Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer.

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25-30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in patients with extensive-stage small cell lung cancer treated with atezolizumab in combination with chemotherapy.

Atezolizumab is now the standard treatment for extensive-stage small cell lung cancer (ES-SCLC). Herein, we investigated the prognostic role of inflammatory markers in patients treated with atezolizumab plus chemotherapy and evaluated the efficacy and safety of adding atezolizumab to chemotherapy for patients with ES-SCLC and prognostic and predictive factors as a real-life experience. This retrospective study included 55 patients who received front-line atezolizumab with etoposide plus platin regimen for ES-SCLC. We analyzed the survival outcomes and factors that may predict response and survival. The objective response rate (ORR) was 81.8%. At a median follow-up of 23.5 months, the median progression-free survival (PFS) time was 10.8 months, and the median overall survival (OS) time was 15.2 months. In univariate analysis for PFS, limited-stage disease at the time of diagnosis, the presence of prophylactic cranial irradiation (PCI), the presence of liver metastasis, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were found to be prognostic factors (P = .041, P = .034, P = .031, P = .004, and P = <.001, respectively). In other words, while the median PFS time was 14.1 months in patients with PLR ≤ 135.7, it was 7.5 months in patients with > 135.7. Similarly, median PFS was 14.9 months in patients with NLR ≤ 3.43, while it was 9.6 months in patients with > 3.43. Univariate analysis for OS revealed that limited stage at the time of diagnosis, NLR and PLR were significant prognostic indicators (P = .01, P = .006, and P = .007, respectively). Median OS time for patients with both NLR ≤ 3.43 and PLR ≤ 135.7 was significantly better than that of patients with NLR > 3.43 and PLR > 135.7 (16.9 vs 11.3 and 16.9 vs 11.5 months, respectively). Logistic regression analysis demonstrated that PLR was an independent significant predictive factor for the response to atezolizumab plus chemotherapy (OR: 0.07, P = .028). The patients with PLR ≤ 135.7 were significantly good responders to atezolizumab plus chemotherapy treatment. Real-life data demonstrated a significant correlation between survival and NLR and, PLR in ES-SCLC patients treated with atezolizumab. In addition, PLR was a significant predictive indicator of response to atezolizumab plus chemotherapy.

Diffuse Leptomeningeal Glioneuronal Tumors: A Case Series of Five Patients with Parenchymal Forms and an Analysis of the Diagnostic Challenges, Treatment Options and Outcomes.

BACKGROUND: Diffuse leptomeningeal glioneuronal tumors (DL-GNT) are rare glioneuronal neoplasms with oligodendroglioma-like cells. These tumors can present as a dominant intracranial mass or as a solitary spinal cord mass without leptomeningeal involvement. In this study, we aimed to determine the magnetic resonance imaging and histopathological features, treatment modalities, and clinical outcomes of the parenchymal forms of DL-GNTs. METHODS: This is a retrospective three-center case series study of 5 patients with a confirmed parenchymal form of DLGTs, out of which 4 patients were adults. Brain and spinal cord MR imaging were performed in all patients at either 1.5 or 3T. The patients' age ranged from 5 years to 50 years with a mean age of 27.6 years at presentation. RESULTS: Four of the tumors were located in the frontal lobe, and one in the tectum. They were usually solid-cystic enhancing tumors as the other mixed neuronal-glial tumors. All of the tumors had an extension to the superficial surface of a cerebral hemisphere. One had systemic bone metastases. The clinical signs and symptoms of the parenchymal form varied based on the location of the mass, in contrast to the leptomeningeal form associated with hydrocephalus. In one case, the tumor's initial grade was defined as intermediate. The initial histopathology of the two cases was low-grade and no upgrade occurred in the follow-up period. In two cases, although the tumors were low grade initially, they progressed to an anaplastic form in the follow-up period. CONCLUSION: The parenchymal form of DL-GNTs is common in adults. Extension to the superficial surface of a cerebral hemisphere is a distinctive imaging feature. Systemic osseous metastasis may occur. Due to the presence of common histopathological features, including the biphasic composition of glial and neuronal cell elements and oligodendroglioma-like cells, a proposed classification approach might be more beneficial for the histopathological and imaging description, and management of the glioneuronal tumors with oligodendroglioma-like features.

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group.

PURPOSE: Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. METHODS: This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. RESULTS: A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. CONCLUSION: This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.

Programmed Cell Death Ligand 1 Expression in Cytological and Surgical Non-Small Cell Lung Cancer Specimens in Association with EGFR Mutation and Overall Survival: A Single-Institution Experience.

OBJECTIVE: The aim of this study was to evaluate programmed cell death ligand-1 (PD-L1) expression and the relationship between driver mutations and survival analysis in advanced-stage non-small cell lung carcinoma (NSCLC). MATERIAL AND METHOD: A total of 122 advanced-stage NSCLC patients were included in this retrospective study. The patients were diagnosed based on cytological examination and histopathological analysis of biopsy or resection material that had undergone at least 1 molecular analysis. The expression of PD-L1 in tumors and tumor-infiltrating lymphocytes (TIL) was scored and compared with age, sex, organ, biopsy method, tumor subtype, driver mutation status, and overall survival data. RESULTS: There was no statistically significant difference between PD-L1-positivity and age, gender, location, pattern, or pathological diagnosis of the type of sample. When the threshold value for PD-L1 IHC evaluation was accepted as ≥1% and ≥50%, the rate of positivity was 19.7% and 7.4%, respectively. CONCLUSION: Since there is a wide range of positivity rates reported in the literature, we could not reach a conclusion as to whether the PD-L1-positivity rate we observed was high or low. There is a need for comparative studies where the technique, clones, threshold values, and phases are homogenized. There is an inverse correlation between the EGFR-mutant population and PD-L1 positivity. In terms of overall survival, no relationship was found between PD-L1 positivity, the presence of TIL, and EGFR mutation status.

Prognostic value of expression levels of miR-148a, miR-152 and HLA-G in colon cancer.

Aberrant expression of human leukocyte antigen G (HLA-G), an immunosuppressive molecule, has been observed in various cancer types. The exact mechanism of HLA-G expression is unclear. HLA-G expression is associated with low expression levels of microRNA (miR)-148a and miR-152. To the best of our knowledge, the prognostic value of the expression levels of miR-148a, miR-152 and HLA-G has not been investigated in colon cancer. The aim of the present study was to investigate the relationship between the presence of HLA-G molecules and the expression levels of miR-148 and miR-152 in colon cancer. In addition, the association of both HLA-G and miR expression with survival results and clinicopathological data was determined. An immunohistochemical method was used for detection of HLA-G expression in the tumor tissues and adjacent healthy tissues of 108 patients with colon cancer. Reverse transcription-quantitative PCR was used for miR analysis. HLA-G was expressed in 82 (75.9%) of the cancer samples, and there was no staining in normal tissues. HLA-G expression >20%, which was found in 41.7% (45/108) of the patients with colon cancer, was significantly positively associated with patient survival (P=0.039). Additionally, miR-148a levels were lower in the tumor tissues compared with the adjacent healthy tissues. No differences were found for miR-152 expression. In addition, mir-148a levels were found to be significantly lower (P=0.001) in HLA-G-positive tumor tissues than HLA-G-negative tumor tissues, but no such relationship was found for miR-152 levels. The presence of HLA-G expression was associated with poor survival outcomes. HLA-G is one of the prognostic factors in colon cancer, and decreased miR-148a expression in colon cancer tissues may be associated with HLA-G-mediated carcinogenesis.

Isolated Pituitary Metastasis of Renal Cell Carcinoma: A Case Report and Systematic Review of the Literature.

BACKGROUND: Isolated pituitary gland metastasis is an extremely rare event in renal cell carcinoma. We present a unique case of isolated pituitary metastasis of renal cell carcinoma and a systematic review of literature on it. CASE REPORT: In this case, an abdominal ultrasound in an asymptomatic 51-year-old female patient showed a mass in her left kidney. Radical nephrectomy was performed and the tumor was diagnosed as a stage 1 clear cell carcinoma. Throughout the 3 months of the follow-up period, the patient started complaining of visual disturbances and headaches. A pituitary mass was found on brain magnetic resonance imaging and was suspected to be a macroadenoma. Surgical resection of the tumor was performed and the final pathological diagnosis was made as a pituitary metastasis of the renal cell carcinoma. After surgery, radiotherapy with sunitinib, a receptor tyrosine inhibitor, was performed. CONCLUSION: The clinical symptoms are usually related to the mass effect of the tumor and anterior pituitary involvement. Most of the cases mimic pituitary macroadenoma on MRI. The most preferred treatment combination is surgery and radiotherapy. We recommend adding sunitinib to this combination. This illustrative case and those found in a systematic review of the literature highlight the importance of histopathologic diagnosis and appropriate management since isolated pituitary metastasis is challenging to preoperative diagnosis.

A Successful Model for an Introductory Oncology Teaching Conference and Its Impact on Preclinical and Clinical Medical Students.

PURPOSE: Oncology education at medical schools is often fragmented, under-represented, and nonstandardized. Medical students lack essential knowledge, skills, and attitudes necessary for them to provide optimal primary care to patients with cancer upon graduation. METHODS: In this study, we designed and assessed the impact of a compact oncology teaching conference on medical students. The conference covered topics in cancer biology, public health, diagnosis, patient management, treatment, and communication skills. Medical students completed voluntary presurveys and postsurveys regarding their perceived knowledge, attitudes, and perspectives. The event was promoted by student groups, particularly our ASCO Oncology Student Interest Group, and took place online. RESULTS: A total of 228 responses from medical students representing 50 universities were analyzed. We revealed significant baseline confidence and perceived knowledge deficits especially in diagnosis and patient management, and treatment modalities. Our conference positively affected self-assessed knowledge acquisition among students, with the most pronounced differences seen in diagnosis and patient management (2.51 ± 1 v 3.87 ± 0.81) and treatment modalities (2.54 ± 0.96 v 3.79 ± 0.88), P < .001. Students believed the program was beneficial, felt more confident in applying their knowledge in the clinic and in delivering bad news, and were more interested in pursuing oncology-related fields, P < .001. CONCLUSION: We demonstrated that a compact teaching conference resulted in significant improvements in students' confidence and perceived knowledge about oncology. Our successful teaching model can be adapted and implemented at medical schools globally. Development and evaluation of teaching programs are important to urgently reform undergraduate medical education in oncology.

Platelet to lymphocyte ratio is associated with tumor localization and outcomes in metastatic colorectal cancer.

ABSTRACT: The aim of this study was to investigate the predictive and prognostic value of PLR, and the relationship between PLR and tumor localization.A total of 229 patients with de-novo metastatic CRC were retrospectively analyzed. The cutoff value for PLR was defined by the receiver operating characteristic (ROC) curve analysis and threshold value of 196.5 as best cut-off value was found.The higher rate of BRAF mutation was significantly detected for patients with PLRhigh (> 196.5) compared to those with PLRlow (≤196.5) (P = .001). PLR was significantly higher in tumors located on the right colon (P = .012). PLR, tumor localization, the presence of surgery for primary tumor, the presence of curative surgery, the presence of metastasectomy for progression-free survival (PFS) and PLR, gender, BRAF mutation, tumor localization, the presence of surgery for primary tumor, the presence of metastasectomy for overall survival (OS) were found to be prognostic factors by univariate analysis. Multivariate analysis showed that PLR, the presence of curative surgery and the presence of metastasectomy for both PFS and OS were found to be independent prognostic factors. Moreover, a logistic regression analysis indicated that PLR and tumor localization were found to be an independent factors for predicting response to systemic treatment (P < .001 and P = .023 respectively).Our results showed that pretreatment PLR was readily feasible and simple biomarker predicting response to treatment and survival, in addition it was significantly associated with tumor localization.

Magnetic resonance imaging criteria for prediction of isocitrate dehydrogenase (IDH) mutation status in patients with grade II-III astrocytoma and oligodendroglioma.

BACKGROUND: IDH mutation status is an important prognostic marker for glial tumors, which is detected immunohistochemically after surgery. Since this method is invasive, easy and noninvasive magnetic resonance imaging (MRI) methods have recently been used in predicting the IDH mutation status. However, there is currently no standard MRI technique to predict IDH mutation. We analyzed the value of conventional MRI to predict IDH mutation and its effect on survival among grade II-III astrocytoma and oligodendroglioma patients. MATERIAL AND METHODS: We included WHO grade II-III astrocytoma and oligodendroglioma patients who underwent surgery at Bahcesehir University Goztepe Medical Park Hospital. All patients were analyzed according to their immunohistochemical IDH mutation status. Preoperative conventional MRI studies with respect to their location, diffusion restriction, contrast enhancement, calcification and hemorrhage on susceptibility-weighted image (SWI) or T2*- weighted imaging (T2*WI), and T2 -FLAIR mismatch properties were retrospectively assessed by a neuroradiologist. The relation between MRI characteristics and IDH mutation was analyzed using a chi-square test. The sensitivity and specificity of radiological IDH mutation were determined by ROC analysis. The impact of IDH mutation on survival was also analyzed by Kaplan-Meier tests. RESULTS: IDH mutation was found to be positive in 82.5% of tumors histopathologically and 54.4% radiologically. The sensitivity and specificity were 63.8% and 90%, respectively (Area under the curve/AUC = 0.369, p = 0.08). IDH wild gliomas were predominantly diffusion-restricted tumors. IDH mutant tumors were less likely to have contrast enhancement and had lower grades compared to the IDH wild tumors. The median survival time could not be reached and the overall survival was not related to any tumor characteristics or IDH mutation. CONCLUSIONS: Conventional MRI predicts IDH-mutation status in Grade II-III astrocytoma and oligodendroglioma. Contrast-enhancement and restricted diffusion were strongly associated with grade III astrocytoma and oligodendroglioma, IDH-wild type. Location, T2-FLAIR mismatch, and SWI did not contribute to making a decision on the IDH mutation status. There was no significant difference between the survival times of patients and their IDH status.

Abdominal Variant of Lemierre's Syndrome in a Patient with Pancreatic Adenocarcinoma.

Lemierre's syndrome is an illness characterized by internal jugular vein thrombophlebitis related to infectious agents, primarily Fusobacterium necrophorum. These bacteria, residing in both the oropharynx and the gastrointestinal tract, may lead to pylephlebitis, a serious condition that could result in the development of hepatic abscesses. This manifestation of the disease is regarded as the abdominal variant of Lemierre's syndrome. Patients with gastrointestinal malignancies, especially those who undergo surgeries, are susceptible to the abdominal variant of Lemierre's syndrome. Timely diagnosis is required to avoid the life-threatening complications of the abdominal variant of Lemierre's syndrome. Diffusion-weighted magnetic resonance imaging (MRI) might be very useful in differentiating this disease from liver metastasis in patients with malignancies. Radiologists and clinicians need to be aware of this challenging condition to prevent misdiagnosis, since prompt treatment is often lifesaving.

The relationship between positron emission tomography-computed tomography imaging and histopathological features of thyroid incidentalomas detected during follow-up for primary malignancy.

AIM OF THE STUDY: While the rate of thyroid incidentaloma detected on positron emission tomography (PET) was reported as 4%, the malignancy rate was 14%-50%. We evaluated the thyroid nodules which were detected by PET-computerized tomography (CT) in cancer patients and analyzed the pathological results of those thyroid nodules diagnosed by fine needle aspiration biopsy (FNAB) and their correlation with the maximum standardized uptake (SUVmax) value and PET imaging features. MATERIALS AND METHODS: FNAB were performed for 40 thyroid incidentalomas. We analyzed the relationship between the histopathological findings and radiological features by Pearson's correlations and Chi-square-Fisher's exact tests to evaluate the factors associated with SUVmax. RESULTS: The median SUVmax values were 5.4 for thyroid nodules. Totally, 14 malignancies were detected by FNAB (35%).The sensitivity and specificity of SUVmax value for diagnosis of malignancy were 87.5% and 52%, respectively. Positive and negative predictive values were 36.8% and 92.8%. The most common malignant and benign pathologies were classic variant papillary carcinoma and benign colloidal nodule. The median SUVmax was the higher in colon cancer thyroid metastasis and oncocytic neoplasia (SUVmax 14.5 and 13.6, respectively). Histopathological type was not related with nodule size but positively associated with categorical SUVmax(r = 0.318, P = 0.04) and negatively correlated with both the density of the thyroid nodule in PET-CT (r = -0.0042, P = 0.01) and density of nodule in ultrasound (USG) (r = -0.305, P = 0.05). Margin of the thyroid nodule in USG (P = 0.007) and internal component of the nodule in PET (P = 0.03) were found to be important factors to differentiate benign or malignant lesion. CONCLUSION: If the thyroid nodule is detected with flouro-2-deoxy-D-glucose uptake, to differentiate benign nodule from malignant, cytological examination is noteworthy to diagnose the more aggressive type of thyroid nodule and also thyroid metastasis from primary cancer.

Primary small cell carcinoma of the breast: report of seven cases and review of the literature.

AIMS AND BACKGROUND: The aim of the study was to analyze the clinicopathological characteristics, treatment modalities, and clinical outcome of patients with primary small cell carcinoma of the breast. METHODS: Fifty-three cases of primary small cell carcinoma of the breast were identified; 7 cases in this series and 46 from the English-language medical literature. RESULTS: There were 52 females and 1 male. The mean age was 53 years. Tumor size ranged from 1 to 18 cm (mean, 4.53). Axillary node metastasis was present in 61.7%. Only one patient had distant metastases at presentation. The presence of hormone receptors was reported in 24.5% of the tumors. Modified radical mastectomy was the most common surgical procedure and was performed in 50.9% of the patients. Adjuvant radiotherapy was administered to 39.6% of the patients, and 69.8% underwent chemotherapy. Thirteen percent of patients received adjuvant tamoxifen therapy. The mean follow-up was 20.75 months (range, 3-60), and 10 of 53 cases (18.9%) died of metastatic disease. CONCLUSIONS: The prognosis of primary small cell carcinoma of the breast largely depends on the initial stage of the disease. Multimodality treatment including surgery, radiotherapy and chemotherapy seems to be the most appropriate strategy for early disease. Chemotherapy is usually unsuccessful in treating metastatic disease.