) lymphatic vessel density (LVD), (iii) LVD to microvessel density ratio (LVD/MVD) and (iv) the expression of podoplanin in cancer-associated fibroblasts. Next, we estimated relations between the above-mentioned parameters and: (i) breast cancer subtype, (ii) tumour grade, and (iii) basal markers expression. We found that intensive lymphangiogenesis, assessed using all studied methods, is positively related to high tumour grade, triple negative or HER2 subtype and expression of basal markers. Whereas, the absence of podoplanin expression in fibroblasts of cancer stroma is related to luminal A subtype, low tumour grade or lack of basal markers expression. Distribution of podoplanin-stained vessels, assessed by a simple method proposed by us (indicating the percentage of fields with at least one lymphatic vessel), might be used instead of the "hot-spot" method.

[Predictive and prognostic value of p53, Ki-67 and EGFR in patients with advanced oral cavity and oropharyngeal cancer treated with induction chemotherapy]. / Ocena wartosci predykcyjnej i prognostycznej p53, Ki-67 i EGFR u chorych na zaawansowanego raka jamy ustnej i ustnej czesci gardla leczonych z zastosowaniem indukcyjnej chemioterapii.

BACKGROUND: To determine predictive and prognostic value of p53, Ki-67 and EGFR in patients with advanced oral cavity and oropharyngeal cancer treated with induction chemotherapy. MATERIALS AND METHODS: The data form 40 patients with advanced oral cavity and oropharyngeal cancer treated between January 1988 and December 1997 were analyzed retrospectively. All patients received 1 to 3 cycles of induction chemotherapy (ICHT) consisting of cisplatin and fluoruracil. Twenty two patiemts (68%) underwent subsequent radical radiotherapy. Histologic and immunohistochemical analyzes of p53, Ki-67 and EGFR were performed in all patients. RESULTS: Response to induction chemotherapy was obtained in 18 patients (45%). None of the analyzed factors significantly influenced the chance to obtain the response to chemotherapy. The 3-year loco-regional control and overall survival rates in the group of 22 patients treated radically were 20% and 23%, respectively. CONCLUSIONS: Lack of EGFR expression is favorable prognostic factor for overall survival in patients with advanced oral cavity and oropharyngeal cancer treated with induction chemotherapy.

Prognostic value of the interval from surgery to initiation of radiation therapy in correlation with some histo-clinical parameters in patients with malignant supratentorial gliomas.

AIM OF THE STUDY: To determine the relationship between the interval from surgery to initiation of radiation therapy (ISRT) and prognostic factors, such as age, performance status, tumour location, extent of surgical resection and tumour histology in patients with malignant gliomas. MATERIALS AND METHODS: From 1995 to 2005, 308 adults patients with supratentorial malignant gliomas (198 glioblastomas, and 110 anaplastic astrocytomas) received postoperative radiotherapy with radical intent. A total tumour dose of 60 Gy in 30 fractions in 6 weeks was delivered. ISRT varied from 15 to 124 days, with median time of 37 days, and it was a cut-off value to assess the results. The end point in our study was two-year overall survival. RESULTS: The two-year overall survival rate in the whole group was 17%, with 24% for patients with ISRT value ≤ 37 days, and 14% for patients with an interval longer than 37 days (p = 0.042). Univariate analysis showed that delayed initiation of radiotherapy influenced the outcome of patients with glioblastoma older than 40 years, and with other than frontal location of tumour. Two-year overall survival rates for ISRT ≤ 37 days were 15%, 18% and 22% respectively, compared to 8%, 4% and 11% for ISRT > 37 days. In a multivariate analysis (Cox's model) the only variables that were significantly associated with worse survival were older age and ISRT prolonged for more than 37 days. CONCLUSION: The study showed longer than 37 days waiting time from surgery to initiation of radiotherapy to be a significant predictor of overall survival for adult patients with malignant supratentorial gliomas.

Long-term follow-up in adult patients with low-grade glioma (WHO II) postoperatively irradiated. Analysis of prognostic factors.

AIM: To report the long-term follow-up of a cohort of adult patients with LGG post-operatively irradiated in one institution, and to identify prognostic factors for progression free survival. BACKGROUND: There is little consensus about the optimal treatment for low-grade glioma (LGG), and the clinical management of LGG is one of the most controversial areas in neurooncology. Radiation therapy is one option for treatment of patients with LGG, whereas other options include postoperative observation. MATERIALS AND METHODS: Between 1975 and 2005, 180 patients with LGG (WHO II) received postoperative irradiation after non radical (subtotal or partial) excision. Patients had to be 18 years of age or older, and have histologic proof of supratentorial fibrillary (FA), protoplasmic (PA) or gemistocytic astrocytoma (GA). Radiotherapy was given within 3-10 weeks after surgery. Treatment fields were localized and included the preoperative tumor volume, with a 1-2 cm margin, treated to a total dose of 50-60 Gy in 25-30 fractions over 5-6 weeks. RESULTS: Actuarial ten-year progression free survival (APFS) in the whole group was 19%. The worse prognosis was observed in patients with GA. Ten-year APFS rates for GA, PA and FA were 10%, 18% and 22%, respectively. CONCLUSION: The findings from our long-term cohort of 180 patients with LGG confirmed by uni- and multivariate analysis demonstrated that only astrocytoma histology significantly determined the prognosis. The best survival was observed in patients with the fibrillary variant, and the worst for the gemistocytic one.

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.