The prognostic factors in patients with advanced hepatocellular carcinoma: impact of treatment sequencing.

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

PNI as a Potential Add-On Biomarker to Improve the IMDC Intermediate Prognostic Score.

INTRODUCTION: This study aimed to assess the role of the adjusted PNI-IMDC risk scoring system in stratifying the intermediate group of metastatic RCC patients who received TKIS in the first-line setting. METHODS: A total of 185 patients were included. The adjusted PNI and IMDC model was used to divide the intermediate group into two groups: intermediate PNI-high and intermediate PNI-low groups. The statistical data were analyzed using Kaplan-Meier and Cox regression analysis. RESULTS: The results showed that the adjusted PNI-IMDC risk score, classic IMDC, and PNI had similar prognostic values. Adjusted PNI-IMDC risk score might be used for a more homogeneous differentiation of the classic intermediate group. On the other hand, multivariate analysis revealed that the presence of nephrectomy, adjusted favorable/intermediate (PNI-high) group, ECOG performance score, and presence of bone metastasis were independent predictors of OS. CONCLUSIONS: Pre-treatment PNI, as a valuable and potential add-on biomarker to the adjusted PNI-IMDC classification model, can be helpful for establishing an improved prognostic model for intermediate group mRCC patients treated with first-line TKISs. Further validation studies are needed to clarify these findings.

Relationship between prognostic nutritional index and neutrophil lymphocyte ratio with overall survival in patients with metastatic colorectal cancer receiving regorafenib.

Aim: In this study, we aimed to analyze the effect of prognostic nutritional index and neutrophile lymphocyte ratio on the overall survival (OS) in patients treated with regorafenib. Materials and Methods: Metastatic colorectal cancer (CRC) patients who treated with regorafenib between 2016 and 2020 in a single center were evaluated retrospectively. ROC analysis was used for neutrophile lymphocyte ratio (NLR's) and prognostic nutritional index (PNI's) optimum cut-off value. The relationship between OS with PNI and NLR was investigated. Results: Fifty-two patient's data were analyzed. The median age was 57 years, 22 (41.5%) of the patients were female. The optimal cut-off value of PNI for OS was 45.7 according to ROC curve analysis. The median NLR value was accepted as 2.7. Median OS was 8.3 months. Patients who have high PNI value than 45.7 had longer OS (12.09 months vs. 6.31 months hazard ratio [HR]: 0.37 95% confidence interval [CI]: 0.19-0.73 P = 0.003) and there was a tendency for longer OS with low NLR value then median (12.05 months vs. 6.14 months HR: 0.54 95% CI: 0.29-1.23 P = 0.057). Primary tumor resected patients had longer OS than nonresected patients (12.05 months vs. 6.30 months HR: 0.34 95% CI: 0.17-0.66 P = 0.001). In multivariate analysis, high PNI value more than 45.7 (HR: 0.40 95% CI: 0.18-0.88 P = 0.02) and resection of the primary tumor (HR: 0.40 95% CI: 0.21-0.80 P = 0.01) were the only independent factors for longer OS. Conclusion: Metastatic CRC patients with high pretreatment PNI and primary tumor resected are more likely to have longer OS with regorafenib. PNI is more reliable index than NLR to predict OS in metastatic CRC patients treated with regorafenib.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Prognostic nutritional index and its dynamics after curative treatment are independent prognostic factors on survival in non-metastatic nasopharyngeal carcinoma.

PURPOSE: We aimed to identify the prognostic and predictive values of post-treatment prognostic nutritional index (PNI) and PNI dynamics in nasopharyngeal cancer patients (NPC) in this study. METHODS: One hundred seven non-metastatic NPC patients were included. PNI was calculated by using the following formula: [10 × serum albumin value (gr/dL)] + [0.005 × total lymphocyte count (per mm3)]. ROC analysis was used for determining prognostic PNI values and univariate and multivariate statistical analyses for prognostic characterization of PNI. RESULTS: The statistically significant cut-off values for pre- and post-treatment PNI were 50.65 and 44.75, respectively. Of the pre-treatment PNI analysis, PNI ≤ 50.65 group had shorter loco-regional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Furthermore, for post-treatment PNI analysis, PNI ≤ 44.75 group had shorter LRRFS and OS. In univariate analysis, only pre-treatment PNI was associated with LRRFS and DMFS, while pre- and post-treatment PNI were both associated with OS. In multivariate analysis, both PNI were independent prognostic markers for OS. In the combined analysis, pre- and post-treatment PNI, differences between the groups were statistically significant, and the PNI dynamics was an independent prognostic indicator for OS. CONCLUSION: PNI is a useful, independent prognostic marker for non-metastatic NPC patients. It is used for either pre- or post-treatment patients. Furthermore, changes in pre-treatment PNI value after curative treatment is a significant indicator for OS.

Prognostic Factors for Survival in Transverse Colon Cancers.

BACKGROUND: Transverse colon cancer (TCC) is a rare condition that accounts for 10% of all colon cancers. TCC was accepted more likely right-sided colon cancers. We aimed to investigate whether TCC differs from other colon tumors by using clinical, pathological, and molecular prognostic factors known to be important in colon cancer and if it differs in its own anatomical structure. PATIENTS AND METHODS: We evaluated local and locally advanced TCC patients between 2007 and 2020 years for demographics data, symptoms, treatment status, and histopathological and molecular features. RESULTS: Overall, 107 TCC patients were included in this study. According to the molecular data analysis of 44, 35, and 23 patients for MSI, RAS, and BRAF status, respectively, 7 (15.9%) were MSI-H, 13 (37.1%) were RAS mutant, and 11 (47.8%) had BRAF V600E mutation. The median follow-up time was 31.5 months. Median disease-free survival (DFS) was 5.19 months, and median OS was 88.3 months for the whole study population. The tumor stage was the most significant prognostic factor for DFS and OS. Although BRAF mutation was not a significant marker for DFS, it was an independent prognostic marker for OS (HR 3.90 95% CI 1.42-10.7). There were no statistically significant differences between proximal two-thirds and distal one-third tumor location. CONCLUSION: TCC has molecular features and prognostic factors more likely RCC and no differences between proximal and distal sub-parts. BRAF V600E mutation status is an independent predictor of survival even in the early stages of TCC.

The relationship between FDG PET/CT-defined metabolic parameters and the histopathological subtype of oesophageal carcinomas.

PURPOSE: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) combined with computed tomography (CT) scan is accepted as a standard tool in the staging of oesophageal cancer (OC). Histological subtype of tumour is known to be a major determinant of prognosis and metabolic behaviour. In this study, we aimed to evaluate the effect of histological subtypes of OC on standard uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) obtained by PET/CT, and also to compare this effect with prognosis. MATERIAL AND METHODS: Images and clinical course data of 57 patients who were diagnosed with EC and treated in our hospital between 2009 and 2016 were evaluated in a retrospective manner. PET/CT images were re-analysed in terms of metabolic parameters, and observations were compared with histological subtypes. RESULTS: No significant difference was observed between histological subtypes with SUVmax, overall survival (OS), or progression-free survival (PFS). Thus, MTV was observed to be related with histological subtype; MTV values of adenocancer patients were significantly higher than those of squamous cell cancer patients. CONCLUSIONS: Metabolic tumour volume was related with histological subtype of OC, but clinical staging, TLG, and SUVmax values were not related with histological subtype, which may suggest the use of MTV as a routine parameter for OC and inclusion of MTV observations in prognostic scoring.

Contrast nephropathy in cancer patients receiving anti-VEGF therapy: a prospective study.

OBJECTIVES: Contrast nephropathy risk has been increasing in cancer patients. Nephrotoxic side effects of anti-vascular endothelial growth factor/receptor (anti-VEGF/R) drugs used in oncologic treatment are also prominent. The purpose of this study was to identify the possible association among anti-VEGF/R drugs use and development of the contrast-induced nephropathy (CIN) in patients with cancers. METHODS: A total of 92 patients were included in this prospective cross-sectional study. Patients whose glomerular filtration rate (GFR) of < 50 ml/min, hemoglobin of < 10 g/dl, and eastern cooperative oncology group (ECOG) score of ≥ 2 and had received nephrotoxic drugs were not included in the study. Blood samples were collected baseline at pre computed tomography (CT) and day 2, day 3 and day 7 later CT imaging. CIN was defined as either an increased serum creatinine value of 0.5 mg/dl or increased 25% to baseline. CIN frequency between groups receivingand not receiving anti-VEGF/R was compared using the chi-squared test. CIN frequency between bevacizumab and other anti-VEGF/R was also analyzed. RESULTS: There were 39 patients in the anti-VEGF/R (+) group and 53 patients in the anti-VEGF/R (-) group. Eleven patients (28%) in the anti-VEGF/R (+) group and 3 patients (5.6%) in the anti-VEGF/R (-) group had CIN (p = 0.006). In the anti-VEGF/R (+) group, 23 patients received bevacizumab (combined with FOLFOX/FOLFIRI), while 16 patients received other anti-VEGF/R (sunitinib, axitinib, regorafenib, aflibercept) effective treatments. CIN ratio in patients who received bevacizumab or other anti-VEGFR therapy was similar (p = 0 = 50). Of the patients, one patient had acute kidney injury leading to death. CONCLUSION: CIN was significantly more frequent in cancer patients who receiving anti-VEGF/R drugs than those not receiving anti-VEGF/R drugs.

Is the Charlson Comorbidity Index a Prognostic Indicator for Toxicity and Mortality in Elderly Patients with Locally Advanced Rectal Cancer?

BACKGROUND: Aging is significantly related to multiple comorbidities. Even with a good performance score, some elderly patients may have poor survival outcomes. We aimed to evaluate the prognostic value of the Charlson comorbidity index (CCI) for mortality and toxicity in elderly patients with locally advanced rectal cancer (LARC). METHODS: Seventy-two elderly patients with LARC who were treated with neoadjuvant chemoradiotherapy (CRT) were included. Based on their CCI score, severity of the comorbidity was categorized into 2 groups: CCI<7 and CCI≥7. RESULTS: The overall survival (OS) at 5 years was 54.4 percent in patients treated with neoadjuvant CRT. Median OS was not reached for all patients as well as patients with CCI score <7, but median OS was 25 (95% CI 1.0-62.1) months in patients with CCI≥7 (P=0.002). The OS at 2 years was 79.1 percent in the patients with CCI <7 and 50.0 percent in the patients with CCI score ≥7 (P=0.002). Moreover, there was a trend toward, patients with higher CCI score who had more treatment related to grade 3 or 4 toxicity compared to those with CCI score <7 (33.3% vs 13.3%, respectively, P=0.09). Multivariable analysis indicated that the CCI score ≥7, presence of down-staging after therapy and clinical stage (III) independently predict mortality (HR 6.14, 95%CI 2.45-15.35, P<0.001) in patients with LARC. CONCLUSION: Although CCI score was not significantly associated with both toxicity and disease-free survival (DFS), we suggest that baseline CCI score might be a valuable prognostic indicator for physicians to evaluate elderly patiens with LARC for optimal treatment.

Changes in skeletal muscle area and lean body mass during pazopanib vs sunitinib therapy for metastatic renal cancer.

PURPOSE: To evaluate whether sunitinib and pazopanib treatments are associated with change in skeletal muscle area (SMA) and total lean body mass (LBM) as well as to compare their efficacies and safety profiles in patients with metastatic renal cell cancer (mRCC). METHODS: Thirty-six patients treated with a tyrosine kinase inhibitor were included. Eighteen of them received sunitinib and the rest/remaining received pazopanib in the first line of mRCC treatment. Baseline and follow-up computed tomography studies of the patients were performed to measure cross-sectional areas (cm2) of muscle tissues. RESULTS: About 69% of patients were male and median age was 60 (49-68) years. Median time interval between two CT imagings was 6.1 (3.1-7.7) months and it was similar between the two groups (for sunitinib, 4.9 (2.5-6.9) months vs for pazopanib, 7.3 (3.2-9.5) months, p = 0.16, respectively). Disease control rate was 77.7% in all patients. Of these, 66.6% in sunitinib group was consisted of four partial responses and eight stable diseases. In addition, 88.8% in pazopanib group was consisted of three partial responses and 13 stable diseases. A significant decrease in SMA and LBM was observed after sunitinib therapy, whereas SMA and LBM values of pazopanib group did not change significantly (p = 0.02 and p = 0.70, respectively). No significant differences were observed between patients with sunitinib, and pazopanib group median PFS [11.9 (95% CI 6.1-17.6) vs 8.1 months (95% CI 7.2-9.1), respectively; p = 0.28] and median OS [28.6 (95% CI 24.3-32.9) vs 25.5 months (95% CI 18.9-52.7), respectively; p = 0.42]. Dose-limiting toxicities were significantly more frequent in sunitinib group than in pazopanib group (66.7% vs 22.2%, p = 0.02, respectively). CONCLUSIONS: Loss of SMA and LBM with sunitinib was more substantial than with pazopanib. Treatment efficacies of both drugs were similar, but dose-limiting toxicity was more frequent in sunitinib group. Loss of SMA had no significant association with prognosis. Further studies are needed to clarify the possible association between SMA and prognosis in mRCC patients who receive sunitinib or pazopanib.

Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?

PURPOSE: To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting. MATERIALS AND METHODS: The data of 104 patients diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months. RESULTS: A total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16-0.54, p < 0.001). Median OS was 12.0 months (95% CI 8.1-15.9) in rechallenge versus 6.6 months (95% CI 6.0-7.3) in regorafenib group (p < 0.001). Progression-free survival in the rechallenge group showed a higher median value of 9.16 months (95% CI 7.15-11.18) versus with that recorded in the regorafenib group of 3.41 months (95% CI 3.01-3.82), in favor of rechallenge chemotherapy. The most common adverse events of regorafenib was liver function test abnormality and hand-foot syndrome. Although grade 3 or 4 adverse events were similar, non-hematologic toxicities were more common than those of rechallenge. CONCLUSIONS: Rechallenge is still a valuable option against regorafenib in patients who achieved disease control in one of the first two lines of therapy. Even though mCRC patients treated with regorafenib benefited clinically from this treatment, we revealed that chemotherapy rechallenge compared to regorafenib was more effective in the third-line treatment for mCRC patients.

Durable complete response with a short course of streptozotocin plus doxorubicin combination in malignant metastatic insulinoma.

Due to the cytotoxic effects of old chemotherapy regimens used in the islet cell tumors, capecitabine plus temozolomide combination has now become the first choice in the treatment of malignant insulinoma (MIoma). We present this case to emphasize and remind that a durable complete response in advanced stage MIoma may be achieved with a short course of streptozotocin plus doxorubicin combination.

Renal cell carcinoma presenting with heart metastasis without inferior vena caval and right atrial involvement.

Heart metastasis of renal cell carcinoma (RCC) without vena cava inferior involvement is exceptionally rare. Here, we presented a case of RCC presenting with the right ventricle metastasis without inferior vena caval and right atrial involvement.

Clinical features of the patient with multiple primary tumors: Single center experience.

OBJECTIVE: Multiple primary tumors are the ones that develop in the same patient at the same or different times. They are usually examined under two groups. If the second tumor is diagnosed 6 months after the first tumor is diagnosed, it is named as metachronous tumor. If it is diagnosed in 6 months after the first diagnosis, it is called as synchronous tumor. The malignancy of tumors should be proved histologically. At least 2 cm of solid tissue should be present between two tumors. If they are at localized at the same place, a gap of at least 5 years should be present between them. Metastatic disease should be eliminated. This study aimedto review the clinical, demographic, and pathological features of multiple primary tumors, detect the prevalence, compare the results with literature findings, and evaluate and improve the approach to multiple primary tumors. METHODS: A total of 170 patients diagnosed with multiple primary tumors were included in this study. Patient data were obtained from pathology and medical reports of the patients. RESULTS: Most of the multiple primary tumors were metachronous. The number of male patients was more than that of female patients. The median time between double tumors was 3 monthsforsynchronous tumorsand 26 months for metachronous tumors. Synchronous tumors with the highest prevalence of comorbidity were lung-larynx and lung-colon, whereas metachronous tumors with the highest prevalence of comorbidity were lung-bladder, lung-larynx, breast-endometrium, and breast-colon. The history of smoking and alcohol was found to be higher in male patients andsynchronous tumors. CONCLUSION: The detection of the first tumor in the metastatic stage and an accompanying synchronous secondary tumor was found to be a poor prognostic factor. The treatment of the first tumor, smoking, squamous cell histology, and male gender were among the other factors negatively affecting survival, although they were not statistically significant.

A rare coexistence--Chronic lymphocytic leukemia and Kaposi sarcoma: Case report and review of the literature.

Chronic lymphocytic leukemia (CLL) is the most common leukemia worldwide. Skin lesions associated with CLL mostly develop on the bases of infectious or a hemorrhagic origin with an estimated incidence of 25% of all the cases. Kaposi sarcoma (KS)-associated with human herpes virus-8 infection is a spindle-cell, malignant, low-grade tumor originating from vascular and lymphatic endothelium. KS mostly presents with skin lesions as the initial presentation. The relation between these two pathologies has not yet been clarified up to date. Herein, we report a case of KS along with CLL to illustrate the possible relation between these two pathologies.