Advancements in the Management of Synchronous Colorectal Liver Metastases: A Comprehensive Review of Surgical, Systemic, and Local Treatment Modalities.

PURPOSE OF REVIEW: This review addresses the current landscape of colorectal cancer (CRC) with a focus on liver metastases, the third most common cancer globally. It explores recent findings in treatment strategies, emphasizing the dynamic interplay between surgery, systemic chemotherapy, and local therapies for synchronous colorectal liver metastases (CRLMs). RECENT FINDINGS: Highlighting the role of advanced imaging, the review underscores the significance of contrast-enhanced MRI in surgical planning for CRLMs. Surgical resection remains a primary choice for resectable cases, with considerations for oncologic scoring systems and tumor biology. Perioperative systemic chemotherapy plays a pivotal role, especially in conversion therapy for initially unresectable CRLMs. The review also explores various local therapies, including radiofrequency ablation, microwave ablation, stereotactic body radiotherapy, hepatic arterial infusional chemotherapy, selective internal radiation therapy, and transarterial chemoembolization for unresectable cases. A comprehensive approach, integrating surgery, systemic chemotherapy, and local therapies, is crucial for managing synchronous CRLMs. Surgical resection and perioperative chemotherapy are key players, guided by considerations of tumor biology and scoring systems. For unresectable cases, local therapies offer viable alternatives, emphasizing the need for tailored treatments. Multidisciplinary collaboration among medical oncologists, surgeons, and radiologists is essential. Ongoing research will refine treatment approaches, while emerging technologies hold promise for further advancements in managing colorectal liver metastases.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG).

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Exploring the connection between microsatellite instability and inflammatory indicators in cancers.

Aim: This study aimed to investigate the association between microsatellite instability (MSI) status and inflammatory indicators in patients with cancer. Patients & methods: A total of 204 patients with various cancer diagnoses, including 102 with MSI-high (MSI-H) and 102 with microsatellite stable tumors, were enrolled. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP)-to-albumin ratio and systemic immune-inflammation index were evaluated. Results: In microsatellite stable patients, NLR, LMR, PLR and systemic immune-inflammation index were significantly linked to worse survival in univariate analysis, and having a LMR ≤2.6 negatively affected survival in multivariate analysis, although these indicators did not affect the survival of MSI-H patients. Conclusion: The impact of chronic inflammation on survival varies with MSI status. Further research is needed for targeted therapies in different tumors.

Impact of antihistamine use on the survival outcomes of immune checkpoint inhibitors in advanced cancer patients.

Histamine and H1 receptors play a crucial role in the tumor microenvironment. Preclinical data showed that concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) might increase the effect of ICIs. This study aimed to evaluate the impact of antihistamines on the oncological outcomes of ICIs. This retrospective study was conducted in a tertiary cancer center. Advanced cancer patients treated with ICIs were included in this study. A total of 133 patients receiving ICIs in the metastatic setting were included. Melanoma (33.1%) was the most common tumor type. The most common ICI was nivolumab (63.2%). Fifty-five (38.4%) patients received antihistamines concomitantly with ICIs. The most common antihistamine was pheniramine (85.5%). The median progression-free survival (PFS) (8.2 vs. 5.1 months, P  = 0.016) and overall survival (OS) (16.2 vs. 7.7 months, P  = 0.002) were longer in patients receiving antihistamines concomitantly with ICIs. In multivariate analysis, PFS [hazard ratio (HR) = 0.63, 95% CI: 0.40-0.98, P  = 0.042] and OS (HR = 0.49, 95% CI: 0.29-0.81, P  = 0.006) were also better in those patients after adjusting for confounding factors, such as performance status, bone or liver metastasis, and concurrent chemotherapy. This study suggested that antihistamines may enhance the efficacy of ICIs in patients with advanced cancer. If validated in prospective trials, antihistamines and ICIs combinations might be new options to improve oncological outcomes.

Relationship Between ABO Blood Group and Microsatellite Instability in Colorectal Cancer: A Retrospective Single-Center Study.

PURPOSE: Colorectal cancer (CRC) is the second most common cancer in both women and men. Microsatellite instability-high (MSI-H) CRC is a molecular subgroup and has distinct clinical and pathologic features from microsatellite stable (MSS) CRC. Studies have suggested an association between hereditary antigens in ABO blood group system and the risk of developing various cancers but the relationship between blood groups and MSI-H CRC has not been investigated. This study aimed to investigate this relationship and its possible effect on clinicopathological features in patients with CRC. METHODS: This is a retrospective cross-sectional single-center study including pathology-confirmed CRC patients. Demographic and clinicopathological features, blood groups, and microsatellite status were examined among two groups. Microsatellite instability was examined by immunohistochemistry (IHC) in pathology specimen. RESULTS: A total of 144 patients, 72 patients with MSI-H CRC and 72 patients with MSS CRC, were included in the study. Among all patients, median age was 61.7 ± 12.9 (range 27-89) and 57.6% were male. MSI-H and MSS groups were similar in terms of age, gender distribution, and comorbidities. Patients with MSI-H CRC had significantly common O-blood group than control group (44.4% vs 18.1%, p: 0.001). In multivariate analysis, O-blood group was 4.2 times more common in the MSI-H patient group (95% CI: 1.514-11.819, p: 0.006). Also patients with MSI-H CRC were found to have significantly more right-sided, high-grade tumors and early-stage disease. CONCLUSIONS: MSI-H CRC is an important subgroup in colon cancer with different molecular and clinicopathological features. It was observed that O-blood group was 4.2 times more common in MSI-H CRC. We believe that clarifying the relationship between microsatellite instability and O-blood group and its possible genetic and epigenetic mechanisms in larger studies will enable us to better understand tumor behavior and prognosis, also affect our treatment choices of these patient groups.

Short-Course Radiotherapy Followed by Consolidation Chemotherapy Is Safe and Effective in Locally Advanced Rectal Cancer: Comparative Short-term Results of Multicenter Propensity Score Case-Matched Study.

BACKGROUND: Consolidation chemotherapy strategies have demonstrated improved pathological complete response and tumor downstaging rates for patients diagnosed with rectal cancer. OBJECTIVE: This study aimed to compare perioperative outcomes and pathological complete response rates among different neoadjuvant treatment strategies in patients undergoing total mesorectal excision for locally advanced rectal cancer. DESIGN: Propensity score case-matched study. SETTING: High-volume tertiary care centers. PATIENTS: Consecutive patients undergoing curative total mesorectal excision between January 2014 and June 2021 were queried. INTERVENTIONS: Patients were divided into 3 groups: long-course chemoradiation therapy with (N = 128) or without (N = 164) consolidation chemotherapy or short-course radiotherapy (N = 53) followed by consolidation chemotherapy. MAIN OUTCOME MEASURES: Demographics, preoperative tumor characteristics, histopathologic outcomes, and postoperative complication rates were reviewed and compared. Propensity score match analysis was conducted. RESULTS: A total of 345 patients (mean age: 58 ± 12 years; female: 36%) met the study inclusion criteria. Time interval from neoadjuvant treatment until surgery was longer for patients receiving consolidation chemotherapy ( p < 0.001). Pathological complete response rates were comparable among patients receiving long-course chemoradiation therapy (20.3%) and short-course radiotherapy with consolidation chemotherapy (20.8%) compared to long-course chemoradiation therapy alone (14.6%) ( p = 0.36). After the propensity score case-matched analysis, 48 patients in the long-course chemoradiation therapy with consolidation chemotherapy group were matched to 48 patients in the short-course radiotherapy with consolidation chemotherapy group. Groups were comparable with respect to age, sex, clinical stage, tumor location, type of surgical approach, and technique. Pathological complete response rate was comparable between the groups (20.8% and 18.8%, p = 0.99). LIMITATIONS: Study was limited by its retrospective nature. CONCLUSIONS: Among recent neoadjuvant treatment modalities, pathological complete response rates, and short-term clinical outcomes were comparable. Short-course radiotherapy with consolidation chemotherapy is safe and effective as long-course chemoradiation therapy as in a short-term period. See Video Abstract at http://links.lww.com/DCR/C174 . LA RADIOTERAPIA DE CORTA DURACIN SEGUIDA DE QUIMIOTERAPIA DE CONSOLIDACIN ES SEGURA Y EFICAZ EN EL CNCER DE RECTO LOCALMENTE AVANZADO RESULTADOS COMPARATIVOS A CORTO PLAZO DEL ESTUDIO MULTICNTRICO DE CASOS EMPAREJADOS POR PUNTAJE DE PROPENSION: ANTECEDENTES: Las estrategias de quimioterapia de consolidación han demostrado una mejor respuesta patológica completa y tasas de reducción del estadio del tumor para pacientes diagnosticados con cáncer de recto.OBJETIVO: Comparar los resultados perioperatorios y las tasas de respuesta patológica completa entre diferentes estrategias de tratamiento neoadyuvante en pacientes sometidos a escisión mesorrectal total por cáncer de recto localmente avanzado.DISEÑO: Estudio de casos emparejados por puntaje de propensión.ENTORNO CLINICO: Centros de atención terciaria de alto volumen.PACIENTES: Pacientes consecutivos sometidos a escisión mesorrectal total curativa por cáncer de recto localmente avanzado entre enero de 2014 y junio de 2021.INTERVENCIONES: Los pacientes se dividieron en tres grupos según la modalidad de tratamiento neoadyuvante: quimiorradioterapia de ciclo largo con (N = 128) o sin (N = 164) quimioterapia de consolidación o radioterapia de ciclo corto (N = 53) seguida de quimioterapia de consolidación.PRINCIPALES MEDIDAS DE RESULTADO: El punto final primario fue la respuesta patológica completa. Se revisaron y compararon los datos demográficos, las características preoperatorias del tumor, los resultados histopatológicos y las tasas de complicaciones posoperatorias entre los grupos de estudio. Se realizó un análisis de casos emparejados por puntaje de propensión.RESULTADOS: Un total de 345 pacientes (edad media de 58 ± 12 años y mujeres: 36%) cumplieron los criterios de inclusión del estudio. El intervalo de tiempo desde el tratamiento neoadyuvante hasta la cirugía fue mayor para los pacientes que recibieron quimioterapia de consolidación ( p < 0,001). Las tasas de respuesta patológica completa fueron comparables entre los pacientes que recibieron quimiorradioterapia de larga duración con quimioterapia de consolidación (20,3 %) y radioterapia de corta duración con quimioterapia de consolidación (20,8%) en comparación con la quimiorradiación de larga duración sola (14,6%) ( p = 0,36). Después del análisis de casos emparejados por puntaje de propensión, 48 pacientes en el grupo de quimiorradioterapia de ciclo largo con quimioterapia de consolidación se emparejaron con 48 pacientes en el grupo de radioterapia de ciclo corto con quimioterapia de consolidación. Los grupos fueron comparables con respecto a la edad, sexo, estadio clínico, ubicación del tumor, tipo de abordaje quirúrgico y la técnica. La tasa de respuesta patológica completa fue comparable entre los grupos (20,8% y 18,8%, p = 0,99). La morbilidad postoperatoria a los 30 días y las tasas de fuga anastomótica fueron similares.LIMITACIONES: El estudio estuvo limitado por su naturaleza retrospectiva.CONCLUSIONES: Entre las modalidades de tratamiento neoadyuvante recientes, las tasas de respuesta patológica completa y los resultados clínicos a corto plazo fueron comparables. La radioterapia de corta duración con quimioterapia de consolidación es segura y eficaz como terapia de quimiorradioterapia de larga duración en un período corto. Consulte Video Resumen en http://links.lww.com/DCR/C174 . (Traducción-Dr. Fidel Ruiz Healy ).

Enhancing the Anti-angiogenic Effect of Bevacizumab with ACE Inhibition on mCRC.

INTRODUCTION: Angiotensin 2 has been shown to promote angiogenesis through multiple pathways. Reduction of angiotensin 2 production by angiotensin-converting enzyme inhibitors (ACEi) could enhance the antiangiogenic effect of bevacizumab and lead to improved survival. METHODS: Data from metastatic colorectal cancer (mCRC) patients treated with bevacizumab in our hospital were retrospectively collected. Patients were divided into groups taking ACEi or angiotensin receptor blockers (ARB) or neither. We performed survival analysis and COX proportional hazard modelling and calculated the hazard ratio (HR). Multivariate analyses were performed to measure the impact of factors affecting survival, and subgroup analyses were performed for patients younger than 65 years. RESULTS: We enrolled 133 patients who received bevacizumab therapy. Eighty patients were male, and 53 were female. Twenty-three patients received ACEi treatment, and 34 patients received ARB. The median age was 58 years. Progression-free survival was higher in the ACEi group than in the ARB group or in the group receiving neither (7.66 vs. 5.98 vs. 5.0 months; p < 0.01), corresponding to a HR of 0.44 for the ACEi group (95% CI 0.26-0.74). Overall survival was not significantly longer in the ACEi group than in the ARB group or in the group receiving neither (22.0 vs. 23.5 vs. 19.7 months; p = 0.30), HR 0.66 (95% CI 0.38-1.2). In a subgroup analysis, overall survival was higher in patients younger than 65 years in the ACEi group (45.0 vs. 16.2 months; p = 0.02). CONCLUSION: In the final analysis, ACEi use in patients treated with bevacizumab resulted in prolonged progression-free survival, but this did not affect overall survival. Because our study is the first to look at the enhancement of the effect of bevacizumab by ACEi treatment and ACEi receiving patients are older, it would be useful to confirm our results by randomized trials.

The effect of primary tumour resection on patients with synchronous metastatic colorectal cancer treated with cetuximab-containing regimens.

BACKGROUND: This study aims to assess the effect of primary tumour resection (PTR) on patients with metastatic colorectal cancer (mCRC) treated with cetuximab. METHODS: This retrospective cohort study was conducted in a tertiary cancer center in Turkey. Patients with mCRC between January 2009 and December 2020 were extracted from the electronic hospital management system. Patients with RAS wild-type synchronous metastatic left-sided colon or rectum cancer who had cetuximab-containing treatment protocol were included in the study. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcome was response rates. RESULTS: A total of 111 patients with mCRC were included in this study. PTR was performed in 57.7% of all patients. Fifty-nine (53.2%) and 52 (46.8%) patients had rectal and left colon tumours, respectively. The combination treatment with cetuximab was FOLFIRI in 62.2% and FOLFOX in 29.7% of all patients. In subgroup analysis, the median PFS was 7.9 and 9 months in PTR (+) and PTR (-) patients, respectively. The difference between the groups was not statistically significant (P = 0.3). The median OS was 33 months in all patients. In subgroup analysis, the median OS was 39 and 27.9 months in PTR (+) and PTR (-) patients, respectively. The difference between the groups was statistically significant (P = 0.002). After adjusting for confounding factors, PTR and ECOG performance score were the independent prognostic factors for OS. CONCLUSION: PTR improved the OS in patients with RAS wild-type synchronous left-sided colon or rectum cancer treated with cetuximab-containing chemotherapy regimens.

Distributions and prognostic effects of ABO/Rh blood groups in patients with HER2/neu positive gastric and gastroesophageal junction cancer.

BACKGROUND: The aim of study was to look at ABO/Rh blood types frequency and prognostic significance in patients with HER2/neu positive gastric cancer. METHODS: The study was designed retrospectively. Clinicopathological characteristics, treatment approaches, and the ABO/Rh blood groups features were noted. The ABO/Rh blood types for patients and healthy donors were compared by the Chi-square method. RESULTS: The average age was 61 years. The average survival time was 17.9 months (13.2-22.5). ABO blood types frequencies were not similar between patients (25.9% O, 6.3% AB, 57.1% A, and 10.7% B) and control group (34.9% O, 7.9% AB, 41.9% A, and 15.3% B) (P = 0.01). Patients and controls had the same Rh factor distribution (P = 0.07). CONCLUSIONS: We showed that A blood group frequency was increased in patients with HER2/neu receptor-positive gastric cancer than in a healthy population. Also, we detected that the frequency of O blood type was decreased. ABO/Rh blood types were not linked with prognosis for overall survival.

Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study.

AIM: To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib. METHODS: We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients. RESULTS: There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group. CONCLUSION: This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.

Chronic hyperglycemia based on diabetes is independently associated with decreased survival in patients with advanced cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have started a new era in treating patients with cancer. The effect of comorbidities and concomitant drug use on ICIs have become of interest in those patients. Data about the impact of hyperglycemia on response to ICIs in cancer patients are limited. All advanced-stage cancer patients treated with ICIs in Ankara University Medical Oncology Department were retrospectively evaluated. Patients treated in expanded access programs or clinical trials were excluded from the study. A total of 137 patients were included in this study. The most common primary tumor type was malign melanoma (32.8%) and nivolumab (62.3%) was the most common used ICI. More than half of patients (57.7%) had lung metastasis at the initiation of ICIs. Thirty-five patients (25.5%) had diabetes before initiating ICIs. Median baseline fasting glucose level was higher in patients with diabetes than those without diabetes (117 mg/dl vs. 99 mg/dl, P = 0.002). In all patients, median overall survival and progression-free survival were 11.3 [95% confidence interval (CI), 8.1-14.4) and 5.9 (95% CI, 3.6-8.3) months, respectively. In multivariate analysis, diabetes was found to increase risk of death [hazard ratio (HR), 2.09; 95% CI, 1.27-3.43, P = 0.004) and disease progression (HR, 2.01, 95% CI, 1.29-3.09, P = 0.002). Hyperglycemia might decrease response to ICIs in patients with advanced cancer. This research area is still an unmet need in the immunotherapy era. Prospective studies are needed to elucidate the effect of hyperglycemia on the response to ICIs.

The relationship between clinicopathological parameters and PD-L1 expression level in advanced stage non-small cell lung cancer.

Introduction: Clinicopathological parameters related to programmed death ligand 1 (PD-L1) expression levels have been investigated in several studies. However, the results of these studies are conflicting and vary in different populations. This study aimed to investigate the relation of clinicopathological parameters with PD-L1 expression level in advanced stage non-small cell lung cancer patients. Materials and Methods: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The data of clinicopathological parameters was collected. Clinicopathological parameters in relation to PD-L1 expression levels (0%, 1-50%, and >50%) were analyzed as univariable and multivariable. Result: In total, 384 patients were enrolled. PD-L1 expression in tumor cells was between 1-50%, and >50% in 41.4%, and 23.4% of patients, respectively. There was no PD-L1 expression in 35.2% of the patients. In univariable analysis, we found that the parameters associated with PD-L1 expression levels revealed that metastatic site number, the subtype of cancer, diagnostic material type, platelet number, and LDH level were statistically significant. Adenocarcinoma frequency was higher in tumors that had PD-L1 expression >50% than in tumors that did not express PD-L1 and the difference was statistically significant (p= 0.04, coefficient= 0.3, 95% CI 0.09-0.94). Cytology as diagnostic material was significant in PD-L1 level 1-50% comparing to >50% (p= 0.02, coefficient= 2.2, 95% CI= 1.08-4.46). Conclusions: According to the results of our study, many of the clinicopathological parameters are not related to the PD-L1 level. The histological subtype and diagnostic material may affect the level of PD-L1 expression.

Prognostic role of pan-immune-inflammation value in patients with metastatic castration-resistant prostate cancer treated with androgen receptor-signaling inhibitors.

AIM: To assess the prognostic effect of pan-immune inflammation value (PIV) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) or enzalutamide. METHODS: Patients with mCRPC treated with AA or enzalutamide between January 2010 and June 2021 were included in this study. The most recently examined complete blood count values in the 1-month period before treatment were used for calculating PIV. The relationship between overall survival (OS) and PIV was evaluated by multivariate analysis. By using PIV and lactate dehydrogenase (LDH) levels which had shown survival effect at multivariate analysis, PIV-LDH combined score was established. RESULTS: A total of 114 patients were included in this study. At the median follow-up of 34.6 months (95% confidence interval [CI]: 32.4-36.8), the median OS was 21 months (95% CI: 17.6-21.3). The median OS in the low-PIV group was significantly higher than in the high-PIV group (34.4 months (95% CI: 21.3-47.5) vs. 14.3 months (95% CI: 10.0-18.7), p < 0.001). In the multivariate analysis for OS, high PIV (hazard ratio [HR]: 1.86, 95% CI: 1.11-3.13, p = 0.018) and LDH value 1.5 times the upper limit of normal and above (HR: 3.65 95%, CI: 1.86-7.16, p < 0.001) were associated with shorter OS. When survival analysis was performed according to the PIV-LDH combined score, the median OS was 34.4 months (95% CI: 22.2-46.6) in the low-risk group, 17.7 months (95% CI: 11.7-23.6) in the intermediate-risk group, and 8.4 months (95% CI: 5.1-11.7) in the high-risk group (p < 0.001). The C-index of the combined PIV-LDH score was higher than the C-index of PIV (0.65 vs. 0.61). CONCLUSION: In this study, we demonstrated that PIV was an independent prognostic factor for OS in patients with mCRPC treated with AA or enzalutamide. Additionally, PIV-LDH combined score may be considered a promising composite peripheral blood-based biomarker to predict OS in those patients.

Genomic Landscape of Actionable Mutations in Primary and Metastatic Tissues of Colon Adenocarcinoma.

Aim To assess the actionable genomic landscape of colon adenocarcinoma in the primary and metastatic tumor tissues. Methods The data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) were used in this study. Colon adenocarcinoma patients with primary and metastatic tissue samples (distant organ and lymph node) were selected. Patients with samples from a local recurrence, not otherwise specified tumor samples, and data not collected for sampling localization were excluded. Results A total of 3286 and 1727 patients were included in the primary and metastatic tissue sample groups, respectively. There was no difference between the groups in Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation rates. The rates of v-Raf murine sarcoma viral oncogene homolog B (BRAF) and mismatch repair (MMR) gene mutations were higher in the primary tumor tissues than in the metastatic tumor tissues. There was also no difference between the groups in other actionable gene alterations (e.g. ERBB2 amplification and neurotrophic receptor tyrosine kinase (NTRK) 1 and NTRK3 fusions). In contrast to all cohorts, in Asian and black patients, there was no difference in actionable genomic landscape between the primary and metastatic tumor tissues. Conclusion This study had the largest number of colon cancer patients that evaluated the actionable genomic alterations in primary and metastatic tumor tissues. BRAF and MMR gene alterations were more frequent in the primary tumor tissues than the metastatic tumor tissues.

The prognostic role of polypharmacy in metastatic colorectal cancer patients treated with regorafenib.

Aim: To evaluate polypharmacy (PP) in patients with metastatic colorectal cancer receiving regorafenib. Methods: Patients with metastatic colorectal cancer receiving regorafenib were included and divided into two categories by their PP status: PP- (<5 regular drug use/day) and PP+ (≥5 regular drug use/day). Results: 80 patients were included. 31 (38.7%) patients had PP. The median number of drugs used was three and seven in PP- and PP+ patients, respectively. Antiemetics (26.5%) and antacids (48.4%) were the most common drugs used by PP- and PP+ patients, respectively. In multivariate analysis, the risk of death was higher in PP+ patients (hazard ratio: 2.1; 95% CI: 1.2-3.7; p = 0.005). Conclusion: PP was an independent prognostic factor for overall survival in patients with metastatic colorectal cancer receiving regorafenib.

Regorafenib is a targeted therapy option that is used in patients with chemotherapy-refractory metastatic colorectal cancer. Because of the chemotherapy-refractory stage of the disease, patients are prone to use more medications for symptom palliation. Polypharmacy (PP) refers to the drug burden in an individual, and the use of five or more drugs in a day is usually considered to represent PP. In this study, the authors assessed the impact of PP in patients with metastatic colorectal cancer treated with regorafenib. The authors' study found that PP had a negative impact on survival outcomes in these patients. This is why inappropriate drug use should be assessed at each visit and the medication discontinued if it is not an essential part of the treatment.

Key considerations and common adverse events for HIV-positive patients with cancer treated with immune checkpoint inhibitors.

HIV-infected patients are more susceptible to cancer due to their immune-compromised condition and HIV infection. Chronic inflammation and immune dysregulation are the main causes of cancer development in these patients. Because of lymphopenia and an immune-compromised condition, most HIV-infected patients with cancer were not considered for cytotoxic therapies, such as chemotherapy and radiotherapy. Immune checkpoint inhibitors (ICIs) have become a game-changer in many cancer types. However, not enough prospective data is available regarding the use of ICIs in HIV-infected patients with cancer. Retrospective data from case reports/series showed that ICIs are safe in HIV-infected patients with cancer.

Systemic Immune-Inflammation Index as a Prognostic Marker of Late Recurrence in Operable Gastric Cancer: a Dual-Center Study.

AIM: To evaluate the prognostic role of the systemic immune-inflammation index (SII) in patients with operable gastric cancer. METHODS: We assessed 354 patients with operable gastric cancer from tertiary centers in Turkey. SII was calculated by following formula: [neutrophil (cells × 109/L) × platelet (cells × 109/L)]/lymphocyte (cells × 109/L). The best cut-off value for SII was determined by using "receiver operating characteristics (ROC)" analysis. We used log-rank and Cox-regression analysis for survival analyses. RESULTS: One hundred twenty patients were in the late recurrence group (recurrences have developed 36 months after the surgery). SII was not a prognostic factor in the early recurrence group. However, relapse-free survival (RFS) was longer in SII-low patients than SII-high patients in the late recurrence group. In multivariable analysis, SII was the only independent prognostic factor for RFS in the late recurrence group (hazard ratio (HR): 5.42, 95% CI: 1.18-24.82, p = 0.03). CONCLUSION: SII was an independent prognostic factor for RFS in GC patients with late recurrence. Late recurrence risk was higher in SII-high patients than SII-low patients. Inflammation contributes to tumor progression, invasion, and metastasis. Prolonged exposure to chronic inflammation could explain the results of this study.

Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study.

BACKGROUND: The role of radiotherapy in the adjuvant treatment of gastric cancer (GC) remains to be elucidated. This study aimed to assess the additional benefit of radiotherapy in the adjuvant treatment of GC. MATERIALS AND METHODS: In this retrospective cohort study, we included 230 gastric adenocarcinoma patients who underwent D2 dissection between January 2004 and December 2019. Patients without R0 resection, who underwent metastasectomy at surgery, and treated with the neoadjuvant treatment were excluded. The co-primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were the locoregional and distant metastasis risk and adverse events (AEs) leading to treatment discontinuation. RESULTS: One hundred and sixty-six and 64 patients were included in the chemoradiotherapy (CRT) and chemotherapy (ChT) arms, respectively. The median OS was 135.8 months [interquartile range (IQR): 99.4-172.2] and 97 months (IQR: 59.7-134.3) in the CRT and the ChT arms, respectively. No statistical significance was observed between the arms in OS (p = 0.3). Locoregional or distant recurrence rates were similar in each group. AEs leading to treatment discontinuation were higher in the CRT arm than in the ChT arm (13.2 vs 9.3%), and the difference between the arms was not statistically significant (p = 0.4). CONCLUSION: In this real-life study, we established that there was no additional benefit of RT in GC patients who underwent D2 dissection. HOW TO CITE THIS ARTICLE: Yekedüz E, Dogan I, Birgi SD, et al. Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study. Euroasian J Hepato-Gastroenterol 2021;11(2):51-58.

Efficacy and tolerability of vismodegib treatment in locally advanced and metastatic basal cell carcinoma: Retrospective real-life data.

The study aims to evaluate the vismodegib treatment in local advanced (laBCC) and metastatic (mBCC) basal cell carcinoma. The data of 29 patients were retrospectively reviewed. The clinical and histopathological features of the patients and adverse events of vismodegib were recorded. Overall survival (OS) and progression-free survival (PFS) were evaluated with Kaplan-Meier analysis. The median follow-up period was 17 months (range: 1.6-57.3), and the median age at diagnosis 73 years (range: 39-88). The most common disease location was head and neck (86.2%), and the most common non-skin sites of disease were lymph nodes (13.8%), bone (13.8%), lung (6.9%), and brain (6.9%). Three (10.3%) patients had Gorlin's syndrome. The number of metastatic patients was 5 (17.2%). With vismodegib treatment, the complete response rate was 27.6%, partial response 55.2%, and stable response 10.3%. Treatment responses were most frequently seen within 2 months from the beginning of vismodegib. The median OS was 43.3 ± 9.0 months (25.6-61.1) for all patients. The median PFS in the laBCC was 15.7 ± 1.8 months (12.2-19.3), and 12.1 ± 4.6 months (2.9-21.2) in the mBCC. In the univariable analysis for the OS, only the treatment after the vismodegib was statistically significant, showing chemotherapy was better comparing to no treatment or surgery. The most common adverse events were fatigue-58.6%, muscle spasms-48.3%, alopecia-13.8%, and weight loss-13.8%. This real-life data study shows that vismodegib treatment in locally advanced and metastatic BCC was well tolerated and effective.