The emerging predictive and prognostic role of HER2 in HER2-negative early breast cancer: a retrospective study.

PURPOSE: Many patients with early breast cancer (eBC) undergoing neoadjuvant chemotherapy do not achieve pathological complete response (pCR), which is a prognostic factor. We examined the role of HER2-low expression in predicting pCR and prognosis in HER2-negative eBC. METHODS: We evaluated patients with stage I-III HER2-negative BC, treated between 2013 and 2023 at The Royal Marsden NHS Foundation Trust, London. Tumors were classified based on estrogen receptor (ER) status and into HER2-low and HER2-zero subgroups. We analyzed pCR rates, relapse-free survival (RFS) and overall survival (OS). RESULTS: 754 patients were included in the analysis. pCR rate was 8.9% in the ER+ /HER2-low, 16.5% in the ER+ /HER2-zero, 38.9% in the ER- ER-/HER2-low and 35.9% in the ER-/HER2-zero eBC (p < 0.001). Multivariable analysis showed a significantly lower pCR rate in HER2-low compared to HER2-zero BC in the ER+ subgroup. At a median follow-up of 63.8 months (59.9-67.4), we observed longer OS in HER2-low compared to HER2-zero patients in the overall and in the ER+ population. There was no predictive or prognostic impact of HER2-low status in the ER- population. CONCLUSION: This study supports the interpretation of HER2 status as a possible prognostic and predictive biomarker for HER2-negative eBC, especially among patients with ER+ disease.

Post-Treatment Change in mir92a Levels Predicts AML Prognosis Better than Single Baseline or Post-Treatment Values.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous malignant disorder. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. METHODS: The study included 44 adult AML patients diagnosed according the WHO classification criteria. Circulating levels of mir92a were measured at baseline and on the 28th day after induction of treatment. Levels were classified as high (≥ median) or low (< median) expression. Change of mir92a levels was calculated by subtracting the baseline result from the post-treatment result. The study outcomes included achievement of complete remission (CR) at 28 days post-induction, progression free survival (PFS), and overall survival (OS). RESULTS: Patients with increased mir92a levels had significantly higher CR rate. They also had significantly lower mortality rate (3.7% versus 88.2%, p < 0.001), longer PFS time, and longer OS time. Cox-hazard regression analysis identified female gender and increased mir92a levels as independent predictors of PFS while only increased mir92a levels were identified as independent predictor of OS. CONCLUSIONS: Post-treatment change in levels of circulating mir92a can provide better prediction of PFS and OS in AML patients.

Impact of Center Volume on Cardiopulmonary and Mortality Outcomes after Immune-Checkpoint Inhibitors for Cancer: A Systematic Review and Meta-Analysis.

Immune-checkpoint inhibitors (ICIs) were proven effective in inducing tumor regression. However, its toxicity tends to be fatal. We sought to investigate the hospital volume/outcomes relationship. Databases were searched for studies reporting immune-checkpoint inhibitors adverse events (AEs) in patients with solid-organ malignancies. The outcomes were A) the pooled events rate (PER) of grade 5, grade 3-4, cardiac-related, and pulmonary-related AEs, and B) the assessment of the volume/outcomes relationship. One hundred and forty-seven studies met our inclusion criteria. The PER of grade 5, grade 3-4, and any-grade AEs was 2.75% (95%CI: 2.18-3.47), 26.69% (95%CI: 21.60-32.48), and 77.80% (95%CI: 70.91-83.44), respectively. The PER of pulmonary-related AEs was 4.56% (95%CI: 3.76-5.53). A higher number of annual cases per center was significantly associated with reduced grade 5 (p = 0.019), grade 3-4 (p = 0.004), and cardiac-related AEs (p = 0.035) in the meta-regression. In the current era of cancer immunotherapy, knowledge regarding the early diagnosis and management of immunotherapy-related AEs is essential. Our meta-analysis demonstrates the importance of center volume in improving outcomes and reducing the incidence of severe AEs.

The impact of hepatitis B virus and hepatitis C virus infections in patients with Hodgkin's and non-Hodgkin's lymphoma.

BACKGROUND: This study aimed to determine the prevalence of HCV and occult HBV among newly diagnosed pre-treatment Egyptian lymphoma patients and evaluate patients' outcomes based on the presence of the viral infections. METHODS: The study included 80 therapy-naïve lymphoma patients including 71 non-Hodgkin lymphoma (NHL) and 9 Hodgkin lymphoma disease (HD) in addition to 100 healthy volunteers. HBV screening using HBsAg and anti-HBc IgM and HCV using AB/Ag ELISA and real-time RT-PCR were screened in tested and control groups. The diagnosis was confirmed by histopathology. Overall survival (OS) and progression-free survival (PFS) were conducted to diseased patients. RESULTS: Healthy patients showed 4/100, (4%) active HCV infection and 1/100, (1%) active HBV infection and no occult HBV infection. Among NHL patients, 28 were positive for HBV (6 active and 22 occult HBV infection). Occult HBV was also detected in 5/9 HD patients. HCV was detected in (30/71, 42.3%) of NHL patients and in a single HD patient. Ten occult HBV NHL patients showed a mixed infection with HCV. The incidence of both HCV and HBV are higher in NHL than HL patients. After antitumor treatment, complete remission for lymphoma was achieved in 45% of patients. Both overall survival (OS) and progression-free survival (PFS) were correlated and significantly associated with patients' LDH levels. CONCLUSIONS: Our findings claim the suggestive role of HCV and occult HBV infections in NHL but not HL patients in comparison to healthy control, suggesting pre-screening of related factors including occult HBV in for potential better therapy response.

Malignant Melanoma of the Gastrointestinal Tract: Symptoms, Diagnosis, and Current Treatment Options.

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.

Survival in Good Performance Malignant Pleural Mesothelioma Patients; Prognostic Factors and Predictors of Response

Purpose: Malignant pleural mesothelioma (MPM) has a poor prognosis in general. Here we sought to evaluate prognostic factors and predictors of response to chemotherapy in good performance (PS=0-I) patients. Methods: We retrospectively reviewed our database and enrolled patients with MPM who received platinum containing chemotherapy (2012-2014). Clinico-pathological and laboratory data were retrieved and Cox and logistic regression multivariate analyses (MVA) were respectively used to identify predictors of survival and response to chemotherapy. Comparison of good vs poor performance status (PS≥II) was accomplished using the Chi (X2) test. Kaplan­Meier survival curves were also obtained and propensity-score matching was performed for survival comparison. Results: Among 114 patients listed during the study period, 82 had good PS=0-I (median age 45years, 43 men, 30 smokers, median weight=77Kg, pretreatment haemoglobin (Hb) level=12g/dL, platelet count=372,000/µL, leukocytes=9,700/µL, neutrophils=6,100/µL, lymphocytes=1,890/µL and neutrophil/lymphocyte ratio (NLR)=3.60 ). Some 65 had asbestosis, 23 had chronic disease, 55 (67.1%) were responders to platinum containing first line chemotherapy. A total of 49 (59.8%) had epithelial MPM. Median-OS and PFS in good PS cases were 17 and 9 months, respectively, as compared to 16 and 8 months for the poor PS group. After matching, better OS was observed among good PS vs poor PS patients (p=0.024) but there was no PFS difference (p=0.176). Significant decrease in PFS was observed among those with advanced nodal N disease (median PFS in N0 and N+ was 10 and 5 months, respectively), non-responders (p=0.012), NLR (p=0.026) and those with an epithelial pathology (p=0.062). MVA demonstrated that advanced (N) status (p=0.015), being a non-responder (p<0.001), NLR (p=0.015) and smoking (p=0.07) adversely affected the prognosis. The only predictor of response was absence of metastasis (M0; p=0.04). Conclusions: In addition to previously recognized factors, like nodal status, response, smoking and NLR, better median survival was evident in our patients with a good PS. Early detection before development of metastasis warrants greater focus to allow better responses to be obtained.