Albumin-myosteatosis gauge as a prognostic factor in patients with advanced pancreatic cancer undergoing first-line chemotherapy.

BACKGROUND: Sarcopenia and myosteatosis have been associated with a poor prognosis for several cancers. The albumin-myosteatosis gauge (AMG) is a novel integrated measure proposed to assess myosteatosis along with serum albumin level as a surrogate of systemic inflammation and malnutrition. The aim of this study was to investigate the prognostic value of AMG in patients with advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with advanced PDAC treated with chemotherapy between 2013 and 2022 were evaluated. Skeletal muscle radiodensity (SMD) and skeletal muscle index (SMI) were calculated using computed tomography at the level of the L3 vertebra. The AMG was defined as albumin x SMD and expressed as an arbitrary unit (AU). Patients were first categorized by sex-specific quartiles and then dichotomized at the sex-specific median value of the AMG. RESULTS: A total of 196 patients were included. The median age (interquartile range) was 62 (54-67), and 128 (65.3%) were male. With regard to AMG, 142.86 and 114.15 AU were identified as cutoff values for males and females, respectively. In multivariable analyses, lower AMG values (G1-G2 vs. G3-G4) (HR: 1.61, 95% CI 1.17-2.21, p = 0.003), higher ECOG performance score (> 0 vs. 0) (HR: 1.51, 95% CI 1.10-2.06, p = 0.009) and metastatic disease (vs. locally advanced) (HR: 1.88, 95% CI 1.27-2.79, p = 0.001) were associated with OS. CONCLUSION: The study findings suggest the prognostic value of AMG in patients with advanced PDAC undergoing first-line chemotherapy. Further studies are warranted to validate these findings and assess potential predictive role of AMG in guiding treatment selection.

Sirolimus experience in adult patients with vascular malformations.

AIM: Sirolimus, a mammalian target of rapamycin inhibitor, inhibits cell growth and proliferation by controlling ribosome biogenesis and protein synthesis in vascular anomalies and cancers. However, most sirolimus studies on vascular anomalies were conducted in the pediatric population, with limited data in adults. In this study, we assessed the effectiveness and safety of sirolimus in adult patients with vascular malformation, a subtype of vascular anomaly. METHODS: We conducted a retrospective analysis of adult vascular malformation patients aged over 16, treated at Hacettepe University Cancer Institute from January 2013 to September 2022. Patient demographics and clinical characteristics were recorded. The primary outcome was the efficacy of sirolimus evaluated by response and disease control rates. The disease control rate was defined as the cumulative percentage of complete or partial responses, along with stable disease. The secondary endpoint was toxicity and safety. RESULTS: 38 patients with a median age of 21 (IQR: 18-33) were recruited. Prior to sirolimus treatment, 57.9% of patients had undergone other therapeutic interventions, predominantly sclerotherapy and surgery. The median follow-up time during sirolimus treatment was 18.5 (IQR: 11.3-74.5) months. The disease control rate was 92.1% (35/38). Head-neck localization was associated with better response rates (p = .001). Sirolimus was generally well tolerated and grade 1 or 2 oral mucositis (n = 4) and skin rash (n = 3) were the most common side effects. CONCLUSION: In this study, we found sirolimus was efficacious and well tolerated in adult patients with vascular malformation.

Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

Sonographic Measurements of Rectus Femoris Muscle Thickness Strongly Predict Neutropenia in Cancer Patients Receiving Chemotherapy.

The objective of this study was to explore the possible association between low skeletal muscle mass (SMM)-assessed by computed tomography (CT) and ultrasound (US)-and hematologic toxicity in cancer patients. A prospective cohort study was conducted in cancer patients who received anthracycline-based chemotherapy between 2018 and 2020 and who had baseline abdominal CT including L3 level for measuring SMM. Regional muscle measurements were carried out using US. A total of 65 patients (14 males, 51 females) were included. ROC (receiver operating characteristic) analysis identified threshold values of 18.0 mm [AUC (area under the curve) = 0.765] for females and 20.0 mm (AUC = 0.813) for males, predicting severe neutropenia. Using these cut-offs, females with low rectus femoris (RF) thickness (<18.0 mm) had a significantly higher incidence of grade ≥3 neutropenia (50.0% vs. 10.8%, p = 0.005), and males with low RF values (<20.0 mm) had a higher incidence (80.0% vs. 22.2%, p = 0.063). A regression analysis, irrespective of age, gender, and body mass index, revealed that only low RF muscle thickness increased the risk of grade 3-4 neutropenia by 9.210 times (95% CI = 2.401-35.326, p = 0.001). Utilizing US to measure RF muscle thickness aids in identifying cancer patients at an elevated risk of developing neutropenia. Needless to say, US can serve as a convenient and easily accessible tool for assessing low SMM, providing repeat point-of-care evaluations in clinical practice.

Twelve-month progression-free survival with sotorasib and panitumumab in KRAS G12C mutant metastatic colorectal cancer.

Colorectal cancer (CRC) ranks third in global cancer prevalence, with 40% presenting as metastatic colorectal cancer (mCRC). KRAS mutations in mCRC patients confer resistance to anti-EGFR treatments. Promising inhibitors such as sotorasib and adagrasib targeting KRASG12C mutations have demonstrated efficacy. Herein, we present a heavily pretreated mCRC case with a progression-free survival of 12 months with sotorasib and panitumumab. In 2017, a 27-year-old male presented with abdominal pain and received a diagnosis of stage IIIC KRAS G12C mutant CRC. Following surgery and adjuvant chemotherapy, he developed metastases in the liver and lungs in 2020. Treatment with FOLFIRINOX and bevacizumab, and later FOLFIRI and bevacizumab, with surgeries and local interventions resulted in partial responses. Upon disease progression, sotorasib and panitumumab were initiated, achieving a complete metabolic response. After 12 months of progression-free survival, oligoprogressive liver lesions were surgically resected. This case highlights the remarkable outcome of a heavily treated KRAS G12C mutant mCRC patient. The combination of sotorasib and panitumumab, along with multidisciplinary approaches including surgery and local interventions, played an important role in our patient's survival.

Acute heart failure following pazopanib treatment: a literature review featuring two case reports.

Tyrosine kinase inhibitors (TKIs) have transformed cancer treatment but are associated with cardiovascular toxicity, including heart failure. This review examines the cardiotoxicity of pazopanib, a VEGFR-TKI, through two case reports and explores potential mechanisms. The importance of vigilant clinical monitoring to prevent cardiac dysfunction in cancer patients receiving pazopanib is emphasized. We present two cases of acute heart failure following pazopanib treatment. Case 1 involves a comorbidity-free, 62-year-old woman with metastatic renal cell carcinoma who experienced irreversible heart failure. In case 2, a 40-year-old woman with a history of anthracycline-containing chemotherapy developed reversible left ventricular systolic dysfunction following pazopanib discontinuation. Both patients received appropriate management for their heart failure symptoms. Case 1's condition rapidly deteriorated, leading to her unfortunate demise 3 months after starting pazopanib. In contrast, case 2's cardiac function improved after discontinuing pazopanib. The advent of TKIs has revolutionized cancer treatment, but their association with cardiovascular toxicity necessitates meticulous monitoring of patients. The cases presented here highlight the importance of recognizing and managing cardiotoxicity, particularly in patients without prior cardiovascular risk factors. Understanding the underlying mechanisms and risk factors for TKI-induced heart failure is crucial to optimize patient care and treatment outcomes. Oncologists should be vigilant in identifying clinical symptoms and closely monitoring cardiac function throughout TKI therapy.

Mean Platelet Volume to Lymphocyte Ratio: A New Biomarker Predicting Response in Patients with Solid Tumors Treated with Nivolumab.

Introduction: Although immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, identifying factors that predict treatment response remains a challenge in clinical practice. There is a need for biomarkers to identify patients who may not benefit from these treatments. It is crucial to identify a simple and cost-effective biomarker that can be easily incorporated into clinical practice. This study aims to investigate the mean platelet volume to lymphocyte ratio (MPVLR), as measured by a hemogram test, and median overall survival (mOS) in patients with cancer treated with nivolumab. Methods: A total of 131 adult patients with metastatic cancer, including malignant melanoma (MM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and head and neck cancer (HNC), were included in this study. Baseline demographics, ECOG (Eastern Cooperative Oncology Group) performance status, tumor type, and blood count parameters were recorded. Univariate and multivariate analyses were conducted to evaluate potential risk factors. Results: The median age of the patients was 59.87 ± 11.97 years, and the median follow-up period was 20.20 months (IQR, 12.80-27.60). RCC (43.5%) and MM (25.9%) were the most common diagnoses. Patients with ECOG scores of 0-1 had a longer mOS than those with scores of 2-3 (mOS: 20.60 months [95% CI, 14.94-25.29] vs. 5.24 months [95% CI, 0-16.42], p < 0.001). Additionally, patients with lactate dehydrogenase (LDH) levels within the normal range had a longer mOS than those with high LDH levels (mOS: 24.54 months [95% CI, 14.13-34.96] vs. 13.10 months [95% CI, 4.49-21.72], p = 0.038). Patients with low MPVLR also had a longer mOS than those with high MPVLR (mOS: 33.70 months [95% CI, 25.99-41.42] vs. 11.07 months [95% CI, 6.89-15.24], p < 0.001). In the multivariate Cox regression analysis, high MPVLR, ECOG score of 2-3, and high LDH level were associated with shorter mOS (p < 0.001, p = 0.001, and p = 0.046, respectively). Conclusion: This study demonstrates that MPVLR could serve as a novel biomarker for predicting response to nivolumab treatment. Incorporating MPVLR into clinical practice may aid in identifying patients who are less likely to benefit from the treatment.

Seven-Year Single-Center Experience of the Efficacy and Safety of Ferric Carboxymaltose in Cancer Patients with Iron-Deficiency Anemia.

Anemia remains an essential concern affecting the quality of life and the survival of cancer patients. Although there are different approaches to treating anemia in cancer patients, the number of studies reporting the efficacy of iron replacement in cancer patients is limited. In this study, the efficacy and safety of iron carboxymaltose, a parenteral iron treatment option, in the treatment of anemia, were examined retrospectively. A total of 1102 adult patients who received IV ferric carboxymaltose treatment at Hacettepe Oncology Hospital between 2014 and 2020 were included. The mean hemoglobin change observed at the end of the 12th week was 1.8 g/dL, and the rate of patients with an increase in hemoglobin of 1 g/dL or more was 72.1%. It was observed that the treatment demonstrated effectiveness in patients receiving active cancer treatment in all tumor types. The treatment was generally safe, and no grade 3-5 side effects were observed in the patients included in the study. According to one of the most extensive series published in the literature, iron carboxymaltose is an efficient and safe alternative for cancer patients with iron-deficiency anemia.

The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter real-world study from Turkey.

The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22-89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4-33.3) months, the median PFS and OS were 5.1 (95% CI: 3-7.3) and 18.1 (95% CI: 6.2-29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.

Advances in the Early Detection of Hepatobiliary Cancers.

Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early diagnosis is crucial and can significantly improve survival rates through curative treatment approaches. Current guidelines recommend abdominal ultrasonography (USG) and alpha-fetoprotein (AFP) monitoring for HCC screening in high-risk groups, and abdominal USG, magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) monitoring for biliary tract cancer. However, despite this screening strategy, many high-risk individuals still develop advanced-stage HCC and BTC. Blood-based biomarkers are being developed for use in HCC or BTC high-risk groups. Studies on AFP, AFP-L3, des-gamma-carboxy prothrombin, glypican-3 (GPC3), osteopontin (OPN), midkine (MK), neopterin, squamous cell carcinoma antigen (SCCA), Mac-2-binding protein (M2BP), cyclic guanosine monophosphate (cGMP), and interleukin-6 biomarkers for HCC screening have shown promising results when evaluated individually or in combination. In the case of BTCs, the potential applications of circulating tumor DNA, circulating microRNA, and circulating tumor cells in diagnosis are also promising. These biomarkers have shown potential in detecting BTCs in early stages, which can significantly improve patient outcomes. Additionally, these biomarkers hold promise for monitoring disease progression and evaluating response to therapy in BTC patients. However, further research is necessary to fully understand the clinical utility of these biomarkers in the diagnosis and management of HCC and BTCs.

Prognostic and predictive value of tumor infiltrating lymphocytes in combination with systemic inflammatory markers in colon cancer.

OBJECTIVE: Systemic inflammatory indices and CD8(+) tumor infiltrating lymphocytes (TILs) in the tumor microenvironment are highly prognostic in colon cancer (CC) but combined assessment is less well studied. The purpose of this study was to investigate the prognostic and predictive value of CD8(+) TILs in combination with systemic inflammatory indices in patients with resected stage II-III colon cancer. PATIENTS AND METHODS: Patients with stage II-III CC (n = 304) diagnosed between 2008 and 2016 were included. Pan-immune inflammation value (PIV) was used as a comprehensive inflammatory index and was calculated as: [neutrophil count × platelet count × monocyte count]/lymphocyte count. The mean density of CD8+ TILs in the periphery and center of the tumor was assessed and dichotomized at the 75th percentile. Combined inflammation score (CIS) was classified as "high" in patients with high PIV (>median) plus low mean CD8(+) TILs density, and CIS "low" in the remaining patients. RESULTS: 5-year DFS was 71% (78% in stage II, 63.4% in stage III). PIV was higher in right colon tumors, T4 tumors and in patients with obstruction / perforation. CD8(+) TIL density was lower in node positive tumors. High PIV and low CD8(+) TILs were associated with shorter disease-free survival (DFS). In multivariate analysis; age > 65 years, stage III disease and high CIS (PIVhigh / CD8low) were associated with shorter DFS. Among patients with stage II disease, patients with high CIS (PIVhigh / CD8low) derived significant benefit from adjuvant chemotherapy while those with low CIS derived no benefit. CONCLUSION: Combined inflammation score may represent a new prognostic factor for localized colon cancer and predictor of chemotherapy response in patients with stage II disease.

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry.

INTRODUCTION: This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. METHODS: HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug (bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). RESULTS: Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6 years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26-67), and the median age at the HM diagnosis was 55.5 (range, 38-76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35-7.05). Ten patients with HM were under 65 years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88-11.43) and women (SIR 4.76, 95% CI 1.74-10.55). CONCLUSIONS: The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

Optimal adjuvant treatment strategies for TNBC patients with residual disease after neoadjuvant treatment.

INTRODUCTION: The therapeutic armamentarium for the neoadjuvant treatment of triple-negative breast cancer (TNBC) has significantly expanded with the hopes of improving pathological complete response (pCR) rates and the possibility of a cure. However, the data on optimal adjuvant treatment strategies for patients with residual disease after neoadjuvant treatment is limited. AREAS COVERED: We discuss the available data on adjuvant treatment for residual TNBC after neoadjuvant treatment considering clinical trials. Additionally, we discuss ongoing trials to give perspectives on how the field may evolve in the next decade. EXPERT OPINION: The available data support the use of adjuvant capecitabine for all patients and either adjuvant capecitabine or olaparib for patients with germline BRCA1 and BRCA2 mutations, according to availability. The CREATE-X study of capecitabine and OlympiA study of olaparib demonstrated disease-free and overall survival benefits. There is an unmet need for studies comparing these two options for patients with germline BRCA mutations. Further research is needed to delineate the use of immunotherapy in the adjuvant setting, molecular targeted therapy for patients with molecular alterations other than germline BRCA mutation, combinations, and antibody-drug conjugates to further improve outcomes.

Molecularly imprinted electrochemical sensor for the selective and sensitive determination of octreotide in cancer patient plasma sample.

In this study, a molecularly imprinted polymer film (P (ANI)@MIP) on the electrode surface was fabricated using aniline as a functional monomer and octreotide (OC) as a template molecule. The developed P (ANI)@MIP was electrochemically electropolymerized on a glassy carbon electrode (GCE) surface. Each step of MIP production was evaluated by viewing the [Fe (CN)6]3-/4- signal obtained using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The P (ANI)@MIP film layer was studied with a scanning electron microscope (SEM), Raman, and contact angle measurements. The parameters consisting of monomer, template ratio, cycle number, removal solution, removal time, and rebinding time were optimized to obtain the best electrochemical sensor. The developed method was validated in line with ICH guidelines. The linear range, LOD, and LOQ were found as 10-80 fM, 0.801 fM, and 2.670 fM, respectively. The selectivity of the method was tested with the response of somatostatin and lanreotide from the same growth hormone family by comparing the OC response. The developed P (ANI)@MIP/GCE sensor is the first reported method for electrochemical analysis of OC. The P (ANI)@MIP/GCE sensor exhibited high sensitivity and selectivity for OC. The novel MIP sensor was used to determine OC in cancer patient plasma samples. The concentration of OC in cancer patients varied between 8.98 ng/mL and 10.10 ng/mL.

A meta-analysis of the association between adjuvant chemoradiotherapy and disease-free survival in gastric cancer according to the histology.

BACKGROUND: There are biological distinctions between gastric cancers from Eastern and Western nations, and therapeutic strategies may differ regionally. Perioperative chemotherapy, adjuvant chemotherapy, and adjuvant chemoradiotherapy (CRT) have all been demonstrated to be effective in the treatment of gastric cancer. The goal of this study was to do a meta-analysis of published studies that were eligible to see if adjuvant chemoradiotherapy was helpful for gastric cancer based on the cancer's histology. METHOD: From inception to May 4, 2022, manual searches were conducted to identify all eligible literature using the PubMed database for the published phase III clinical trial and a randomize-controlled trial testing the role of adjuvant chemoradiotherapy in operable gastric cancer. RESULTS: Two trials with a total of 1004 patients were selected as a result. Adjuvant CRT was found to have no effect on disease-free survival (DFS) in gastric cancer patients treated with D2 surgery (HR: 0.70 (0.62-1.02), p: 0.07). However, patients with intestinal-type gastric cancers exhibited significantly longer DFS (HR: 0.58 (0.37-0.92), p = 0.02). DISCUSSION: After D2 dissection, adjuvant CRT improved DFS in patients with intestinal-type gastric cancers but not in those with diffuse-type gastric cancers.

Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer.

OBJECTIVE: DNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC. PATIENTS AND METHODS: Patients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed. RESULTS: 130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48-9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04-3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13-5.48, p = 0.023) and high post-operative CA 19-9 level (>100 IU/ml) (HR:2.61 95% CI 1.40-4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53. CONCLUSION: Contrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.

Emerging treatment strategies in hepatobiliary cancer.

INTRODUCTION: There have been significant advances in the treatment of hepatobiliary cancers, especially for advanced-stage disease. However, data is limited for optimal therapy selection in the first line and sequencing of available options. AREAS COVERED: This review covers the systemic treatment of hepatobiliary cancers with an emphasis on the advanced stage. The previously published and ongoing trials will be discussed to create an algorithm for the current practice and to give future perspectives on how the field could go forward. EXPERT OPINION: While there is no standard-of-care option in the adjuvant treatment of hepatocellular cancer, capecitabine is the standard of care for biliary tract cancer. The efficacy of adjuvant gemcitabine and cisplatin and the added benefit of radiotherapy to chemotherapy are yet to be defined. For the advanced stage, immunotherapy-based combinations became the standard of care for both hepatocellular and biliary tract cancers. The molecularly targeted therapy has profoundly changed the second-line and later treatment for biliary tract cancers, while the optimal second-line treatment for advanced hepatocellular cancer is yet to be defined due to rapid advances in the first-line setting.

The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.