Role of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio and platelets in prognosis of patients with prostate cancer.

The aim of the present analysis was to evaluate the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelets (PLT) and neutrophil level for their prognostic values in patients with prostate cancer who had been treated with radiotherapy. A retrospective analysis of 152 patients who were treated in the Radiotherapy Department at Maria Sklodowska-Curie National Research Institute of Oncology (Gliwice, Poland) between January 2012 and December 2014 was performed. The prognostic value (overall survival; OS) of the pre-treatment PLR, NLR, LMR, PLT, neutrophil level and other laboratory factors such as: leukocyte, lymphocyte, monocyte, hemoglobin, RBC, prostate-specific antigen level (PSA), Gleason score, age, smoking and comorbid condition were assessed using univariate analysis. The cut-off point was determined for NLR as 'elevated' at >4.66, LMR >3.26 and the PLR was considered 'elevated' at >89.6. Median follow-up was 4.9 years. The 5 and 7-year OS rates were 81.5 and 72.2%, respectively. In univariate analysis higher NLR (P=0.007), higher level of PLT (P=0.004), higher level of neutrophils (P=0.013), elevated level of leukocyte (P=0.043) and lymphocyte (P=0.043) were factors significantly associated with decreased OS. No difference was found for PLR (P=0.308) and LMR (P=0.109). The other factor associated with decreased OS were: higher Gleason score (>7; P=0.005), higher PSA level (>20 ng/dl; P=0.0001), smoking (P=0.003) and older age (>70 years; P=0.018). In multivariate analysis, NLR, LMR, leukocyte and RBC were independently associated with prognosis in patients with prostate cancer. Elevated pre-treatment NLR [hazard ratio (HR)=10.83; P=0.001), LMR (HR=3.14; P=0.007) and higher leukocyte level (HR=3.14; P=0.007) were independently associated with increased mortality risk. Overall, pre-treatment NLR, PLR, leukocyte and RBC levels were revealed to be independent prognostic factors.

Analysis of Selected Nutritional Parameters in Patients with HPV-Related and Non-HPV-Related Oropharyngeal Cancer before and after Radiotherapy Alone or Combined with Chemotherapy.

Background: Radiotherapy plays an essential role in the treatment of oropharyngeal carcinoma (OPC). The aim of this study was to assess and compare the nutritional status (NS) of patients with HPV-related (HPV+) and non-HPV-related (HPV-) OPC before and after radiotherapy (RT) or chemoradiotherapy (CRT). Methods: The analysis included 127 patients with OPC who underwent radiotherapy (RT) alone, or in combination with chemotherapy (CRT), in the I Radiation and Clinical Oncology Department of Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (formalin-fixed, paraffin-embedded) tissue material and/or extracellular circulating HPV DNA. Basic anthropometric and biochemical parameters before and after RT/CRT were compared between the HPV- and HPV+ groups. The effect of NS on survival was also analyzed. Results: In both groups, a significant decrease in all analyzed nutritional parameters was noted after RT/CRT (p < 0.01). CRT caused significant weight loss and decreases in BMI, albumin, total lymphocyte count (TLC), and hemoglobin concentration, as well as an increase in the Nutritional Risk Score (NRS) 2002, in HPV- and HPV+ patients. A significant decrease in prealbumin levels after CRT was noted only in HPV+ patients. RT caused a significant decrease in hemoglobin concentration and TLC in HPV- patients. There were no significant differences regarding other nutritional parameters after RT in either group. RT did not have negative impact on body mass index (BMI), weight, NRS, CRP, Alb, Prealb, or PNI. Overall survival (OS) and disease-free survival (DFS) were significantly better in patients with a higher BMI in the HPV- group (OS, p = 0.011; DFS, p = 0.028); DFS was significantly better in patients with C-reactive protein (CRP) < 3.5 g/dL in the HPV- (p = 0.021) and HPV+ (p = 0.018) groups, and with total lymphocyte count (TLC) >1.28/mm3 in the HPV+ group (p = 0.014). Higher NRS 2002 was an independent adverse prognostic factor for OS and DFS in HPV-, but not in the HPV+ group. Kaplan−Meier analysis showed that both OS and DFS were significantly better in HPV- patients with lower NRS 2002 scores. However, this relationship was not observed in the HPV+ group. Conclusions: Regardless of HPV status, patients with OPC can develop malnutrition during RT/CRT. Therefore, nutritional support during RT/CRT is required in patients with HPV- and HPV+ OPC.

Overall survival analysis of > 65-year-old patients with breast cancer based on their molecular, clinicopathological and laboratory factors.

Introduction: The objective of the present study was to characterize > 65-year-old patients with breast cancer according to clinicopathological, molecular and laboratory factors. Methods: A total of 723 breast cancer patients, who had been diagnosed and treated during 2005-2019, were retrospectively reviewed. Patients > 65 years of age (92 patients) were compared with < 50-year-old women (306 patients). We analyzed 398 women from 723 patients. Results: Overall survival analysis was conducted for both groups, separately and combined. Patients with BC aged > 65 years were characterized by G1-2, higher lymphocyte values, lower platelet (PLT) counts and lower NLR or PLR values than patients < 50 years of age. Conclusions: Age > 65 years is a negative prognostic factor independent of other factors.

Pre-operative high-dose-rate brachytherapy in early-stage cervical cancer: long-term single-center results.

PURPOSE: The aim of the study was to report the outcomes of pre-operative high-dose-rate brachytherapy (pHDR-BT), followed by hysterectomy in patients with early cervical cancer. MATERIAL AND METHODS: From January, 1998 to December, 2003, 113 women with IB1, IB2, and IIA1 cervical cancer (according to International Federation of Gynecology and Obstetrics [FIGO] 2018) were treated with pHDR-BT, and 6 to 8 weeks later followed by radical hysterectomy. Patients found to have positive lymph nodes, residual cervical cancer, involved parametria, or lymphovascular space invasion (LVSI) received post-operative adjuvant therapy. RESULTS: Post-operatively, 81.4% of patients had a complete response to pHDR-BT in the cervix, and 18.6% had residual cervical cancer. Failures occurred in 11/113 (9.7%) patients (all were stage IIA1), with pelvic recurrences in 5/113 (4.4%) and distant metastasis (DM) in 6/113 (5.3%). The 5- and 10-year disease-free survival (DFS) rates were 100% for IB1 and IB2, and 86.4% and 81.3% for IIA1, respectively. Lymph node involvement and/or residual cervical cancer correlated with worse DFS. Two vesicovaginal fistulas were observed (one in a patient treated only with pHDR-BT and one in a woman, who underwent adjuvant external-beam radiotherapy [EBRT]). Two rectovaginal fistulas and one case of proctitis were observed in patients treated with adjuvant EBRT. CONCLUSIONS: pHDR-BT in early cervical cancer is well-tolerated and effective in sterilizing tumor cells in the cervix. The growing number of publications in this area may help define an optimal therapeutic scheme, but randomized trials are required to determine the best candidates for this treatment modality.In our opinion, cervical cancer patients with FIGO stage IIA1 are not good candidates for pHDR-BT, and could be given this treatment only after rigorous selection, including assessment with state-of-the-art imaging, due to higher probability of treatment failure.

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.

Stereotactic radiotherapy is a useful treatment option for patients with medullary thyroid cancer.

The role of radiotherapy in advanced medullary thyroid carcinoma (MTC) is confined to patients in whom surgical treatment or the administration of tyrosine kinase inhibitors are not possible or contraindicated. High fractionated radiation doses during radiosurgery or fractionated stereotactic radiotherapy are applied to reduce cancer-related symptoms and stabilize irradiated lesions. This study aimed to retrospectively evaluate the therapeutic effect of stereotactic radiotherapy in MTC patients. MATERIAL AND METHODS: The study group involved 11 MTC patients, treated due to 16 cancer lesions, mainly bone metastases (10 lesions), lymph node (2 lesions) metastases, or liver metastases (2 lesions), one primary thyroid tumor, and one MTC recurrence in the thyroid bed. The fractionated and total radiation doses ranged between 5 and 12 Gy and 8-44 Gy, respectively. Six lesions were treated with a single radiation fraction, three lesions with 2 fractions, another 6 lesions with 3 fractions, whereas the remaining one metastatic lesion with 9 fractions of stereotactic radiosurgery. RESULTS: The beneficial effect of stereotactic radiosurgery was obtained in all treated lesions. None of treated lesions progressed in the further disease course. Fourteen lesions were stable (87.5 %), including eight lesions showing progression before radiosurgery (good response). Disease control was obtained in all soft-tissue metastases. Regarding bone metastases, partial regression was achieved in 20 % lesions, whereas in 30 % lesions progressive before radiotherapy, the treatment led to disease stabilization. CONCLUSIONS: Our data pointed to the effectiveness of high-dose fractionated radiotherapy in MTC. However, an observation of a larger group of patients is required to confirm it.

Comparison of Selected Immune and Hematological Parameters and Their Impact on Survival in Patients with HPV-Related and HPV-Unrelated Oropharyngeal Cancer.

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV- OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV- patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV- patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV- and HPV+ OPC patients.

Clinicopathological characteristics of breast cancer patients with NOD2 mutation according to age.

INTRODUCTION: The purpose of the present study was to characterise patients with breast cancer (BC) and NOD2-mutation (age ≥ 50 years) according to their clinicopathological factors or family history. Patients aged ≥ 50 years were compared with the control group and with NOD2-mutation carriers aged < 50 years. MATERIAL AND METHODS: Prognostic factors were analysed in patients with BC with confirmed NOD2 c.3016_3017insC (n = 150) mutations. The control group was selected from patients with BC without mutations (n = 376). RESULTS: There were significant differences between NOD2-mutation carriers and the control group aged ≥ 50 years, according to HER2 overexpression (p = 0.0001), ER (-) (p = 0.007), PR (-) (p = 0.003), T1-T2 (p = 0.011), and G3 (p = 0.036). Similarly, significant differences were observed between NOD2-mutation carriers and the control group aged < 50 years, according to HER2 overexpression (p = 0.0001), ER (-) (p = 0.049), and N (+) (p = 0.038). In patients aged ≥ 50 years, family history of cancer, including BC, was observed more often in NOD2-mutation carriers compared with the control group of patients (OR = 1.66; p = 0.072, for BC in family history: OR = 2.65; p = 0.002). NOD2-mutation carriers aged ≥ 50 years had significantly less frequent G3 (p = 0.004) and HER2 overexpression (p = 0.043) compared with patients with NOD2 mutation aged < 50 years. CONCLUSIONS: The presence of the NOD2 mutation is not only characteristic of younger patients but also in patients > 50 years of age. In NOD2-mutation carriers aged ≥ 50 years, the presence of larger tumour size, G3, or HER2 overexpression were lower compared with younger patients with NOD2 mutation.

Circulating HPV16 DNA may complement imaging assessment of early treatment efficacy in patients with HPV-positive oropharyngeal cancer.

BACKGROUND: Early detection of treatment failure may improve clinical outcome and overall survival in patients with head and neck cancer after first-line treatment. Circulating cell-free HPV16 DNA (cfHPV16 DNA) was evaluated as a possible complementary marker to radiological assessment of early response in patients with HPV-related oropharyngeal cancer (OPC) after radiotherapy alone or combined with chemotherapy. METHODS: The study included 66 patients with HPV-related OPC receiving radical radiotherapy alone or in combination with chemotherapy. cfHPV16 DNA was assessed in the blood of all patients before treatment using TaqMan-based qPCR. Subsequent analysis of cfHPV16 DNA was performed 12 weeks after treatment completion, along with radiological assessment of early treatment results. RESULTS: Complete (CRR) and incomplete radiological response (IRR) was found in 43 (65%) and 23 (35%) patients respectively. cfHPV16 DNA was present in 5 (28%) patients with IRR, while only in 1 (4%) with CRR. Three of five patients with IRR that were positive for cfHPV16 DNA exhibited histopathologically confirmed local or regional treatment failure, and other two developed distant metastases. None of the patients with negative cfHPV16 DNA presented disease failure. CONCLUSION: The post-treatment assessment of cfHPV16 DNA in patients with HPV-related OPC may be used as a complementary biomarker to conventional imaging-based examinations for early identification of treatment failure.

Prognostic Value of the Neutrophil-Lymphocyte, Platelet-Lymphocyte, and Monocyte-Lymphocyte Ratios in Male Breast Cancer Patients.

BACKGROUND: The aim of the present study was to assess the blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) as prognostic factors in male breast cancer (BC) patients. METHODS: A retrospective analysis of 38 male BC patients who were treated at the Institute of Oncology (Gliwice, Poland) between January 2005 and December 2018 was performed. The prognostic value (in terms of overall survival [OS]) of the pretreatment PLR, NLR, and MLR was assessed by univariate analysis. RESULTS: We observed a tendency towards worse OS among male BC patients with lymph node metastases (N+) (5-year OS: 43.5 vs. 73.9%; p = 0.087), a greater tumor size (T4 vs. T1 + T2) (42.0 vs. 70.5%; p = 0.061), and a negative steroid receptor status (PR-) (28.6 vs. 65.6%; p = 0.109). Patients with a family history of cancer had significantly better 5-year OS than patients without a family history of cancer (86.3 vs. 35.0%; p = 0.001). Younger male BC patients (age ≤56 years) had better 5-year OS than patients >56 years of age (82.5 vs. 42.3%; p = 0.028). The 5-year OS was lower among patients with a lower lymphocyte value (≤1.82 × 103) (29.0 vs. 75.6%; p = 0.010). There was a tendency towards worse OS among patients with a higher platelet count (>281 × 103) (4.5-year OS: 16.7 vs. 65.8%; p = 0.056). The 5-year OS was insignificantly lower in the group with NLRs >2.74 than in the group with NLRs ≤2.74 (37.5 vs. 62.8%; p = 0.078). A worse OS rate was associated with an elevated PLR (>169.1) (22.2 vs. 70.1%; p = 0.008). Similarly, there was worse OS in the group with higher MLR (>0.30) (41.8 vs. 78.3%; p = 0.025). CONCLUSIONS: The present results reveal that elevated MLRs (>0.30) and PLRs (>169.1) are associated with poor OS among male BC patients. Similarly, but insignificantly, an elevated NLR (>2.74) affected OS.

Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio in breast cancer patients.

The aim of the present study was to assess the blood the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) as prognostic factors in breast cancer (BC) patients. A retrospective analysis of 436 BC patients who were treated at COI (Gliwice, Poland) between January 2005 and June 2018 was performed. The prognostic value [overall survival (OS)] of the pre-treatment PLR, NLR and MLR was assessed by univariate and multivariate analysis. The 5-year OS was lower in the NLR >2.65 compared with that in the NLR≤2.65 group (82.5 vs. 89.6%; P=0.053), and significantly lower in the subgroup of triple-negative breast cancer (TNBC; 70.3 vs. 89.3%; P=0.034) and in patients whose tumors had an estrogen receptor-negative [ER(-)] status (66.6 vs. 83.6%; P=0.018). The 5-year OS was lower in patients with PLR >190.9 compared with that in the PLR≤190.9 group (78.7 vs. 89.4%; P=0.020). A poor OS rate associated with an elevated PLR was also observed in the subgroups with TNBC (68.2 vs. 88.5%; P=0.032) and with ER(-) status tumors (57.7 vs. 83.6%, P=0.002). An elevated MLR (>0.28) was not associated with OS time (P=0.830). Multivariate analysis revealed that the NLR and PLR were insignificant negative prognostic factors, except for the subgroup of patients with ER(-) tumors, where an elevated NLR [hazard ratio (HR)=2.40; 95% confidence interval (CI): 1.20-4.80; P=0.013] and a higher PLR (HR=2.51; 95%CI: 1.23-5.14; P=0.012) were independent prognostic factors for poor OS together with lymph node metastasis ((HR=5.47; 95%CI: 2.46-12.15; P=0.0001 and HR=4.82; 95% CI: 2.15-10.78; P=0.0001), respectively. The present results revealed that an elevated NLR (>2.65) and PLR (>190.9) are associated with poor OS in BC patients. In the ER(-) subgroup of patients, an elevated NLR and PLR were significant independent prognostic factors. However, the MLR did not affect OS.

The role of postoperative adjuvant radiotherapy in the local control in medullary thyroid carcinoma.

BACKGROUND: The value of postoperative radiotherapy in the treatment of medullary thyroid carcinoma (MTC) has not been unequivocally demonstrated. Therefore our study aimed to answer the question of whether adjuvant radiotherapy showed any impact on the risk of local recurrence and whether there were any differences in response to radiotherapy between hereditary and sporadic MTC. METHODS: A retrospective analysis involved 254 MTC patients, among them 73 patients with a hereditary disease. Two hundred and twenty-four patients, including 43 persons at high risk of local relapse, underwent only initial surgery, 18 other patients were operated due to MTC recurrences, whereas the remaining 12 patients had cytoreductive procedure or were not amenable for surgery. Radiotherapy was carried out in 132 patients. One hundred and twenty patients underwent adjuvant radiotherapy, among them 102 patients after initial surgery. The median follow up was 10 years (range 0.5-29 years). RESULTS: Local recurrence occurred in 107/254 patients, among them in 63 subjects after prior radiotherapy. The frequency of relapse showed significant, increasing trend toward higher MTC stages (p<0.001). More relapses were noticed in patients with lymph node metastases at diagnosis. Adjuvant radiotherapy was associated with a lower risk of nodal recurrence only in high-risk patients, particularly if lymph node metastases were present at MTC diagnosis. The differences between hereditary and sporadic subgroups were not significant. CONCLUSIONS: Adjuvant radiotherapy has a limited importance in MTC treatment. It should be considered in high-risk MTC patients. The presence of RET mutation does not influence the response to radiation.

Molecular characteristics of breast cancer according to clinicopathological factors.

The purpose of the present study was to evaluate the correlation between molecular factors such as BRCA1 DNA repair associated (BRCA1), checkpoint kinase 2 (CHEK2) and nucleotide binding oligomerization domain containing 2 (NOD2) gene mutations and clinicopathological factors in patients with breast cancer (BC). Prognostic factors were analyzed in BC patients with confirmed BRCA1 (n=73), CHEK2 (n=51) and NOD2 (n=31) mutations. The control group was selected from BC patients without mutations (n=392). The BRCA-associated cancer cases were significantly more often triple negative compared with sporadic cancer (62% vs. 14%; P=0.0001). Luminal B HER2-positive and HER2-positive non-luminal subtypes were observed more often in the control group (33 and 17%). The luminal A subtype was detected in 53% of CHEK2 mutation carriers and 45% of NOD2 mutation carriers. A lower histological grade was observed significantly more often in patients with CHEK2 mutations in comparison with the control group (88 vs. 69%; P=0.003). Lymph nodes without metastases were reported more frequently in NOD2 mutation carriers (74 vs. 54%; P=0.038), in BRCA1 mutations (73 vs. 54%; P=0.004) and, although not significantly, in CHEK2 mutation carriers (69 vs. 54%; P=0.071) compared with the control group. In conclusion, BRCA1 mutation was associated with TNBC and the luminal B HER2 (-) subtype. HER2-positive subtypes were characteristic of the control group. CHEK2 and NOD2 mutation carriers had a more favorable profile of prognostic factors.

The Role of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Platelets in the Prognosis of Metastatic Renal Cell Carcinoma.

OBJECTIVE(S): The aim of this analysis was to evaluate the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), platelets (PLT), and neutrophil level for their prognostic value in patients with metastatic renal cell carcinoma (mRCC). MATERIALS: We retrospectively reviewed medical records of 141 patients with mRCC (2006-2016). Univariate and multivariate analyses were performed with the Cox proportional hazards regression model. The cutoff value of NLR was "elevated" as >3.68 and the PLR cutoff value was "elevated" as >144.4. RESULTS: The median PFS and OS were shorter in elevated NLR and PLR. A higher value of PLT was associated with worse median OS and higher neutrophil level with worse OS and PFS. In multivariate analysis, higher NLR (p = 0.007) and PLR (p = 0.006) were independent prognostic factors for shorter OS together with BMI ≤30 (p = 0.004), higher Fuhrman grade (p = 0.0002), lower level of hemoglobin (p= 0.010), and ZUBROD 2 (p = 0.0002). Higher PLR (p = 0.0002) was an independent negative prognostic factor for PFS together with higher Fuhrman grade (p = 0.001), higher neutrophil level (p = 0.001), and lower lymphocyte level (p = 0.013). CONCLUSION: Elevated pretreatment NLR, PLR, PLT, and neutrophil count are associated with shorter OS and PFS in patients with mRCC. NLR and PLR are independent prognostic factors for OS. However, PLR and neutrophil count are independent prognostic factors for PFS.

Nineteen-year single-center experience in 76 patients with penile cancer treated with high-dose-rate brachytherapy.

PURPOSE: To report the outcomes for 76 patients with penile cancer treated with high-dose-rate brachytherapy (HDR-BT) at a single institution. METHODS: Seventy-six patients with penile cancer treated with HDR-BT in our department between October 1998 and September 2018 were analyzed. Seventy underwent interstitial HDR-BT (fractionation dose range of 3-3.5 Gy given twice a day with an interval of at least six hours between the fractions), and six underwent superficial treatment with mold applicators (fractionation dose range of 4-7 Gy given once or twice a week). RESULTS: Median follow-up was 76 months (7-204 months). In the whole group, 22/76 local failures (28.9%) were observed: 14/76 (18.4%) local recurrences and 8/76 (10.5%) cases of persistent disease. Median time to recurrence was 24 months (9-54 months). Inguinal lymph node metastases were observed in 18/76 cases (23.7%). Distant metastases occurred in 12/76 (15.8%) cases. Patients with local recurrence and persistent disease underwent salvage penectomies, except four who refused surgery and underwent a second course of interstitial HDR-BT. Five- and 10-year cause-specific survival were 85.0% and 77.8%, respectively. Local control at 5 and 10 years was 65.6%. Five- and 10-year penile preservation were 69.5% and 66.9%, respectively. There was no G3 or G4 acute toxicity. One urethral stenosis (1.3%) occurred in a patient with a T3 tumor and was treated successfully with dilatation. CONCLUSIONS: HDR-BT provides good local control of penile cancer and is a good option for penis preservation therapy and in our experience achieves a penile preservation rate at 10 years of 66.9%.

BRCA1 mutation in breast cancer patients: Analysis of prognostic factors and survival.

The presence of BRCA1 mutations is associated with an increased risk of breast and ovarian cancer. The present study compared clinicopathological characteristics and overall survival (OS) of hereditary and sporadic breast cancer. Using data collected from a previous study conducted between 2007-2016 at the Maria Sklodowska Curie Cancer Center and Institute of Oncology (Gliwice, Poland), the prognostic factors and survival in 60 breast cancer mutation carriers were analyzed. A control group was selected from the breast cancer patients without BRCA mutations (n=386). BRCA mutation carriers had significantly worse survival when compared with non-carriers (P=0.017). The 10-year OS rate was 78.0% for all analyzed groups: 65.9% for BRCA mutation carriers and 81.1% for non-carriers. In the univariate analyses, BRCA mutation carriers had a significantly higher risk of mortality in comparison to non-carriers [hazard ratio (HR)=1.87; 95% confidence interval (CI) 1.08-3.25]. Increased tumor size (HR=3.64), lymph node metastases (HR=2.45) and higher histological grade (HR=2.84) were significant factors for worse OS. Positive estrogen receptor status was associated with a better OS (HR=0.49, P=0.022). Age ≤40 years (HR=0.48, P=0.081) was an insignificantly favorable factor. The 10-year survival rate was significantly decreased in patients with BRCA1 mutation. Therefore, negative factors for OS in mutation carriers included lymph nodes metastases, negative steroid receptor status and increased tumor size.

Checkpoint Kinase 2 (CHEK2) Mutation in Renal Cell Carcinoma: A Single-Center Experience.

Renal cell carcinoma (RCC) occurs in sporadic and heritable forms. Genetic mutations have been identified as risk factors in 1-2% of RCC. The aim of this study was to evaluate I157T and CHEK2*1100delC mutations of checkpoint kinase 2 (CHEK2) gene in RCC. Medical records of 40 clear cell RCC patients who had genetic tests and consultation at the Genetic Outpatient Clinic, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, were reviewed retrospectively. Mutation profile was assessed by ASA-PCR and RFLP-PCR techniques. Only three female patients had CHEK2 mutation (I157T). No CHEK2*1100delC was observed in any of the patients. These tumors were N0, and two were Grade 3. One showed capsular infiltration. No blood vessel infiltration or metastases was observed. Overall, RCC from patients with CHEK2 mutation did not display any special characteristics when compared with those without the mutation. While no association between CHEK2 mutation and RCC could be established, all three patients with CHEK2 mutation developed second neoplasms many years after first diagnosis. Further studies, especially regarding CHEK2 mutation as a predictive factor for second neoplasm in RCC patients, are warranted.

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).

Interstitial high-dose-rate brachytherapy in locally advanced and recurrent vulvar cancer.

PURPOSE: The aim of the study was to report our experience with high-dose-rate interstitial brachytherapy (HDR-ISBT) in locally advanced and recurrent vulvar cancer. MATERIAL AND METHODS: Between 2004 and 2014, fourteen women with locally advanced or recurrent vulvar cancer were treated using HDR-ISBT in our Centre. High-dose-rate interstitial brachytherapy was performed as a separate treatment or in combination with external beam radiotherapy (EBRT) (given prior to brachytherapy). RESULTS: Patients were divided into: group I (n = 6) with locally advanced tumors, stages III-IVA after an incisional biopsy only, and group II (n = 8) with recurrent vulvar cancer after previous radical surgery. In group I, median follow up was 12 months (range 7-18 months); 1-year overall survival (OS) was 83%. Transient arrest of cancer growth or tumor regression was noticed in all patients but 4/6 developed relapse. Median time to failure was 6.3 months (range 3-11 months). The 1-year progression-free survival (PFS) was 33%. In group II, median follow up was 28 months (range 13-90 months). The 1-year and 3-year OS was 100% and 80%, respectively. The arrest of cancer growth or tumor regression was achieved in all patients. In 4/8 patients neither clinical nor histological symptoms of relapse were observed but 4/8 women experienced relapse. Median time to failure was 31 months (range 13-76 months). The 1-year and 3-year PFS was 100% and 62.5%, respectively. Two patients (14.3%) in group II had severe late toxicity (G3). CONCLUSIONS: High-dose-rate interstitial brachytherapy is a well-tolerated treatment option in selected patients with advanced or recurrent vulvar cancer. It is a safe and effective treatment modality for advanced and recurrent vulvar cancer, yielding good local control with acceptable late treatment related side effects. In our study, patients with recurrent vulvar cancer had better results in HDR-ISBT treatment, probably because of the smaller tumor volume. This hypothesis should be verified in a larger group of patients.