A novel fluorescent c-met targeted imaging agent for intra-operative colonic tumour mapping: Translation from the laboratory into a clinical trial

BackgroundThe c-Met protein is overexpressed in many gastrointestinal cancers. We explored EMI-137, a novel c-Met targeting fluorescent probe, for application in fluorescence-guided colon surgery, in HT-29 colorectal cancer (CRC) cell line and an in vivo murine model.MethodsHT-29 SiRNA transfection confirmed specificity of EMI-137 for c-Met. A HT-29 CRC xenograft model was developed in BALB/c mice, EMI-137 was injected and biodistribution analysed through in vivo fluorescent imaging. Nine patients, received a single intravenous EMI-137 bolus (0.13 mg/kg), 1–3 h before laparoscopic-assisted colon cancer surgery (NCT03360461). Tumour and LN fluorescence was assessed intraoperatively and correlated with c-Met expression in eight samples by immunohistochemistry.Findingsc-Met expression HT-29 cells was silenced and imaged with EMI-137. Strong EMI-137 uptake in tumour xenografts was observed up to 6 h post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all participants, 4/9 showed increased tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15/15) exhibited high c-Met protein expression.InterpretationEMI-137, binds specifically to the human c-Met protein, is safe, and with further refinement, shows potential for application in fluorescence-guided surgery.     

Can physical prehabilitation prevent complications after colorectal cancer surgery in frail older patients?

IntroductionFrail patients with colorectal cancer (CRC) are at increased risk of complications after surgery. Prehabilitation seems promising to improve this outcome and therefore we evaluated the effect of physical prehabilitation on postoperative complications in a retrospective cohort of frail CRC patients.MethodsThe study consisted of all consecutive non-metastatic CRC patients ≥70 years who had elective surgery from 2014 to 2019 in a teaching hospital in the Netherlands, where a physical prehabilitation program was implemented from 2014 on. We performed both an intention-to-treat and per protocol analysis to evaluate postoperative complications in the physical prehabilitation (PhP) and non-prehabilitation (NP) group.ResultsEventually, 334 elective patients were included. The 124 (37.1%) patients in the PhP-group presented with higher age, higher comorbidity scores and walking-aid use compared to the NP-group. Medical complications occurred in 26.6% of the PhP-group and in 20.5% of the NP-group (p = 0.20) and surgical complications in 19.4% and 14.3% (p = 0.22) respectively. In all frailty subgroups, the medical complications were lower in the PhP-group compared to the NP-group (35.9% vs. 45.5% for patients with ≥2 comorbidities, 36.2% vs. 39.1% for ASA score ≥ III, 29.2% vs. 45.8% for walking-aid use). Differences were not significant.ConclusionsIn this study, patients selected for physical prehabilitation had a worse frailty profile and therefore a higher a priori risk of postoperative complications. However, the postoperative complication rate was not increased compared to patients who were less frail at baseline and without prehabilitation. Hence, physical prehabilitation may prevent postoperative complications in frail CRC patients ≥70 years.     

Survival of surgical and non-surgical older patients with non-metastatic colorectal cancer: A population-based study in the Netherlands

BackgroundSurgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are largely unknown.ObjectiveTo examine the characteristics and survival of surgical and non-surgical older patients with non-metastatic CRC in the Netherlands.MethodsAll patients aged ≥70 years and diagnosed with non-metastatic CRC between 2014 and 2018 were identified in the Netherlands Cancer Registry. Patients were divided based on whether they underwent surgery or not. Three-year overall survival (OS) and relative survival (RS) were calculated for both groups separately. Relative survival and relative excess risks (RER) of death were used as measures for cancer-related survival.ResultsIn total, 987/20.423 (5%) colon cancer patients and 1.459/7.335 (20%) rectal cancer patients did not undergo surgery. Non-surgical treatment increased over time from 3.7% in 2014 to 4.8% in 2018 in colon cancer patients (P = 0.01) and from 17.1% to 20.2% in rectal cancer patients (P = 0.03). 3 year RS was 91% and 9% for surgical and non-surgical patients with colon cancer, respectively. For rectal cancer patients this was 93% and 37%, respectively. In surgical patients, advanced age (≥80 years) did not decrease RS (colon; RER 0.9 (0.7–1.0), rectum; RER 0.9 (0.7–1.1)). In non-surgical rectal cancer patients, higher survival rates were observed in patients treated with chemoradiotherapy (OS 56%, RS 65%), or radiotherapy (OS 19%, RS 27%), compared to no treatment (OS 9%, RS 10%).ConclusionNon-surgical treatment in older Dutch CRC patients has increased over time. Because survival of patients with colon cancer is very poor in the absence of surgery, this treatment decision must be carefully weighed. (Chemo-)radiotherapy may be a good alternative for rectal cancer surgery in older frail patients.     

Pre-treatment 18F-RGD Uptake may Predict Adverse Events during Apatinib Antiangiogenic Therapy

AimsThe adverse events during antiangiogenic therapy inevitably influence a patient's quality of life. Therefore, biomarkers to identify patients who will experience adverse events would be very valuable in treatment planning.Materials and methodsBetween September 2016 and December 2019, patients scheduled for single-agent apatinib were prospectively enrolled and underwent ¹⁸F-RGD positron emission tomography/computed tomography (PET/CT) pre-treatment. Maximum and mean standard uptake values (SUV_max and SUV_mean) were obtained from thyroid, liver, gastric cardia, gastric body, gastric pylorus and spleen. Statistical methods included the independent sample t-test, Mann-Whitney U-test, receiver operating characteristic curve analysis and chi-squared test.ResultsIn total, 60 patients were initially screened and consented for ¹⁸F-RGD PET/CT scans. The three most frequent adverse events were fatigue (50%), hypertension (36%) and nausea (36%), accounting for 72% in the 50 patients included in the analysis. SUV_max and SUV_mean of thyroid and liver were significantly associated with fatigue, whereas SUV_max and SUV_mean of thyroid and spleen were significantly associated with hypertension and SUV_max and SUV_mean of thyroid and gastric cardia were significantly associated with nausea (all P < 0.05). The most significant predictors of adverse events were ¹⁸F-RGD SUV_max-liver for fatigue (area under the curve [AUC] = 0.682), SUV_max-spleen for hypertension (AUC = 0.688) and SUV_{max-gastric cardia} for nausea (AUC = 0.698). Classified by the cut-off values for SUV_max-liver (4.57), SUV_max-spleen (6.77) and SUV_{max-gastric cardia} (2.10), patients with low RGD SUV_max in liver, spleen and gastric cardia had statistically higher incidence of fatigue (67.9% versus 27.3%, P = 0.002), hypertension (55.6% versus 13.0%, P = 0.004) and nausea (61.1% versus 21.9%, P = 0.006).ConclusionsLow pre-treatment ¹⁸F-RGD uptake in the liver, spleen and gastric cardia were predictive of the adverse events fatigue, hypertension and nausea during apatinib treatment, respectively.     

Clinical significance of cachexia index in patients with hepatocellular carcinoma after hepatic resection

BackgroundCancer cachexia has been associated with unfavorable outcomes in several malignancies. The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been proposed as a novel biomarker of cachexia. Therefore, we here investigated prognostic value of the CXI in patients with hepatocellular carcinoma (HCC) after hepatic resection.MethodsThe study comprised 213 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. First, the skeletal muscle index (SMI) was calculated as the area of the psoas muscle at the third lumbar vertebra/(the height)². The CXI was then calculated by the following formula: SMI x serum albumin level/neutrophil-to-lymphocyte ratio (NLR). We retrospectively investigated the relationship between the CXI and disease-free survival as well as overall survival.ResultsIn multivariate analyses, female (p < 0.01), hepatitis B surface antigen-positivity (p < 0.01), preoperative serum alpha-fetoprotein level ≥20 ng/mL (p = 0.01), preoperative serum protein induced by vitamin K absence or antagonist-II level ≥200 mAU/mL (p = 0.02), multiple tumors (p < 0.01), macrovascular invasion (p = 0.04), type of resection (p < 0.01), and low CXI (p = 0.03) were significant predictors of disease-free survival, while Child-Pugh grade B (p < 0.01), poor tumor differentiation (p = 0.05), multiple tumors (p = 0.01), macrovascular invasion (p = 0.04), NLR (p = 0.04), and low CXI (p < 0.01) were significant predictors of overall survival. In the subgroup analysis of advanced T stage, the CXI was associated with both disease-free (p < 0.01) and overall survival (p = 0.06).ConclusionsThe CXI can be a prognostic indicator in patients with HCC after hepatic resection, suggesting the importance of comprehensive biomarker which includes skeletal muscle, inflammation, and nutritional status.     

Abdominal lymph node recurrence from colorectal cancer: Resection should be considered as a curative treatment in patients with controlled disease

BackgroundLymph node recurrences (LNR) from colorectal cancer (CRC) still represent a therapeutic challenge, as standardized recommendations have yet to be established. The aim of this study was to analyze short- and long-term oncological outcomes following resection of LNR from CRC.MethodsAll patients with previously resected CRC who underwent histopathologically confirmed LNR resection in 3 tertiary referral centers between 2010 and 2017 were reviewed. Short- and long-term outcomes were analyzed, mainly recurrence-free and overall survival. Further recurrences following LNR resection were also analyzed.ResultsOverall, 18 patients were included. Primary CRC was left-sided in 16 (89%) patients, staged T3-4 in 15 (83%), N+ in 14 (78%) and presented with synchronous metastases in 8 (43%). Median time interval between primary CRC and LNR resections was 31 months. Performed lymphadenectomies were aortocaval (n = 10), pelvic (n = 7), in hepatic pedicle (n = 3) and mesenteric (n = 1). Four patients had associated liver metastases resection. Three (17%) presented with postoperative complications, of which one Clavien-Dindo 3. Fourteen (78%) patients presented with further recurrences after a mean delay of 9 months, with 36% of patients presenting with early (<6 months) recurrence. Five (36%) patients could undergo secondary recurrence resection and 3 (21%) patients radiotherapy. Median overall survival following LNR resection reached 44 months.ConclusionsCurrent results suggest that LNR resection is feasible and associated with improved survival, in selected patients. Longer time interval between primary CRC resection and LNR occurrence appeared to be a favorable prognostic factor whereas multisite recurrence appeared to be associated with impaired long-term survival.     

Surgical and non-surgical complications after colorectal cancer surgery in older patients; time-trends and age-specific differences

BackgroundTrends of surgical and non-surgical complications among the old, older and oldest patients after colorectal cancer (CRC) surgery could help to identify the best target outcome to further improve postoperative outcome.Materials and methodsAll consecutive patients ≥70 years receiving curative elective CRC resection between 2011 and 2019 in The Netherlands were included. Baseline variables and postoperative complications were prospectively collected by the Dutch ColoRectal audit (DCRA). We assessed surgical and non-surgical complications over time and within age categories (70–74, 75–79 and ≥ 80 years) and determined the impact of age on the risk of both types of complications by using multivariate logistic regression analyses.ResultsOverall, 38648 patients with a median age of 76 years were included. Between 2011 and 2019 the proportion of ASA score ≥3 and laparoscopic surgery increased. Non-surgical complications significantly improved between 2011 (21.8%) and 2019 (17.1%) and surgical complications remained constant (from 17.6% to 16.8%). Surgical complications were stable over time for each age group. Non-surgical complications improved in the oldest two age groups. Increasing age was only associated with non-surgical complications (75–79 years; OR 1.17 (95% CI 1.10–1.25), ≥80 years; OR 1.46 (95% CI 1.37–1.55) compared to 70–74 years), not with surgical complications.ConclusionThe reduction of postoperative complications in the older CRC population was predominantly driven by a decrease in non-surgical complications. Moreover, increasing age was only associated with non-surgical complications and not with surgical complications. Future care developments should focus on non-surgical complications, especially in patients ≥75 years.     

Sarcopenia and primary tumor location influence patients outcome after liver resection for colorectal liver metastases

IntroductionRight-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. The prevalence of sarcopenia is known to worsen the outcome after hepatic resection. We sought to investigate the prevalence of sarcopenia and its prognostic application according to the primary CRC tumor site.Methods355 patients (62% male) who underwent liver resection in our center were identified. Clinicopathologic characteristics and long-term outcomes were stratified by sarcopenia and primary tumor location (right-sided vs. left-sided). Tumors in the coecum, right sided and transverse colon were defined as right-sided, tumors in the left colon and rectum were defined as left-sided. Sarcopenia was assessed using the skeletal muscle index (SMI) with a measurement of the skeletal muscle area at the level L3.ResultsPatients who underwent right sided colectomy (n = 233, 65%) showed a higher prevalence of sarcopenia (35.2% vs. 23.9%, p = 0.03). These patients also had higher chances for postoperative complications with Clavien Dindo >3 (OR 1.21 CI95% 0.9–1.81, p = 0.05) and higher odds for mortality related to CRC (HR 1.2 CI95% 0.8–1.8, p = 0.03).On multivariable analysis prevalence of sarcopenia remained independently associated with worse overall survival and disease free survival (overall survival: HR 1.47 CI 95% 1.03–2.46, p = 0.03; HR 1.74 CI95% 1.09–3.4, p = 0.05 respectively).ConclusionSarcopenia is known to have a worse prognosis in patients with CRLM and CRC. Depending on the primary location sarcopenia has a variable effect on the outcome after liver resection.     

Decreased Muscle Mass Prior to and Following Chemotherapy Predicts Morbidity in Testicular Cancer Patients Undergoing Post-Chemotherapy Retroperitoneal Lymph Node Dissection

Introduction/BackgroundThe importance of nutritional status before oncologic surgery has been demonstrated in several solid malignancies. Testicular cancer primarily effects young men, and therefore clinicians may not consider sarcopenia as a factor in this population. We therefore sought to determine the impact of decreased muscle mass, measured by psoas muscle diameter, on outcomes in patients undergoing post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) for metastatic germ cell tumors (mGCTs).Materials and MethodsRecords of all patients undergoing PC-RPLND for mGCTs at our institution were reviewed. Muscle mass was assessed by measuring cross-sectional area of the psoas muscle on pre-chemotherapy and pre-operative computerized tomography. Psoas Index (PSI) was calculated by adjusting total psoas area for patient height (cm²/m²). Univariate and multivariate analysis was performed to assess the predictive value of sarcopenia for morbidity and mortality following PC-RPLND.ResultsFrom 2014-2019, 95 patients underwent PC-RPLND, of whom 64 patients had both pre-chemo and pre-operative cross-sectional imaging. Prior to chemotherapy, mean PSI was 7.36 cm²/m², which decreased to 7.06 cm²/m² (P = .041) following chemotherapy. Patients with Stage III disease had a lower mean PSI than patients with Stage I disease (6.84 cm²/m² vs 7.46 cm²/m², P = .047). Patients who suffered post-operative complications had a lower mean PSI (6.39 cm²/m² vs 7.37 cm²/m², P = .020).ConclusionDecreased muscle mass was predictive of morbidity in patients undergoing PC-RPLND. Patients with higher disease burden had lower pre-operative muscle mass. Further assessment of pre-operative nutritional status in this population may reduce morbidity following PC-RPLND.     

Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC – Is it the exception to the rule?

BackgroundAlthough primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC.MethodsAll eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence–free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS.ResultsA total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98).ConclusionsIn contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.     

Disease and Clinical Characteristics of Patients With a Clinical Diagnosis of Myelofibrosis Enrolled in the MOST Study

BackgroundClinical characteristics and treatment patterns of patients with lower-risk myelofibrosis (MF) are not well described. This analysis from the MOST (NCT02953704) assessed the demographic and clinical characteristics and treatment patterns of patients with the clinical diagnosis of lower-risk MF at enrollment.Patients and MethodsMOST is an ongoing, prospective, observational study in patients with clinical diagnoses of MF or essential thrombocythemia enrolled at clinical practices throughout the United States. Patients included in the MF cohort (≥18 years of age) had low-risk MF by the Dynamic International Prognostic Scoring System or intermediate-1 (INT-1) risk MF (by age >65 years only) at enrollment. Patient data were entered into an electronic case report form during usual-care visits over a planned 36 month observation period.ResultsTwo hundred five patients were eligible for this analysis (low risk, n = 85; INT-1 risk, n = 120; median age, 68 years [range, 35–88]); 166 patients (81.0%) had mutation testing results available. The median time from MF diagnosis to enrollment was 1.8 years. Hemoglobin and hematocrit levels were below the normal range in 50.5% and 48.7% of patients, respectively. Nearly all (98.0%) patients had comorbid conditions, most commonly hypertension (49.8%). Fatigue was the most common physician-reported MF symptom (30.7%). At enrollment, 55.6% of patients were receiving MF-directed monotherapy, most frequently hydroxyurea (46.5%) or ruxolitinib (40.4%).ConclusionFuture longitudinal analyses of data from MOST will help identify unmet needs and characterize how patients with lower-risk MF are managed throughout the disease course.     

Preoperative hiatal hernia in esophageal adenocarcinoma; does it have an impact on patient outcomes?

BackgroundThe impact of hiatal hernia (HH) on oncologic outcomes of patients with esophageal adenocarcinoma (AC) remains unclear. The aim of this study was to assess the effect of pre-existing HH (≥3 cm) on histologic response after neoadjuvant treatment (NAT), overall (OS) and disease-free survival (DFS).MethodsAll consecutive patients with oncological esophagectomy for AC from 2012 to 2018 in our center were eligible for assessment. Categorical variables were compared with the X² or Fisher's test, continuous ones with the Mann-Whitney-U test, and survival with the Kaplan-Meier and log-rank test.ResultsOverall, 101 patients were included; 33 (32.7%) had a pre-existing HH. There were no baseline differences between HH and non-HH patients. NAT was used in 81.8% HH and 80.9% non-HH patients (p = 0.910), most often chemoradiation (63.6% and 57.4% respectively, p = 0.423). Good response to NAT (TRG 1–2) was observed in 36.4% of HH versus 32.4% of non-HH patients (p = 0.297), whereas R0 resection was achieved in 90.9% versus 94.1% respectively (p = 0.551). Three-year OS was comparable for the two groups (52.4% in HH, 56.5% in non-HH patients, p = 0.765), as was 3-year DFS (32.7% for HH versus 45.6% for non-HH patients, p = 0.283).ConclusionHH ≥ 3 cm are common in patients with esophageal AC, concerning 32.7% of all patients in this series. However, its presence was neither associated with more advanced disease upon diagnosis, worse response to NAT, nor overall and disease-free survival. Therefore, such HH should not be considered as risk factor that negatively affects oncological outcome after multimodal treatment of esophageal AC.     

Perioperative nutritional assessment and interventions in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): A systematic review

BackgroundPeritoneal carcinomatosis is a catabolic state and cytoreductive surgery (CRS) is a high morbidity operation. Optimising perioperative nutrition is crucial to improve outcomes. This systematic review sought to examine literature describing clinical outcomes related to preoperative nutrition status and nutrition interventions in patients undergoing CRS with hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA systematic review was registered with PROSPERO (300326). A search of eight electronic databases was undertaken on 8th May 2022 and reported according to the PRISMA statement. Studies reporting nutrition status through use of screening and assessment tools, nutrition interventions or nutrition-related clinical outcomes for patients undergoing CRS with HIPEC were included.ResultsOf 276 screened studies, 25 studies were included for review. Commonly used nutrition assessment tools for CRS-HIPEC patients included Subjective Global Assessment (SGA), sarcopenia assessment with computed tomography, preoperative albumin, and body mass index (BMI). Three retrospective studies compared SGA with postoperative outcomes. Malnourished patients were more likely to have postoperative infectious complications (p = 0.042 SGA-B, p = 0.025 SGA-C). Malnutrition was significantly associated with increased hospital length of stay (LOS) in two studies (p = 0.006, p = 0.02), and with overall survival in another study (p = 0.006). Eight studies analysing preoperative albumin levels reported conflicting associations with postoperative outcomes. BMI in five studies was not associated with morbidity. One study did not support routine nasogastric tube (NGT) feeding.ConclusionsPreoperative nutritional assessment tools, including SGA and objective sarcopaenia measures, have a role in predicting nutritional status for CRS-HIPEC patients. Optimisation of nutrition is important for preventing complications.     

Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic

BackgroundBrain metastases are frequent complications in patients with non-small-cell lung cancer (NSCLC) associated with significant morbidity and poor prognosis. Our goal is to give a global overlook on clinical efficacy from immune checkpoint inhibitors in this setting and to review the role of biomarkers and molecular interactions in brain metastases from patients with NSCLC.MethodsWe reviewed clinical trials reporting clinical outcomes of patients with NSCLC with brain metastases as well as publications assessing the tumor microenvironment and the complex molecular interactions of tumor cells with immune and resident cells in brain metastases from NSCLC biopsies or preclinical models.ResultsAlthough limited data are available on immunotherapy in patients with brain metastases, immune checkpoint inhibitors alone or in combination with chemotherapy have shown promising intracranial efficacy and safety results. The underlying mechanism of action of immune checkpoint inhibitors in the brain niche and their influence on tumor microenvironment are still not known. Lower PD-L1 expression and less T CD8⁺ infiltration were found in brain metastases compared with matched NSCLC primary tumors, suggesting an immunosuppressive microenvironment in the brain. Reactive astrocytes and tumor associated macrophages are paramount in NSCLC brain metastases and play a role in promoting tumor progression and immune evasion.ConclusionsDiscordances in the immune profile between primary tumours and brain metastases underscore differences in the tumour microenvironment and immune system interactions within the lung and brain niche. The characterization of immune phenotype of brain metastases and dissecting the interplay among immune cells and resident stromal cells along with cancer cells is crucial to unravel effective immunotherapeutic approaches in patients with NSCLC and brain metastases.     

Systemic Chemotherapy With or Without Hepatic Arterial Infusion Chemotherapy for Liver Metastases From Pancreatic Cancer: A Propensity Score Matching Analysis

BackgroundThe significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM.Patient and MethodsThe PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed.ResultsThe main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor.ConclusionOur findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.     

Association of Apatinib and Breast Cancer: A systematic review and meta-analysis

BackgroundBreast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known. Therefore, this meta-analysis was performed to assess the efficacy and safety of apatinib in the treatment of BC.MethodsStudies comparing the effects of apatinib-based therapy versus control among BC patients were included. On January 21, 2022, a systematic search was performed in 9 databases. The risk ratio (RR) with 95% confidence interval (CI) was used to estimate efficacy and safety. The I square value (I²) was used to assess heterogeneity. A leave-one-out sensitivity analysis was also conducted. Publication bias was assessed by funnel plots and Egger's and Begg's tests.ResultsA total of 31 studies including 2,258 BC patients were included. The results showed that apatinib group had a significant improvement in disease control rate (DCR, RR = 1.43, 95% CI = 1.35–1.52, I² = 43.8%) and objective response rate (ORR, RR = 1.79, 95% CI = 1.51–2.13, I² = 61.8%) compared to the control group. Except for hemorrhage, hypertension, and hand-foot syndrome, the adverse events were similar between apatinib group and control group. Subgroup analyses found statistically significant differences in DCR in all subgroups except for apatinib combined with radiation therapy and with paclitaxel liposome plus S1. For ORR, there were statistically significant differences in all subgroups except for the radiation therapy, and apatinib monotherapy subgroups.ConclusionsOur study shown apatinib showed good efficacy and acceptable safety in the treatment of BC patients. More high-quality randomized controlled trials from different regions and countries are needed to confirm our findings.     

Prognostic significance of CA-125 re-elevation after interval debulking surgery in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy

AimsWe evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC).MethodsThe data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL.ResultsAmong 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98).ConclusionAmong patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.     

The Cardioprotective Effect of Vitamin D in Breast Cancer Patients Receiving Adjuvant Doxorubicin Based Chemotherapy

PurposeThe primary objective of this study was to investigate the potential protective effect of Vitamin D (Vit D) on DOX induced cardio toxicity (DIC) in early breast cancer patients receiving adjuvant DOX based chemotherapy (AC). The secondary objective was to investigate the anti–inflammatory effect of Vit D by measuring serum IL-6 and its correlation with cardio toxicity.MethodsThis study was carried out on 150 newly diagnosed women with breast cancer who were planned to receive four cycles of adjuvant AC chemotherapy regimen (60 mg/m² DOX and 600 mg/m² cyclophosphamide) every 21 days. Study patients were randomized 1:1 into a control group treated with AC and a Vit D group treated with AC plus 0.5 µg of Vit D (Bon One 0.5 µg) orally once daily during the whole treatment course. The cardio protective effect of Vit D was assessed by measuring serum levels of Lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and anti–inflammatory Interleukin 6 (IL-6) at baseline, and after 4 cycles of AC in all study patients.ResultsVit D supplementation in Vit D group patients was associated with a significant decrease (P < 0.001) in serum levels of LDH, cTnT, and IL-6 compared to the control group .ConclusionThe present work provides a promising clinical evidence to support the cardio protective effects of Vit D against DIC through attenuating the evoked pro-inflammatory cytokines induced by DOX.     

Impact of TP53 Mutations on EGFR-Tyrosine Kinase Inhibitor Efficacy and Potential Treatment Strategy

BackgroundWe investigated the impact of factors that influence TP53 mutations on the efficacy of EGFR-tyrosine kinase inhibitors and potential treatment strategies.Materials and MethodsTumor samples were collected to screen gene mutations by next-generation sequencing, as well as the patients’ baseline characteristics. The overall response to treatment with TKIs was evaluated based on interval computed tomography scans at each follow-up time point. A Fisher's exact test and log-rank test were used to determine the statistical differences in this study.ResultsA total of 1134 clinical samples were collected from NSCLC patients, and TP53^mut was identified in 644 cases and EGFR^mut in 622 cases. A low frequency of TP53^mut or more than 50% EGFR co-mutation rate were related to the prognosis of TKI-treated patients. In addition, TP53^mut in the region outside of the DB domain had the strongest correlation with TKI resistance, whereas various types of mutations in the DB domain only had an impact on PFS. A grouping study of EGFR-TKI-based treatment revealed that EGFR-TKIs with chemotherapy were associated with more significant survival benefits for patients with prognostic TP53^mut, whereas EGFR-TKI therapy was favorable for TP53^wt patients. Furthermore, TP53^mut could shorten the time to the relapse of postoperative patients, who will also likely respond well to EGFR-TKIs with chemotherapy.ConclusionVarious characteristics of TP53^mut affect the prognosis of TKI-treated patients to varying degrees. EGFR-TKIs with chemotherapy were benefit for patients’ survival with prognostic TP53^mut, which provides an important reference for treatment management of EGFR^mut patients.