Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

Prognostic significance of mucinous histology in left­sided metastatic colorectal cancers with wild­type RAS and evaluation of backbone chemotherapy regimens.

Mucinous colorectal adenocarcinoma (MCAC) is a distinct subtype of colorectal carcinoma (CRC). The prognostic and predictive significance of mucinous histology remains controversial. It was aimed to investigate the prognostic and/or predictive role of mucinous histology in left-sided metastatic CRC (mCRC) with wild-type RAS. This is a retrospective multicenter study of mCRC treated with first line anti-EGFR combined 5-fluorouracil based chemotherapy (CT). Patients were stratified according to presence (>50% extracellular mucin) or absence of mucinous histology. Survival analyses were performed firstly regardless of treatment options and then performed as separating according to CT regimens. Additional analyses were performed for MCAC patients considering backbone CT regimens. A total of 125 patients were included, consisting of 40 (32.0%) patients with MCAC and 85 (68.0%) patients with non-MCAC. Median follow-up time was 19.7 months. Median progression-free survival (PFS) was 10.7 months in all patients, and PFS was lower in MCAC than non-MCAC (9.9 vs. 12.0 months, respectively, P=0.005). Median overall survival (OS) was 25.7 months in all patients. OS was lower in MCAC than non-MCAC (22.8 vs. 29.7 months, respectively, P=0.005). When considering backbone CT regimens, in multivariate analyses, mucinous histology was an independent prognostic factor for OS in both for mFOLFOX6 (HR: 1.92, P=0.04) and FOLFIRI (HR: 2.04, P=0.04) groups and was associated with poor PFS in only mFOLFOX6 (HR: 3.86, P<0.001) group. When outcomes were analyzed for the MCAC group, median OS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 22.47 and 14.22 months, respectively (P=0.41). Median PFS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 10.15 and 8.11 months, respectively (P=0.73). The study revealed poor prognosis of mucinous histology, both in whole study population and in backbone CT groups. Moreover, lower PFS of MCAC patients was revealed in only mFOLFOX6 group and this finding may be a valuable issue for the future research. However, considering all analyses, the present results did not indicate a special benefit of any backbone CT regimen for MCAC patients.

Prognostic value of Gustave Roussy immune score in operable pancreatic adenocarcinoma.

Background: The Gustave Roussy immune score (GRIm score) is a laboratory index developed to predict survival in nonsmall cell lung cancer patients undergoing immunotherapy and has shown that the pretreatment value is an independent prognostic factor for survival. In this study, we aimed to determine prognostic significance of GRIm score for pancreatic adenocarcinoma that have not been determined in the literature for pancreatic cancer before. The reason for choosing this scoring is to show that the immune scoring system works as a prognostic marker in pancreatic cancer known as immune-desert tumor via immune properties of microenvironment. Methods: Medical records of patients with histologically confirmed pancreatic ductal adenocarcinoma, who were treated and followed up between December 2007 and July 2019 at our clinic, were reviewed retrospectively. GRIm scores of each patient were calculated at the time of diagnosis. Survival analysis were performed according to risk groups. Results: A total of 138 patients were included in the study. While 111 (80.4%) patients were in the low-risk group; 27 (19.6%) were in high-risk group according to GRIm score. Median OS was 36.9 months (95% Confidence interval (CI): 25.42-48.56) in lower GRIm scores, and it was 11.1 months (95% CI: 6.83-15.44) in higher GRIm scores (P = 0.002). One-two-three-year OS rates were 85% versus 47%, 64% versus 39%, 53% versus 27% for low versus high GRIm scores, respectively. The multivariate analysis revealed that high GRIm score was an independent poor prognostic factor. Conclusion: GRIm can be used as a noninvasive, easily applicable, practical prognostic factor in pancreatic cancer patients.

Prognostic significance of 18F-FDG PET/CT indices in metastatic renal cell cancer and evaluation of revised IMDC risk model by including 18F-FDG PET-CT parameters.

BACKGROUND: Prognostic markers in metastatic renal cell cancer (mRCC) are still insufficient. Any prognostic model objectively determines disease burden. PURPOSE: To investigate the relationship between 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and outcomes in mRCC, and to define a revised International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model for the intermediate-risk group. MATERIAL AND METHODS: A retrospective study of mRCC was conducted. To investigate the prognostic significance of 18F-FDG PET/CT parameters, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were determined in pre-treatment images. Cutoff values were defined by ROC curve analyses and their association with outcomes was analyzed. Additionally, a TLG-adjusted IMDC model was created by stratifying intermediate-risk group patients according to TLG levels. RESULTS: The study included 52 patients. The disease control rate (DCR) was 61.5% and median overall survival (OS) was 18 months (95% confidence interval=9.2-25.8). In the univariate analyses, IMDC score, MTV, and TLG were prognostic factors for Disease Control Rate (DCR), and Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS), IMDC score, lactate dehydrogenase (LDH), treatment option, MTV, and TLG were prognostic factors for OS (P < 0.05 each). In the multivariate analyses, MTV was an independent prognostic factor for DCR, and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. According to the revised-IMDC model, the intermediate-favorable group showed longer OS than the intermediate-unfavorable group. CONCLUSION: Pretreatment MTV was independent prognostic factor for DCR and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. Revised-IMDC model could identify patients with a worse prognosis among the IMDC intermediate-risk group.

Age-adjusted Charlson Comorbidity Index is a valuable prognostic tool in operable soft tissue sarcoma of trunk and extremities.

BACKGROUND: Advanced age and presence of comorbidities affect prognosis and treatment decisions in patients with soft tissue sarcoma (STS). However, coeffect of age and comorbidities is still unknown. We aimed to investigate prognostic value of age-adjusted Charlson Comorbidity Index (ACCI) in trunk and extremity STS operated with curative intent. HYPOTHESIS: Preoperative ACCI might predict survival outcomes independently in patients with STS of trunk and extremities. PATIENTS AND METHODS: The study included 151 patients and ACCI was calculated for each patient. We categorized the patients into two groups according to median ACCI. We retrospectively collected data about clinicopathologic and treatment-related factors, and evaluated potential prognostic factors for disease-free survival (DFS) and overall survival (OS) using univariate and multivariate analyses. RESULTS: Median age was 50 (18-86) years. There were 89 male and 62 female patients. Lower extremities were the most common tumor sites (73.5%). Most of the patients had high grade tumors (84.1%) and stage 3 disease (66.9%). Radiotherapy and chemotherapy were carried out in 106 and 58 patients, respectively. Overall prevalence of comorbidity was 29.1%. Median ACCI was 3 (2-9). Older age (p<0.001), worse performance status (p<0.001), larger tumor size (p=0.03), higher grade tumors (p=0.03) and advanced stage (p=0.04) were associated with higher ACCI (≥3). Median follow-up time was 32 months, 50.3% of patients had disease recurrence, and 35.8% died. Median DFS (p=0.001) and OS (p=0.001) of patients with low ACCI (<3) were significantly longer than patients with high ACCI. Multivariate analysis determined ACCI as an independent prognostic indicator for both DFS (HR 1.72, p=0.02) and OS (HR 2.02, p=0.04). DISCUSSION: ACCI is a valuable prognostic tool to be used in the preoperative setting of patients with STS. Higher ACCI was found to be independently associated with worse survival outcomes. For each patient with STS, evaluating comorbidities and combining them with age appears to be a critical step in modifying therapy options. LEVEL OF EVIDENCE: IV, retrospective observational study.

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).

Role of baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters in predicting survival outcomes of metastatic castration-resistant prostate cancer patients receiving first-line treatment.

OBJECTIVE: We aimed to evaluate whether baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters could be used as predictive biomarkers for survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line treatment. MATERIALS AND METHODS: This retrospective study included 54 mCRPC patients, who underwent baseline 68Ga-PSMA PET/CT imaging within 1 month before starting first-line treatment. Pre-treatment prostate-specific antigen (PSA) levels and treatments were recorded. SUVmax, SUVmean, whole-body PSMA-derived tumor volume (wbPSMA-TV), and whole-body total lesion PSMA (wbTL-PSMA) were calculated for all patients. PSA response was defined as a decline of ≥ 50% from pre-treatment value at 12 weeks. Overall survival (OS) was measured from the start of the first-line treatment for mCRPC. RESULTS: Docetaxel and abiraterone/enzalutamide were administered to 32 and 22 patients in the first-line setting, respectively. wbPSMA-TV (rho = 0.582, p = 0.004) and wbTL-PSMA (rho = 0.564, p = 0.007) showed moderate positive correlations with PSA levels. Older age (p = 0.02), higher wbPSMA-TV (p = 0.007), higher PSA (p = 0.01), higher number of bone metastases (p = 0.02), and lack of PSA response (p = 0.03) were significantly associated with an increased risk of mortality. Multivariate analysis determined wbPSMA-TV (HR: 1.003, 95% CI 1.001-1.004, p = 0.001) and PSA response (HR: 2.241, 95% CI 1.189-4.222, p = 0.01) as independent predictors of OS. CONCLUSION: The wbPSMA-TV may be a useful tool to reflect tumor burden and predict survival outcomes in patients with mCRPC.

Real-world assessment of quality-of-life in patients with breast cancer treated with adjuvant endocrine therapy.

Objective: The aim of this study was to investigate quality-of-life (QoL) in breast cancer (BC) patients treated with adjuvant endocrine therapy (AET). Methods: We designed a cross-sectional study of 233 BC patients treated with AET and used the Functional Assessment of Cancer Therapy - Breast questionnaire. Results: No significant difference was observed between endocrine agents. Duration of AET did not affect QoL. In the entire cohort, multivariate analysis determined age (p = 0.034) and switching treatment from tamoxifen to aromatase inhibitors (p = 0.049) as significant positive coefficients of QoL, while comorbidity (p = 0.072) tended to be associated with lower scores. Education level (p = 0.001) and chemotherapy (p = 0.04) were significant predictors of QoL in the tamoxifen group, while comorbidity (p = 0.04), surgery type (p = 0.02), radiotherapy (p = 0.006) and stage (p = 0.009) had a significant impact on QoL in aromatase inhibitors group. Conclusion: Evaluating the well-being of BC patients by QoL questionnaires is of great importance to identify particular subgroups that may require supportive care.

Breast cancer (BC) remains the most common cancer among women worldwide. Hormone receptor-positive (estrogen receptor- and/or progesterone receptor-positive) BC represents 70% of all cases. Advances in the treatment of disease lead to improved patient survival. As a result, quality-of-life (QoL) becomes a major concern in clinical practice. This study aimed to assess the impact of socio-demographic, clinical and treatment-related factors on QoL among patients with BC treated with adjuvant endocrine therapy. We used the Functional Assessment of Cancer Therapy ­ Breast questionnaire to evaluate QoL. In the entire cohort, multivariate analysis determined age and switching treatment from tamoxifen to aromatase inhibitors to be significant positive coefficients of QoL, while comorbidity tended to be associated with lower scores. Education level and chemotherapy were significant determinants of QoL in the tamoxifen group, while comorbidity, surgery type, radiotherapy and disease stage had a significant impact on QoL in the aromatase inhibitor group. These findings can be utilized to identify certain subgroups that may need greater supportive care.

Predictive value of 18F-FDG PET/CT indices on extensive residual cancer burden in breast cancer patients treated with neoadjuvant chemotherapy.

AIM: We investigated the correlation between 18F-FDG PET/CT indices and pathological response in breast cancer treated with neoadjuvant chemotherapy (NACT) which was scored with Residual Cancer Burden (RCB) system after surgery. Our aim is to detect extensive residual cancer burden earlier by using PET/CT indices. METHODS: Characteristics of patients were retrieved retrospectively. Baseline maximum Standart Uptake Value (SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) indices and reduction rate (RR) between baseline and interim evaluation were calculated with FDG PET/CT scan. All patients were evaluated according to RCB scores after surgery. Pathological responses and PET/CT measurement results were analyzed with demographic and clinical parameters. RESULTS: A total of 95 patients were included in the study. According to pathological responses, the distribution of RCB -0, -1, -2, -3 were 13 (13.7%), 11 (11.6%), 30 (31.6%), 41 (43.2%), respectively. Disease-free survival was significantly lower in the RCB3 group compared to the pathological responder group (p = 0.01). According to multivariate analysis, RR of SUVmax was determined as an independent variable predicting extensive residual cancer burden with an optimal cut-off value of 86% (p < 0.05). CONCLUSIONS: We determined RR of SUVmax as an independent factor for predicting extensive residual tumor burden. We believe that RR of SUVmax is sufficient to predict pathological response in daily practice. In addition, MTV and TLG measurements do not contribute additionally to SUVmax alone and can cause unnecessary labor loss.

Impact of Skeletal Muscle Measurements by Chest Computed Tomography on Survival and Postoperative Complications in Patients with Soft Tissue Sarcoma.

This study aims to evaluate whether sarcopenia, measured by chest computed tomography (CT), affects survival outcomes and postoperative complications in soft tissue sarcoma (STS) patients undergoing surgery. In this retrospective study, CT scans of 79 patients were reviewed to measure pectoralis and T12 vertebra muscle area. Both were then adjusted for height (cm2/m2) as pectoralis muscle index (PMI) and T12 vertebra muscle index (TMI). Analyses were performed by dichotomizing muscle indices at gender-specific 50th percentile; PMI and TMI < 50th percentile were defined as low, and ≥50th percentile as high. Overall postsurgical complication rate (PCR) was 16%. Median length of hospital stay (LOHS) was 10 days (3-90). PMI and TMI were significantly lower in women (p = 0.02, p = 0.04). Median body mass index was significantly higher in high PMI and TMI groups (p = 0.01 for both). PCR and LOHS were similar between low and high PMI and TMI groups. Median follow-up was 29 months, 37 patients had recurrence and 23 died. No significant difference was noted between low and high PMI and TMI groups, in terms of disease-free or overall survival. PMI and TMI as measured by chest CT had no impact on survival outcomes or postoperative complications in localized STS.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma differs from other solid tumors with its unique immunosuppressive microenvironment and non-immunogenic feature. There are not many studies in the literature investigating the effect of these features on prognosis. Aims: To investigate the prognostic value of tissue-resident memory T cells, tumor microenvironment features, and tumor-associated immune cells in resected pancreatic ductal adenocarcinomas. Study Design: Retrospective cross-sectional study. Methods: Of 138 patients diagnosed with pancreatic ductal adenocarcinoma between 2011 and 2018, 81 were included in the study. Specimens from operated patients were reassessed separately as peritumoral and intratumoral areas for tissue resident memory cells and tumor microenvironmental elements (tumor infiltrating lymphocytes, tumor stroma, CD204+ macrophages, PDL1+ immune cells). Disease-free survival and overall survival were defined from the date of operation to the date of recurrence and the date of first diagnosis to the date of death, respectively. If the patient was alive, the last visit date was taken into account. Results: The median age at diagnosis was 63 (range: 40-78). The median follow-up period was 18.9 months (range: 1.4-80.4 months). Median overall survival was 23.7 months (1.4-80.4 months) and median disease-free survival was 10.8 months (1.4-74.4 months). Patients with higher intra-tumoral tissue-resident memory cell counts had a longer survival trend than those having lower values (25.6 months vs. 18 months, respectively, P = .84). According to microenvironmental evaluations, lower stromal score (defined as stroma having less desmoplasia and rich in cells) and presence of peritumoral Crohn's-like inflammatory response were associated with higher survival (29.2 months vs. 19.7 months for low vs. high stromal scores, respectively, P = .16 and 30.2 months vs. 18.1 months for the presence of Crohn's-like inflammatory response P = .13). Decreased survival was observed in tumors with increased CD204+ tumor-associated macrophages which were immunosuppressive elements of the microenvironment (12 months vs. 26.3 months for intra-tumoral assessment, P = .29). Conclusion: Tissue-resident memory T cells and other microenvironmental features may be prognostic in resectable pancreatic ductal adenocarcinomas. Further studies with larger cohorts are needed for validation.

A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study.

BACKGROUND: Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated. METHODS: The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year. RESULTS: Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively. CONCLUSIONS: Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease (trial registration: clinicaltrials.gov the identifier: NCT01748773, December 13, 2012, https://clinicaltrials.gov/ct2/show/NCT01748773).

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

PURPOSE: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). METHODS: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. RESULTS: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). CONCLUSION: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Differences in PET/CT standardized uptake values involvement and survival compared to histologic subtypes of lung adenocarcinoma.

PURPOSE: Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes. METHODS: We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes. RESULTS: The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p = 0.000). There was no significant difference in OS between histologic subtypes (p = 0.66), but PFS was significantly different between the groups (p = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes. CONCLUSION: Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

PURPOSE: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. METHODS: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. RESULTS: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). CONCLUSION: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

Rechallenge with dabrafenib plus trametinib in anaplastic thyroid cancer: A case report and review of literature.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is a highly aggressive, undifferentiated rare tumor. Median overall survival is usually between 8 and10 months, with a 1-year survival rate of 20%. Conventional anthracycline based chemotherapy regimens demonstrate low response rates with short duration. Novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape of ATC have been investigated. CASE PRESENTATION: We herein report the rechallenge of a 52-year-old ATC patient with BRAF V600E mutation with dabrafenib plus trametinib. She presented with recurrent and progressive disease despite surgery, radiation therapy, 3 different chemotherapy regimens, and combination of dabrafenib-trametinib in different settings. She was rechallenged with dabrafenib-trametinib, and had a good response. CONCLUSION: To our knowledge, this is the first ATC case who responded to dabrafenib-trametinib rechallenge, reported in the literature. We want to emphasize that combination of dabrafenib and trametinib might be a good choice for resistant locoregional and metastatic ATC patients with BRAF V600E mutation, particularly in whom rapid clinical response is urgently needed. Moreover, rechallenge with this combination should be kept in mind in selected cases.

A rare case of gastric cancer with bilateral breast metastasis during pregnancy.

BACKGROUND: Gastric cancer is rare during pregnancy and often diagnosed at a later stage due to overlapping symptoms of pregnancy. Breast metastasis of gastric cancer is another uncommon entity. We present a rare case of breast metastasis of gastric cancer during pregnancy. CASE REPORT: A 26-year-old female was diagnosed with gastric cancer at 14 weeks of gestation and underwent total gastrectomy. She rejected adjuvant chemotherapy and continued pregnancy without any follow-up. Cancer recurred in bilateral breasts at 34th week of gestation mimicking primary inflammatory breast cancer. MANAGEMENT AND OUTCOME: It was difficult to diagnose breast metastasis during pregnancy because of overlapping pregnancy symptoms. Following an unresponsive period to antibiotherapy, a fine needle biopsy on breast was performed and signet cell adenocarcinoma metastasis was determined. We started chemotherapy after delivery. There was a near complete response after first line of chemotherapy. Unfortunately, cancer was relapsed within three months and we started second-line chemotherapy. DISCUSSION: To our knowledge, this is the fourth case reported in medical literature of gastric cancer presented with breast metastasis during pregnancy. We will try to draw attention to diagnosis, treatment and different presentation of gastric cancer during pregnancy with review of the literature.