Histopathological Features Predicting Neuroendocrine Morphology in Primary Breast Tumors: A Retrospective Analysis.

Objective: Neuroendocrine neoplasms of primary breast tumors are rare compared to locations, such as the respiratory system and gastrointestinal system, where they are frequently observed. The diagnostic criteria for primary neuroendocrine tumors of the breast have been changed since first description. Morphological and immunohistochemical features helpful in their diagnosis, which vary due to the heterogeneous nature of these tumors, are highlighted in this retrospective study. The purpose was to determine specific histopathological features that can identify neuroendocrine morphology in primary breast tumors. Materials and Methods: Cases diagnosed with invasive breast carcinoma from resection materials in a single center between 2011 and 2022 and in which neuroendocrine markers were investigated were included. Demographic information, initial histopathological diagnosis, presence of tumor in another organ, tumor location, size and surgical details of the cases were obtained from the hospital database and pathology reports. The slides were re-evaluated in terms of tumor growth pattern, cribriformity, tubule formation, nuclear features, prominence of nucleoli, palisading and basal location of nuclei, presence of grooves, cytoplasmic features and evidence of cytoplasmic border. Results: The presence of basally located nuclei, absence of tubule formation, inconspicuous nucleoli, fine nuclear chromatin, granular cytoplasm and inconspicuous cytoplasmic borders were frequent findings in tumors with neuroendocrine features (p<0.05). These features may help differentiate primary breast tumors with neuroendocrine features from other breast carcinomas. Conclusion: The histopathological features that are different from the specific features seen in classical neuroendocrine tumors, the absence of specific clinical and radiological findings, the inability to study neuroendocrine markers in every laboratory and the need to prove that the breast tumor is not a metastasis all create diagnostic difficulties for primary breast neuroendocrine neoplasms. We believe that the results of this study may help diagnose and identify more specific histomorphological features that help determine neuroendocrine morphology in primary breast tumors.

Immunotherapy experience in sinonasal NUT midline carcinoma, case report.

NUT midline carcinoma (NMC) is an aggressive malignant neoplasm arising from midline structures. Although it is classified as a rare disease, the pathological nonspecific appearance as undifferentiated/poorly differentiated carcinoma and the difficulty in making the definitive diagnosis are probably the reasons for the underdiagnosis; the disease is thought to be more prevalent. There is no standard treatment for the disease. The disease shows a poor response to chemotherapy and radiotherapy, and patients' survival is poor. We present a case of sinonasal NMC treated with chemotherapy and immunotherapy in first-line, which is the first in the literature. The patient presented with metastatic disease and received cisplatin-fluorouracil-docetaxel-pembrolizumab treatment. The tumor's PD-L1 expression was 10%, evaluated by tumor proportion score. The response to the therapy was poor, and the patient died of disease progression 5.4 months after the diagnosis. The efficacy of immunotherapy in NMC is not known. More reports are needed to draw conclusions.

The effect of two different types of music played to cancer patients during chemotherapy on anxiety, nausea, and satisfaction levels.

PURPOSE: To investigate the effect of two different types of music on anxiety, nausea, and satisfaction levels in cancer patients receiving chemotherapy (CT) for the first time. METHODS: The study was conducted as a single-blind, pre-test, post-test, three-group randomized controlled trial in an outpatient CT unit between August 2022 and February 2023. A simple (computer-based) and stratified (age and gender) randomization method was used to assign 75 patients to the relaxing music group (RMG), Turkish classical music group (TCMG), and control group (CG) (n = 25 each). The primary outcome was the change in anxiety levels measured by Spielberger's State Anxiety Inventory before (T0) and after (T1) CT session. Secondary outcomes were the change in the severity of nausea from T0 to T1 and the level of satisfaction at T1. RESULTS: The groups were similar in terms of baseline sociodemographic and health-related characteristics. Anxiety levels were lower than the baseline in RMG and TCMG in comparison to CG, and repeated measures analysis showed a significant group × time interaction (p = 0.001, F = 210.221, η2 = 0.745). Nausea severity increased from T0 to T1 for CG but decreased for RMG and TCMG with a significant group × time interaction (p = 0.001, F = 100.785, η2 = 0.583). The satisfaction level was significantly higher in TCMG than in CG and RMG (8.64 ± 0.95 vs. 7.88 ± 0.72, and 7.00 ± 0.70, respectively). CONCLUSION: Music may be an effective non-pharmacologic option to relieve patients' anxiety and nausea during first-time CT. Larger, multicenter studies evaluating the long-term effect of music are needed to confirm these findings. TRIAL REGISTRATION: clinicaltrials.gov (NCT05687838)/2022-13/18.

Early thrombocytopenia predicts longer time­to­treatment discontinuation in trastuzumab emtansine treatment.

Thrombocytopenia is a characteristic adverse event of trastuzumab emtansine (T-DM1), one of the essential treatment options for human epithelial growth factor receptor 2 (HER2)-positive breast cancer. The present study investigated the predictive value of thrombocytopenia for time-to-treatment discontinuation (TTD) in patients receiving T-DM1 for advanced-stage HER2-positive breast cancer. The present observational study enrolled 138 patients who received T-DM1 at six oncology centers from January 2016 to December 2021. Univariate and multivariate Cox regression analyses were performed to determine the factors affecting TTD. The median age of patients was 50 years (range, 26-83). The median number of T-DM1 cycles was 9 (range, 2-58), the overall response rate was 50.0% and the disease control rate was 69.6%. At a median follow-up time of 19.3 months, the median TTD was 9.5 months [95% confidence interval (CI), 7.3-11.7], and the median overall survival was 28.2 months (95% CI, 19.2-37.2). Thrombocytopenia during treatment was observed in 39% of all patients, and 66.7% of these patients experienced early thrombocytopenia (in the first four treatment cycles). Multivariate analysis revealed that the independent factors for TTD were hormone receptor status [hazard ratio (HR), 1.837; 95% CI, 1.249-2.701; P=0.002], Eastern Cooperative Oncology Group performance status score (HR, 3.269; 95% CI, 1.788-5.976; P<0.001) and thrombocytopenia during treatment (HR, 0.297; 95% CI, 0.198-0.446; P<0.001). Patients with early thrombocytopenia had a significantly longer TTD of 17.3 months (95% CI, 11.8-22.8) compared with 7.6 months (95% CI, 5.8-9.4) for patients without early thrombocytopenia (P<0.001). The results of the present study indicated that patients with early thrombocytopenia had improved survival outcomes compared with those without. Thus, maximum benefit from T-DM1 treatment may be achieved by confirming the predictive role of thrombocytopenia in T-DM1 treatment in prospective studies and large-scale cohorts.

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey.

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.

The effects of Ankaferd hemostat on preventing oral mucositis in colorectal cancer patients receiving chemotherapy.

INTRODUCTION: New agents are introduced each day to be used in the prevention and treatment of mucositis in cancer treatment. One of those agents is the Ankaferd hemostat. Ankaferd hemostat has pleiotropic effects and anti-infective characteristics in tissue healing. METHODS: The study was designed as a randomized controlled experimental study. The sample of the study comprised a total of 66 patients (33 patients in the Ankaferd hemostat group and 33 patients in the sodium bicarbonate group) with colorectal cancer who received FOLFOX combination chemotherapy treatment in the first cycle of chemotherapy to prevent mucositis. Participants who met the criteria were randomly assigned to the groups. Before the patient received chemotherapy, ECOG performance score and Oral Mucositis Grading Scale were applied on the 7th day and 15th day. The Ankaferd hemostat group brushed teeth at least twice a day for 2 min and gargled with Ankaferd hemostat twice for 2 min for 2 weeks. The sodium bicarbonate group brushed teeth at least 2 min a day and gargled with sodium bicarbonate 4 times for 2 min for 2 weeks. The Consolidated Standards of Reporting Trials diagram was used to illustrate the randomization of patients. RESULTS: When the Ankaferd hemostat group is compared with the sodium bicarbonate group, there is a significant difference in favor of the Ankaferd hemostat group in the mucositis grade on the 7th day and 15th day after chemotherapy (p < 0.05). In the binary logistic regression analysis, among the factors affecting the formation of mucositis on the 7th day, only neutrophil and thyroid-stimulating hormone (TSH) were included in the model, while only the TSH variable is statistically significant. CONCLUSIONS: It was determined that Ankaferd hemostat is effective in preventing oral mucositis due to chemotherapy in adult patients diagnosed with colorectal cancer. In addition, it has been suggested to conduct new studies on the effectiveness of Ankaferd hemostat in the prevention of mucositis in different groups. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ID: NCT05438771, Date: 25.06.2022).

Platin­based chemotherapy does not improve survival in patients with non­metastatic resected typical carcinoid tumors.

Chemotherapy is controversial in non-metastatic typical carcinoid (TC) tumors. Therefore, it was aimed to evaluate the impact of platin-based chemotherapy on the survival of patients with lung TC. The medical records of patients who underwent surgical resection for non-metastatic TC from 2002 to 2020 at our institution were retrospectively reviewed. Multivariate regression analysis was performed for chemotherapy and prognostic factors in disease-free survival (DFS) in 72 patients. The pathological stages of patients were as follows: 73.6% of the patients were in stage I, 15.3% in stage II and 11.1% in stage III. A total of 5 patients (6.9%) received platin-based chemotherapy and 6 patients (8.3%) had recurrences. The DFS rates at 12, 36 and 60 months were 98.5, 95.1 and 92.5%, respectively. Log-rank testing showed that patients who received chemotherapy and had stage III disease had shorter DFS (P=0.021 for chemotherapy and P<0.001 for stage). However, multivariate analysis revealed that the pathological stage was the only statistically significant factor affecting DFS (P=0.016). Platin-based chemotherapy did not improve DFS, and the eighth edition of TNM (tumor, nodes, metastases) staging did have prognostic value for patients with non-metastatic TC. Although resection has satisfying long-term outcomes, studies on new agents are needed to decrease the recurrence rate, particularly in patients with stage III disease.

Safety and efficacy of trifluridine/tipiracil in previously treated metastatic colorectal cancer: PRECONNECT Turkey.

Background: The efficacy and safety of trifluridine/tipiracil (FTD/TPI) for third-line treatment of metastatic colorectal cancer have been demonstrated. The authors present the Turkish post hoc analysis of the PRECONNECT study. Methods: An international, multicenter, single-arm, open-label, phase IIIb trial evaluating FTD/TPI in patients with ≥2 previous lines of chemotherapy for metastatic colorectal cancer was conducted. The primary end point was safety. Results: In this Turkish cohort (n = 100; eight centers), the most frequent treatment-emergent adverse event was neutropenia (48%). Median progression-free survival was 3.0 months; disease control rate was 36%; quality of life remained stable. Conclusion: Outcomes with FTD/TPI in Turkey are consistent with previous studies and confirm the efficacy and safety of FTD/TPI treatment in the third-line setting. Clinical Trial Registration: NCT03306394 (ClinicalTrials.gov).

Primary Surgery with Systemic Therapy in Patients with de Novo Stage IV Breast Cancer: 10-year Follow-up; Protocol MF07-01 Randomized Clinical Trial.

BACKGROUND: The aim of this randomized clinical trial was to evaluate the overall survival (OS) data of patients diagnosed with de novo stage IV breast cancer (BC) who received locoregional treatment (LRT) over a 10-year follow-up. STUDY DESIGN: The MF07-01 is a 1:1 multicenter, randomized clinical trial comparing the LRT with systemic therapy (ST), where ST was given to all patients either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: A total of 278 patients were randomized and 265 patients were in the final analysis. At 10-year follow-up, survivals were 19% (95% CI 13%-28%) and 5% (95% CI 2%-12%) in the LRT group and ST group, respectively. Median survival was 46 months for the LRT group and 35 months for the ST group, and hazard of death was 29% lower in the LRT group compared with the ST group (hazard ratio [HR] 0.71; 95% CI 0.59-0.86; p = 0.0003). CONCLUSIONS: Patients with a diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 14% higher chance of OS by the end of the 10-year follow-up compared with the patients who received only ST. The longer study follow-up revealed that LRT should be presented to patients when discussing treatment options.

Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy.

Blood-based biomarkers reflect systemic inflammation status and have prognostic and predictive value in solid malignancies. As a recently defined biomarker, Pan-Immune-Inflammation-Value (PIV) integrates different peripheral blood cell subpopulations. This retrospective study of collected data aimed to assess whether PIV may predict the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in Turkish women with breast cancer. The study consisted of 743 patients with breast cancer who were scheduled to undergo NAC before attempting cytoreductive surgery. A pre-treatment complete blood count was obtained in the two weeks preceding NAC, and blood-based biomarkers were calculated from absolute counts of relevant cell populations. The pCR was defined as the absence of tumor cells in both the mastectomy specimen and lymph nodes. Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). One hundred seven patients (14.4%) had pCR. In receiver operating characteristic analysis, optimal cut-off values for the neutrophile-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte (PLR), PIV, and Ki-67 index were determined as ≥ 2.34, ≥ 0.22, ≥ 131.8, ≥ 306.4, and ≥ 27, respectively. The clinical tumor (T) stage, NLR, MLR, PLR, PIV, estrogen receptor (ER) status, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index were significantly associated with NAC response in univariate analyses. However, multivariate analysis revealed that the clinical T stage, PIV, ER status, HER-2 status, and Ki-67 index were independent predictors for pCR. Moreover, the low PIV group patients had significantly better DFS and OS than those in the high PIV group (p = 0.034, p = 0.028, respectively). Based on our results, pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR in Turkish women with breast cancer who received NAC. However, further studies are needed to confirm our findings.

Why do some patients with stage 1A and 1B endometrial endometrioid carcinoma experience recurrence? A retrospective study in search of prognostic factors.

OBJECTIVES: Endometrial endometrioid carcinoma (EEC) is the most encountered subtype of endometrial cancer (EC). Our study aimed to investigate the factors affecting recurrence in patients with stage 1A and 1B EEC. MATERIAL AND METHODS: Our study included 284 patients diagnosed with the International Federation of Gynecology and Obstetrics stage 1A/1B EEC in our center from 2010 to 2018. The clinicopathological characteristics of the patients were obtained retrospectively from their electronic files. RESULTS: The median age of the patients was 60 years (range 31-89). The median follow-up time of the patients was 63.6 months (range 3.3-185.6). Twenty-two (7.74%) patients relapsed during follow-up. Among the relapsed patients, 59.1% were at stage 1A ECC, and 40.9% were at stage 1B. In our study, the one-, three-, and five-year recurrence-free survival (RFS) rates were 98.9%, 95.4%, and 92.9%, respectively. In the multivariate analysis, grade and tumor size were found to be independent parameters of RFS in all stage 1 EEC patients. Furthermore, the Ki-67 index was found to affect RFS in stage 1A EEC patients, and tumor grade affected RFS in stage 1B EEC patients. In the time-dependent receiver operating characteristic curve analysis, the statistically significant cut-off values were determined for tumor size and Ki-67 index in stage 1 EEC patients. CONCLUSIONS: Stage 1-EEC patients in the higher risk group in terms of tumor size, Ki-67, and grade should be closely monitored for recurrence. Defining the prognostic factors for recurrence in stage 1 EEC patients may lead to changes in follow-up algorithms.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

DPYD c.1905 + 1G>A Promotes Fluoropyrimidine-Induced Anemia, a Prognostic Factor in Disease-Free Survival, in Colorectal Cancer.

Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects. Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated. Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009). Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.

The impact of Ki-67 index, squamous differentiation, and several clinicopathologic parameters on the recurrence of low and intermediate-risk endometrial cancer.

Endometrial endometrioid carcinoma (EEC) represents approximately 75-80% of endometrial carcinoma cases. Three hundred and thirty-six patients with EEC followed-up in the authors' medical center between 2010 and 2018 were included in our study. Two hundred and seventy-two low and intermediate EEC patients were identified using the European Society for Medical Oncology criteria and confirmed by histopathological examination. Recurrence was reported in 17 of these patients. The study group consisted of patients with relapse. A control group of 51 patients was formed at a ratio of 3:1 according to age, stage, and grade, similar to that in the study group. Of the 17 patients with recurrent disease, 13 patients (76.5%) were Stage 1A, and 4 patients (23.5%) were Stage 1B. No significant difference was found in age, stage, and grade between the case and control groups (p > 0.05). Body mass index, parity, tumor size, lower uterine segment involvement, SqD, and Ki-67 index with p<0.25 in the univariate logistic regression analysis were included in the multivariate analysis. Ki-67 was statistically significant in multivariate analysis (p = 0.018); however, there was no statistical significance in SqD and other parameters. Our data suggest that the Ki-67 index rather than SqD needs to be assessed for recurrence in patients with low- and intermediate-risk EEC.

Efficacy of chemotherapeutics in classic and non-classic Kaposi sarcoma: A single-center retrospective real-world data.

Kaposi sarcoma is a rare disease and there is a gap in the literature about which chemotherapeutics should be applied, especially for the classical type. We aimed to present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 Kaposi sarcoma (KS) patients treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics, and the chemotherapeutic agents administered to the 16 KS patients diagnosed in our center and treated with chemotherapy, based on the medical records obtained. The median age, gender, type of KS, site of involvement, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4-85.8 years). Among the patients, 1 had immunosuppression-related KS, 4 had AIDS-related KS, and 11 had classical KS. In the first-line cytotoxic therapy, 7 patients received pegylated-liposomal doxorubicin (PLD), 6 patients received paclitaxel, 2 patients received oral etoposide, and 1 patient received the adriamycin, bleomycin, and vincristine regimen. In the Kaplan-Meier analysis, the PFS was 39.9 months (95% CI, 7.7-72.0). In the first-line setting, a significant difference in terms of PFS was observed between the PLD- and paclitaxel-treated groups (not reached vs. 12.8 months, p = 0.033). The OS was 66.1 months (95% CI, 30.2-102.0). The ORR of the 16 patients was 43.8%, and their DCR was 81.3%. No grade 3 or 4 toxicity was observed. This retrospective study showed that PLD seems better than paclitaxel in terms of PFS and response rates and it has shown to have a good safety profile in KS patients.

Effect of High Fructose Corn Sirup on Pancreatic Ductal Adenocarcinoma Induced by Dimethyl Benzantracene (DMBA) in Rats.

Increased risk of pancreatic cancer may be associated with consumption of sugar containing foods. The aim of this study was to evaluate the effect of peach nectar containing high fructose corn sirup (HFCS) consumption in a pancreatic carcinogenesis rat model induced by 7,12-Dimethyl benzanthracene (DMBA). Fifty-day-old male Sprague Dawley rats were fed with peach nectar containing HFCS + chow, peach nectar containing sucrose + chow and only chow. After 8 mo, feeding period, each group was divided into two subgroups, in which the rats were implanted with DMBA and no DMBA (sham). Histologic specimens were evaluated according to the routine tissue processing protocol. The animals with ad libitum access to pn-HFCS, pn-sucrose and chow (only) showed significant differences in chow consumption and glucose level. Necropsy and histopathologic findings showed tumor formation in the entire group treated with DMBA. Excluding one rat in chow group, which was classified as poorly differentiated type, the others were classified as moderately differentiated pancreatic ductal adenocarcinoma (PDAC). This study demonstrated that daily intake of HFCS did not increase body weight and there was no effect of peach nectar consumption on the development of PDAC induced by DMBA in rats.

The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patients: protocol MF07-01Q.

BACKGROUND/OBJECTIVE: Since more solid evidence has emerged supporting the effectiveness of loco-regional treatment (LRT), clinicians consider LRT a treatment option for selected de novo stage IV breast cancer (BC) patients. This is the first report on long-term quality of life (QoL) in a cohort of patients who were randomized to receive either LRT and then systemic treatment (ST) or ST alone in the protocol MF07-01. We aimed to evaluate QoL in patients living at least 3 years since randomization using scores from the SF-12 health survey. METHODS: SF-12 (V2) forms were completed during visits of patients who were living 36 months after the randomization. We first calculated PCS-12 (Physical Health Composite Scale) and MCS-12 (Mental Health Composite Scale) scores from de novo stage IV BC patients and compared them with the scores of patients diagnosed with stage I-III BC who lived more than 3 years. Further, PCS-12 and MCS-12 scores were compared between the LRT and ST groups with de novo stage IV BC. Additionally, general health, physical functioning, role functioning, bodily pain, vitality, mental health, and social functioning were evaluated and compared between the groups. Considering age-related changes in QoL, we also compared PCS-12 and MCS-12 scores of patients below or above 55 and 65 years of age. Responses to four additional questions (compare your physical health, mental health, daily activities, and energy currently vs. at diagnosis of BC) were recorded, considering cultural differences. RESULTS: There were 81 patients in this analysis; 68% of patients (n = 55) had LRT, and 32% (n = 26) received ST. General health was good or very good in 62% (n = 34) in the LRT group and 66% (n = 17) in the ST-only group (p = 0.63). Mean PCS-12 score was 40.8 + 1.6, and mean MCS-12 score was 43.4 + 2.0 (p = 0.34 and p = 0.54, respectively). PCS-12 and MCS-12 score difference was lower than that of the general Turkish population (PCS-12 = 49.3 + 12.8 and MCS-12 = 46.8 + 13.0) and stage I-III BC patients (PCS-12 = 51.1 ± 0.5, MCS-12 = 45.7 ± 0.6). PCS-12 and MCS-12 scores were similar between the LRT and ST-only groups in patients younger and older than 55 and 65, but QoL scores were much better in stage I-III BC patients younger than 65 when compared to the scores of those with de novo stage IV BC. Although treatment with or without LRT did not affect physical health, mental health, daily activities, and energy at 3 years vs. at diagnosis of BC in de novo stage IV BC patients (p > 0.05), these variables were significantly better in stage I-III BC patients (p < 0.001). CONCLUSION: The current MF07-01Q study demonstrates that patient who had LRT has similar physical and mental health outcomes compared to ST only in a cohort of patients who lived longer than 3 years. Trial registration This study is registered on clinicaltrials.gov with identifier number NCT00557986.

The Ki-67 proliferation index predicts recurrence-free survival in patients with dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma that originates from the dermis or subcutaneous tissue in the skin. While its prognosis is generally favorable, disease recurrence is relatively frequent. Because morbidity after repeated surgery may be significant, an optimized prediction of recurrence-free survival (RFS) has the potential to improve current management strategies. The purpose of this study was to investigate the prognostic value of the Ki-67 proliferation index with respect to RFS in patients with DFSP. We retrospectively analyzed data from 45 patients with DFSP. We calculated the Ki-67 proliferation index as the percentage of immunostained nuclei among the total number of tumor cell nuclei regardless of the intensity of immunostaining. We constructed univariate and multivariate Cox proportional hazards regression models to identify predictors of RFS. Among the 45 patients included in the study, 8 developed local recurrences and 2 had lung metastases (median follow-up: 95.0 months; range: 5.2-412.4 months). The RFS rates at 60, 120, and 240 months of follow-up were 83.8%, 76.2%, and 65.3%, respectively. The median Ki-67 proliferation index was 14%. Notably, we identified the Ki-67 proliferation index as the only independent predictor for RFS in multivariate Cox proportional hazards regression analysis (hazard ratio = 1.106, 95% confidence interval = 1.019-1.200, p = 0.016). In summary, our results highlight the potential usefulness of the Ki-67 proliferation index for facilitating the identification of patients with DFSP at higher risk of developing disease recurrences.

Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study.

BACKGROUND: Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown. METHODS: A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL. RESULTS: Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6th month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42-0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39-0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms. CONCLUSIONS: Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).