Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

Immune checkpoint inhibitor-related hearing loss: a systematic review and analysis of individual patient data.

PURPOSE: Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies. METHODS: We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were "hearing loss" OR "hearing impairment" OR "ototoxicity" OR "vestibular toxicity" OR "audiovestibular toxicity" AND "immune checkpoint inhibitor" OR "immunotherapy." RESULTS: A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively. CONCLUSION: We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.

Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

The risk of malnutrition and its clinical implications in older patients with cancer.

AIM: Malnutrition is a common geriatric syndrome with multiple negative outcomes including mortality. However, there is a scarcity of literature that focuses on the relationship between malnutrition risk and its clinical implications on geriatric syndromes and mortality among cancer patients. The aim of this study is to determine the clinical importance of malnutrition risk in geriatric oncology practice. METHOD: 180 patients with cancer who were ≥ 65 years were included in the study. All patients were questioned in terms of geriatric syndromes, including polypharmacy, frailty, probable sarcopenia, fall risk, dynapenia, depression, cognitive impairment, insomnia, and excessive daytime sleepiness. Mini Nutritional Assessment scores > 23.5 and 17-23.5 were categorized as well-nourished and malnutrition risk, respectively. RESULTS: Of the 180 patients (mean age 73.0 ± 5.6 years, female: 50%), the prevalence of malnutrition risk was 28.9%. There was no statistically significant difference between the groups in terms of age, gender, education, marital status, body mass index, and comorbidities except for chronic obstructive pulmonary disease (p > 0.05). After adjustment for age, sex, and body mass index; polypharmacy (odds ratio [OR]: 3.17; 95% confidence interval [CI], 1.48-6.81), reduced calf circumference (OR: 3.72; 95% CI, 1.22-11.38), fall risk (OR: 2.72; 95% CI, 1.03-7.23), depression (OR: 6.24; 95% CI, 2.75-14.18), insomnia (OR: 4.89; 95% CI, 2.16-11.05), and frailty (OR: 2.44; 95% CI, 1.75-3.40) were associated with malnutrition risk compared to well-nourished patients (p < 0.05). Median survival in patients with malnutrition risk was 21.3 months (range 14.1-28.4 95% CI) and median survival in patients who were defined as well nourished was not reached (p < 0.001). CONCLUSION: The risk of malnutrition was associated with a higher risk for all-cause mortality in older patients with cancer, and was associated with many geriatric syndromes, including polypharmacy, fall risk, frailty, insomnia, and depression.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Impact of coronaphobia on treatment and follow-up compliance of cancer patients.

The aim of this study was to assess the impact of coronaphobia on treatment and follow-up compliance in cancer patients. The records of 230 cancer patients were reviewed. Coronaphobia was assessed via the validated COVID-19 Phobia Scale (C19P-S). A total of 64% of the patients had a high coronaphobia score. Among them, 59% were noncompliant. In multivariate logistic regression analysis, low educational status, treatment type, following COVID-19 news, having knowledge about COVID-19 transmission and higher C19P-S score were associated with noncompliance (p = 0.006, p < 0.001, p = 0.002, p = 0.002 and p = 0.001, respectively). Multivariate analysis revealed that having knowledge about COVID-19 transmission was related to a higher C19P-S score (p = 0.001). The cancer patients studied had significant coronaphobia. Moreover, greater coronaphobia was significantly associated with noncompliance with follow-up and treatment.

Assessment of abuse and related factors in older patients with cancer.

BACKGROUND: Older cancer patients are more likely to present with functional dependency, multiple comorbidities, polypharmacy, malnutrition, and cognitive dysfunction than their younger counterparts which increases the risk of elder abuse. Herein, in this single-institution observational study, we aimed to determine the frequency and risk factors of abuse in cancer patients aged 70 and above. METHODS: A total of 217 cancer patients aged ≥ 70 years who applied to the medical oncology outpatient clinic between June 2020 and January 2021 were included in this study. Informed consent was obtained before data collection. The Hwalek-Sengstock Elder Abuse Screening Test (H-S/EAST) was used to evaluate elder abuse. Sociodemographic characteristics and clinical measurements were collected. RESULTS: The mean age was 75.5, and 59.4% were male. The prevalence of abuse risk in older patients with cancer was 39.2%. In the multivariate logistic regression model, applying to the outpatient clinic for treatment (OR: 3.369, 95% CI: 1.455-7.802, p = 0.005), living in urban (OR: 5.787, 95% CI: 2.377-14.090, p < 0.001), history of falls (OR: 4.587, 95% CI: 1.789-11.762, p = 0.002), and being depressed according to the Geriatric Depression Scale-15 (GDS-15) score (OR: 10.788, 95% CI: 4.491-25.914, p < 0.001) were associated with an increased risk of elder abuse. Primary/junior education level and high school/university education level were protective against elder abuse risk compared to being illiterate (OR: 0.073, 95% CI: 0.025-0.210 and OR: 0.213, 95% CI: 0.056-0.806, respectively). CONCLUSION: Cancer patients aged ≥ 70 years had a high risk of elder abuse. Elder abuse should be screened in patients with cancer, and the effects of this phenomenon on cancer care should be investigated in larger studies.

Effects of adenosine triphosphate on vandetanib induced skin damage in rats.

PURPOSE: Vandetanib is a wide spectrum tyrosine kinase inhibitor used for the treatment of metastatic medullary thyroid cancer (MTC) and various other cancer types. Although it is usually well-tolerated it has been linked to a variety of severe dermatologic reactions. Our study aimed was to investigate adenosine 5'-triphosphate (ATP) on vandetanib-induced skin damage. MATERIALS AND METHODS: A total number of 18 rats were divided into three equal groups as vandetanib group (VDB), vandetanib plus ATP group (VAT), and healthy group (HG); 25 mg/kg ATP was injected intraperitoneally (ip) to the VAT group. Normal saline was given to the HG and VDB groups as solvent via intraperitoneally. One hour later, 25 mg/kg vandetanib was applied orally via an orogastric catheter in the VAT and VDB groups. This procedure was repeated once daily for 4 weeks. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS) levels in rats' skin tissues were evaluated with histopathological analyses. RESULTS: MDA and TOS levels measured higher in the VDB group compared to the VAT and HG groups (p < 0.001). tGSH and TAS levels of the VDB group measured lower than the VAT and HG groups (p < 0.001). The structure and morphology of skin tissue were normal in the control group. In the VDB group, skin tissue damage with thinner epitelium, ruptured and degenerated hair follicles, abnormal accumulation of abnormal keratin on the epithelium and oedematous areas in the dermis was observed. In the VAT group, these findings were significantly improved. CONCLUSION: We demonstrated that adenosine triphosphate can prevent vandetanib-induced skin toxicity in rats for the first time. The promising results denote that further studies testing this agent in other animal models and in humans are warranted.

Geriatric nutritional risk index and controller nutritional status score before metastatic first-line chemotherapy predict survival in patients over 70 years of age with metastatic bladder cancer.

Introduction: Several prognostic factors have been identified in patients with metastatic bladder cancer (BC). As it is known, older adult patients are prone to nutritional deficiency. The knowledge about nutrition and impact on survival in older patients with metastatic bladder cancer is missing. It is necessary to specifically examine this population. Because timely interventions can make a positive impact on this patients population. This retrospective study aimed to evaluate the prognostic effect of the Geriatric Nutritional Risk Index (GNRI), Controller Nutritional Status (CONUT) score and Prognostic Nutritional Index (PNI) before first-line chemotherapy in the metastatic stage in patients with metastatic bladder cancer over 70. Participants and methods: Patients over 70 with pathologically confirmed denovo metastatic or recurrent metastatic bladder cancer were included in the study. Patients with infections diagnosed at the time of diagnosis, autoimmune diseases or history of steroid use were excluded. Since our population consists of a specific age group with a specific cancer, we found a new cut-off value by performing ROC analysis to ensure optimal sensitivity and specificity in terms of progression. Low GNRI value was related with poor nutritional status. Low PNI value was related with poor nutritional status and high CONUT score was related with poor nutritional status. Factors predicting overall survival (OS) and Progression-Free Survival (PFS) were assessed using both univariate and multivariate Cox proportional hazards analyses. Results: 106 patients were included in the study and the average age was 75.5 years. In the GNRI-Low group, PFS was significantly shorter than that in the GNRI-High group [HR (95% CI) = 57.1 (12.8-255.5), (p < 0.001)]. Among those with a low-CONUT score, PFS was found to be longer than that in the high-CONUT group [HR (95% CI) = 1.7 (1.0-3.0), (p = 0.039)]. The median PFS of the PNI-Low group wasn't significantly shorter than that of the PNI-High group [HR (95% CI) = 1.8 (0.5-6.2), (p = 0.359)]. Conclusion: Our study suggests that the GNRI and CONUT scores are useful for predicting survival in patients over 70 years of age with BC.

Malnutrition and Related Factors in Older Patients With Gastrointestinal Cancer Receiving Chemotherapy.

Objectives The incidence and mortality of gastrointestinal (GI) malignancies increase exponentially with age. Malnutrition is a documented poor prognostic factor in older patients with cancer. There is insufficient data about the prevalence of malnutrition and associated factors in older patients with GI cancer. Thus, we aimed to investigate the prevalence of malnutrition and related factors among older patients with GI cancer. Methods A total of 121 patients aged over 70 years diagnosed with various types of GI cancers applied to the medical oncology clinic included in this cross-sectional study. We evaluated the nutrition status with a mini-nutritional assessment (MNA) score. Results The prevalence of malnutrition was 76 (62.8%) in our study population. The mean age was 76.5 (range 70 to 90 years), and 71 (58.6%) were male. In the multivariate logistic regression model, lower BMI (OR: 3.379, 95% CI: 1.465-7.812, p = 0.005), having gastroesophageal cancer (OR: 5.797, 95% CI: 2.387-14.091, p<0.001), treating with palliative chemotherapy (OR: 4.597, 95% CI: 1.799-11.772, p = 0.002), and frailty according to G8 score (OR: 10.798, 95% CI: 4.495-25.924, p<0.001) were associated with malnutrition. Conclusions Our study revealed that palliative chemotherapy, low BMI, frailty, and gastroesophageal cancer are risk factors for malnutrition in older patients with GI cancer. Physicians need to be aware of patients who may be at risk for malnutrition. Patients at risk of malnutrition may benefit from interventions to enhance their nutrition. Further studies consisting of larger cohorts are needed to determine malnutrition and related factors in older patients with cancer.

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

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

Comparison of HER2-zero and HER2-low in terms of clinicopathological factors and survival in early-stage breast cancer: A systematic review and meta-analysis.

BACKGROUND: The prognostic differences between HER2-zero and HER2-low breast cancer (BC) remain unclear. Purpose of this meta-analysis is to investigate the differences between HER2-low and HER2-zero in terms of clinicopathological factors and survival outcomes in early-stage BC. METHODS: We searched major databases and congress proceedings until November 1, 2022 to identify studies comparing HER2-zero and HER2-low in early-stage BC. HER2-zero immunohistochemically (IHC) was defined as score 0, while HER2-low was defined as IHC 1+ or 2+/in situ hybridization negative. RESULT: A total of 23 retrospective studies involving 636,535 patients were included. HER2-low rate was 67.5% in the hormone receptor (HR)-positive group, while this rate was 48.6% in the HR-negative group. In the analysis of clinicopathological factors by HR status, the proportion of premenopausal patients within the HR-positive group was greater in the HER2-zero arm (66.5% vs 61.8%), whereas grade 3 tumors (74.2% vs 71.5%), patients younger than 50 years of age (47.3% vs 39.6%), and T3-T4 tumors (7.7% vs 6.3%) within the HR-negative group was higher in the HER2-zero arm. In both the HR-positive and HR-negative groups, the HER2-low arm showed significantly improved results for disease-free survival (DFS) and overall survival (OS). The hazard ratios for DFS and OS in the HR-positive group were 0.88 (95% CI 0.83-0.94) and 0.87 (95% CI 0.78-0.96), respectively. In the HR-negative group, the hazard ratios for DFS and OS were 0.87 (95% CI 0.79-0.97) and 0.86 (95% CI 0.84-0.89), respectively. CONCLUSION: In early-stage BC, HER2-low is associated with better DFS and OS compared to HER2-zero, regardless of HR status.

Efficacy and safety of concomitant chemo-endocrine therapy in neoadjuvant treatment of hormone-positive HER2-negative breast cancer: a systemic review and meta-analysis.

BACKGROUND: The rate of pathological complete response (pCR) with both chemotherapy alone (CT) and endocrine therapy (ET) in the neoadjuvant (Na) treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) is unsatisfactory. Limited data on neoadjuvant concomitant chemotherapy and endocrine therapy (NaCET) are available. RESEARCH DESIGN AND METHODS: In this meta-analysis analyzed the efficacy and safety of randomized controlled trials (RCT) comparing the use of NaCET in HR-positive/HER2-negative BC. A comprehensive search was performed on PubMed, Cochrane Library and EMBASE databases, and congress paper lists for studies published/presented until 1 December 2022. RESULTS: Five RCTs involving a total of 630 patients were included. A pooled analysis of the five studies demonstrated that the pCR ratio was numerically higher in the NaCET arm than in the NaCT arm, but the difference was not statistically significant (6.5% vs. 3.8%; OR:1.72, 95% CI 0.82-3.62). Nonetheless, the NaCET arm exhibited a significantly higher objective response rate (ORR) (82% vs. 72.7%; OR:1.77, 95% CI 1.20-2.62). There was no difference between the arms in terms of grade 3-5 adverse events. CONCLUSIONS: In HR-positive/HER2-negative BC, NaCET significantly increases ORR without an increase in serious adverse events. Although the pCR rate increased numerically, it was not statistically significant.

Dynamic changes in systemic immune-inflammation index predict pathological tumor response and overall survival in patients with gastric or gastroesophageal junction cancer receiving neoadjuvant chemotherapy.

AIM: Systemic inflammation has been associated with chemoresistance and prognosis in solid tumors. Systemic immune-inflammation index (SII) is a novel marker derived from complete blood count. We investigated whether differences between SIIs measured before and after neoadjuvant chemotherapy (NACT) are associated with tumor regression grade (TRG) and survival in gastric and gastroesophageal junction (GEJ) cancer patients. METHODS: Records of gastric and GEJ cancer patients treated with NACT in two centers were evaluated retrospectively. Patients were categorized according to difference between pre- and post-NACT SII values (ΔSII). Association between clinicopathological factors and TRG was analyzed using logistic regression method. Predictors of disease-free and overall survival (DFS and OS) were determined with Cox regression models. RESULTS: The study included 140 patients. Patients with ΔSII<0 were more likely to achieve TRG 0/1 (45.2% vs. 19.1%, p = 0.003) and ΔSII<0 was an independent predictor of TRG 0/1 (OR = 6.05, p<0.001). DFS and OS of patients with ΔSII<0 were also significantly longer (p = 0.031 and p = 0.006, respectively). After adjustment for other variables, ΔSII≥0 was an independent prognostic factor for OS (Hazard ratio (HR) = 2.13, p = 0.008). CONCLUSIONS: Changes in SII, which is a low-cost and easily accessible marker, may be used to estimate prognosis, individualize postoperative treatment and optimize surveillance in gastric and GEJ cancer patients treated with NACT.

The Effect of HER2-Low Status on Pathological Complete Response and Survival in Triple-Negative Breast Cancer: A Systemic Review and Meta-Analysis.

This meta-analysis conducted a comprehensive analysis of research investigating the correlation between HER2 expression levels and treatment outcomes in early-stage triple-negative breast cancer (TNBC) patients. We systematically searched major databases for studies published up to January 01, 2023. The data from various studies examined the relationship between HER2-zero and HER2-low tumors in terms of pathological complete response (pCR) rates, disease-free survival (DFS), and overall survival (OS) outcomes. The odds ratio (OR) and 95% confidence interval (CI) by the number of events were calculated using the Mantel-Haenszel method to analyze pCR. The hazard ratio and 95% CI were calculated using the inverse variance method for DFS and OS. In all comparisons, I2 was 0% and no heterogeneity was detected. A total of 12 retrospective studies involving 4094 patients were included. Thirty-six percent of the patients were in the HER2-low group. All 12 studies were included in the pooled analysis for pCR, and there was no difference between HER2-zero and HER2-low (40% vs. 38%, respectively; pooled OR:1.01 95% CI 0.88-1.16; I2: 0%). Four studies were included in the pooled analysis for DFS and 3 in the OS analysis. DFS and OS were significantly better in the HER2-low group (pooled hazard ratio: 0.67 for DFS, 0.64 for OS). There was no difference between HER2-low and HER2-zero in terms of pCR in early-stage TNBC. However, HER2-low was found to be associated with prolonged DFS and OS. PROSPERO REGISTRATION NUMBER: CRD42023391002.

Adoptive Cell Therapy in Hepatocellular Carcinoma: A Review of Clinical Trials.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Immune checkpoint inhibitors (ICIs) have become the new reference standard in first-line HCC treatment, replacing tyrosine kinase inhibitors (TKIs) such as sorafenib. Many clinical trials with different combinations are already in development to validate novel immunotherapies for the treatment of patients with HCC. Adoptive cell therapy (ACT), also known as cellular immunotherapy, with chimeric antigen receptors (CAR) or gene-modified T cells expressing novel T cell receptors (TCR) may represent a promising alternative approach to modify the immune system to recognize tumor cells with better clinical outcomes. In this review, we briefly discuss the overview of ACT as a promising treatment modality in HCC, along with recent updates of ongoing clinical trials.

Association of Serum Hepatocyte Growth Factor Level with Systemic Inflammatory Biomarkers in Patients with Pancreatobiliary Cancer.

BACKGROUND: Hepatocyte growth factor is a cytokine secreted by the stromal cells in the tumor microenvironment. There is little information about the clinical significance of serum hepatocyte growth factor level in patients diagnosed with pancreatobiliary cancer. The objective of the current study was to investigate the relationship between serum hepatocyte growth factor level with inflammation markers and the clinical features of patients with pancreatobiliary cancer. METHODS: A total of 62 patients with pancreatobiliary cancer were included in this study. Serum hepatocyte growth factor concentrations were evaluated utilizing the enzyme-linked immunosorbent assay method. RESULTS: The median serum hepatocyte growth factor level was 329.1 ng/mL (1.4-1051.1). The patients were categorized into 2 groups as those below the median hepatocyte growth factor level (low hepatocyte growth factor) and those above the median hepatocyte growth factor level (high hepatocyte growth factor). While 40.9% of the patients without metastasis were observed to be in the high hepatocyte growth factor group, 72.2% of the metastatic patients were observed to be in the high hepatocyte growth factor group (P = .025). The median levels of monocyte, monocyte-to-lymphocyte ratio, C-reactive protein, and C-reactive protein-to-albumin ratio were found to be significantly higher in the high hepatocyte growth factor group as compared to the low hepatocyte growth factor group (P < .050). CONCLUSION: The significant relationship between serum hepatocyte growth factor level and systemic inflammation markers in patients with pancreatobiliary cancer is shown for the first time in our study. This study, which showed a significant relationship between the presence of metastasis and serum hepatocyte growth factor level, suggests that serum hepatocyte growth factor level may be a prognostic biomarker in patients who are diagnosed with pancreatobiliary cancer.