Response Rate Of Chemotherapy Research Articles

Effect of a multimodal intervention in breast Cancer patients undergoing neoadjuvant therapy: A study protocol of the multimodal project

Background and aimsTo determine the effect of a multimodal intervention (nutritional behavior change and physical exercise) on quality of life, chemotherapy response rate and tolerance, histopathological level of the tumor, body composition, and biochemical parameters, in patients diagnosed with breast cancer during neoadjuvant chemotherapy treatment, and to compare them with the control group. MethodsAnticipated 80 patients diagnosed with breast cancer aged 18–70 years will be recruited for this randomized, unblinded clinical trial based on a nutritional behavior change and physical exercise in patients during the approximately 6 months in which the patient receives neoadjuvant treatment. Participants will be randomly allocated (1:1) to one of two groups (intervention or control). Primary and secondary outcomes will be assessed before the beginning and after the neoadjuvant treatment (before surgery). The primary outcome is quality of life, whereas secondary outcomes include chemotherapy response rate and tolerance, histopathological level of the tumor and body composition (i.e., visceral adipose tissue activity, bone, lean and fat masses). We will analyze blood parameters (i.e., biochemical, inflammatory, and tumor markers) as exploratory outcomes. ConclusionThis study will address the influence of a practical and viable multimodal intervention (i.e., nutritional behavior change and physical exercise) on breast cancer patients undergoing neoadjuvant chemotherapy. Given the practical viability of the intervention in real-world settings, our study holds promise for significant scientific and clinical implications.

Abstract PS04-03: Survival benefit of regional nodal irradiation in clinically node-positive breast cancer following neoadjuvant chemotherapy and breast-conserving surgery

Abstract Introduction: In recent years, there has been increasing use of neoadjuvant chemotherapy (NAC) and pathologic complete response (pCR) rates for certain breast cancer phenotypes (40-70%). Although encouraging, this has resulted in uncertainties in traditional axillary management. Meanwhile, clinically node-positive (cN+) patients who have a low burden of disease downstaged to node-negative (ypN0) after NAC and get breast-conserving surgery (BCS) may avoid an axillary lymph node dissection (cALND) but still have regional nodal irradiation (RNI) recommended regardless of axillary surgery. Those who remain node-positive (ypN+) undergo cALND and RNI with an increased risk of lymphedema. In this study, we evaluated the survival benefit of RNI in cN+ patients after NAC and BCS. Methods: We reviewed (cN+) stage I-III non-inflammatory female breast cancer patients who underwent NAC followed by BCS between 2010 and 2020 in the National Cancer Database (NCDB). Patients having a history of another malignancy who received hormone therapy or radiotherapy before surgery or whose pathologic nodal status (ypN) was unknown were excluded. Overall survival (OS) from surgery was compared between those who did and did not receive RNI. Patient and tumor characteristics were compared across subgroups using chi-square and Wilcoxon rank sum tests. Weighted Kaplan-Meier curves and log-rank tests were used to assess the effect of RNI on OS. As a sensitivity analysis, analyses were stratified based on yPN status. Finally, multivariable logistic regression was used to determine predictors of receiving RNI. Results: The 8,250 cN+ patients had a mean age of 54.6±11.1 years. In total, 69.1% of patients were White, 23.9% were Black, and 10.2% were Hispanic. The mean number of removed and positive nodes were 10.0 ±7.8 and 2.3±3.8. The most common histology and phenotype were invasive ductal carcinoma (IDC) in 94.3% and hormone-positive (HR+) in 41.0%. Breast and nodal pCR rates were 25.9% and 34.7%, with nodal pCR achieved in 20.7%, 46.0%, and 44.4% of HR+, HER2+, and triple-negative tumors. RNI was performed in 52.1% of the patients (45.3% of the yPN0 and 55.9% of the yPN+). The mean number of nodes removed was 10.4±7.8 in the RNI+ and 9.6±7.7 in the RNI- groups (P < 0.01). The mean number of positive nodes was 2.6±4.0 in the RNI+ and 1.9±3.6 in the RNI- groups (P < 0.01). On multivariable analysis, the predictors of RNI administration included the number of positive nodes (p < 0.01), cN stage (p < 0.01), cT3 (p < 0.01), and tumor phenotype (p < 0.01). Grade I tumors (p=0.04) and Medicare beneficiaries (p=0.01) were less likely to get RNI. The survival rates were 79.9% and 81.9% in the RNI+ and RNI– groups, with a median follow-up of 62.1±31.4 and 62.8±32.2 in the RNI+ and RNI- groups. In the entire cohort, ypN0 patients had improved OS when compared with ypN+ patients (p < 0.001), but in adjusted analyses, there was no difference in OS between those who did and did not receive RNI (p=0.6). There was also no difference in OS comparing those who did and did not receive RNI in the ypN0 (p=0.96) or ypN+ (p=0.76) groups. Conclusion: For breast cancer patients having a modest nodal burden of disease and BCS after NAC, traditional prognostic factors such as stage and nodal status, as well as phenotype, grade, and the presence or absence of pCR, impact overall survival. Although some such factors appear to bias practitioners into giving RNI for patients undergoing NAC and BCS, RNI after NAC and BCS does not improve OS, regardless of pCR status, even at a mean follow-up time of 5.5 years. Further studies evaluating the impact on local control and longer-term outcomes should be pursued to enable the creation of specific guidelines surrounding indications for RNI based on the initial burden of disease and the final response from NAC administration. Citation Format: Mahtab Vasigh, Richard Bleicher, Austin Williams, Allison Aggon, Mary Pronovost, Andrea Porpiglia, Matthew Pierotti, Christian Cruz Pico. Survival benefit of regional nodal irradiation in clinically node-positive breast cancer following neoadjuvant chemotherapy and breast-conserving surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS04-03.

Myelodysplasia-related gene mutations are associated with favorable prognosis in patients with TP53-mutant acute myeloid leukemia.

This study aimed to examine the characteristics and treatment outcomes of patients with TP53-mutant acute myeloid leukaemia (AML) and to explore potential prognostic factors. This retrospective analysis included 130 patients diagnosed with TP53-mutant AML at the Fujian Medical University Union Hospital between January 2016 and June 2023. Patients' ages ranged from 17 to 80 years, with a median age of 59 years. The proportions of de novo, therapy-related, and secondary AML cases were 71.5%, 7.7%, and 20.8%, respectively. Complex karyotypes were observed in 60.6% of patients, and the proportions of -5 or del(5q), -7 or del(7q), and - 17 or del(17p) were 41.7%, 27.9% and 14.4%, respectively. DNA methylation- and myelodysplasia-related (MR) gene mutations were observed in 36.9% and 25.4% of patients, respectively. These patients showed poor survival, with a median overall survival (OS) of 4.5 months, a 1-year OS rate of 32.5%, a 3-year OS rate of 18.8%, and a 5-year OS rate of 11.3%. The complete response rates for intensive chemotherapy (IC), hypomethylating agent (HMAs)-based therapies, and azacitidine plus venetoclax were 35.7%, 22.2%, and 37.5%, respectively. Patients who did or did not receive allogeneic haematopoietic stem cell transplantation (allo-HSCT) had similar prognoses (median OS: 6.0 vs. 3.9 months; P = 0.6415). Multivariate analysis indicated that MR gene mutations is an independent favorable prognostic factor of OS (HR = 0.366, 95% CI: 0.181-0.738, P = 0.005). In conclusion, patients with TP53-mutant AML have poor prognoses under current treatment strategies and MR gene mutations are associated with a more favorable survival. Therefore, further studies are needed to improve the survival rates in this population.

Abstract B059: A novel pancreatic cancer mouse model with human immunity

Abstract The iRGD tumor-penetrating peptide delivers chemically linked drugs and even co-injected free drugs selectively to extravascular tumor tissue by targeting the αvβ5 integrin and neuropilin-1 (NRP1). A phase 1b clinical trial showed that iRGD appears to safely double the response rate of standard chemotherapy in patients with stage 4 pancreatic ductal adenocarcinoma (PDAC). We recently found that long-term iRGD treatment, even as a monotherapy, reduced regulatory T cells (Tregs) selectively in the PDAC tissue, which led to the expansion of CD8+ T cells and improved efficacy of immunotherapy in syngeneic PDAC mice. This finding led to the discovery of αvβ5 integrin being a novel targetable marker for tumor-resident Tregs in PDAC mice. Our recent data show that αvβ5 integrin+ Tregs are also present in human PDAC tissue. To study the significance of αvβ5 integrin+ human Tregs as a therapeutic target for iRGD, we developed a humanized PDAC (huPDAC) mouse model by transplanting human PDAC cells into human immune system (HIS) mice, which harbor fully matured human CD8+ and CD4+ T cells, natural killer T cells, B cells, and dendritic cells. The CD8+ T cells are human leukocyte antigen (HLA)-restricted and show a tumor antigen-specific response. We orthotopically implanted HLA-matched human PDAC cells into HLA-A2-positive HIS mice. Both an established human PDAC cell line (PANC-1) and patient-derived PDAC cells (0779E) successfully formed orthotopic tumors and liver metastases. The tumors were infiltrated by various human immune cells at a ratio similar to that found in patient-derived PDAC tissues. Of note, αvβ5 integrin+ human Tregs were also noted in the tumors but not in the spleen. iRGD monotherapy increased the ratio of CD8+ T cells per Tregs in the tumors, suggesting that iRGD will likely function as an immunomodulator in humans. The first patient was recently dosed in a new phase 1b/2a clinical trial (iLSTA Trial: ACTRN12623000223639), which assesses the safety and preliminary efficacy of iRGD in combination with standard-of-care chemotherapy and immunotherapy in locally advanced PDAC patients. Citation Format: Norio Miyamura, Kodai Suzuki, Richard A. Friedman, Aristidis Floratos, Yuki Kunisada, Kazuya Masuda, Andrew M. Lowy, Moriya Tsuji, Kazuki N. Sugahara. A novel pancreatic cancer mouse model with human immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B059.

Clinical Observation of Camrelizumab (CAM) Combined with Bendamustine and Gemcitabine (BeGe) in Relapsed/Refractory Classical Hodgkin Lymphoma (cHL): A Phase II Trial

Background The cure rate of classical Hodgkin's lymphoma (cHL) is more than 80%. However, 20% or so of cHL patients have refractory or recurring disease, making clinical treatment complex and challenging. Currently, the standard treatment for patients with r/r-cHL is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDCT/ASCT). However, the complete response rate of traditional salvage chemotherapy is not ideal, which prevents some patients from receiving stem cell transplantation. In recent years, with the application of new drugs such as PD1 inhibitors, the efficacy of R/R cHL has been further improved. we designed a prospective, single-arm, multi-center trial to evaluate the efficacy and safety of PD-1 antibody camrelizumab combined with bendamustine and gemcitabine（BeGe）in patients with relapsed or refractory (r/r) classical Hodgkin Lymphoma (cHL). Methods This research is a phase 2 exploratory, open-label, multi-center study. Key inclusion criteria include age≥18 and ≤75, ECOG<2, R/R cHL who had received at least first-line chemotherapy, at least one measurable lesion per Lugano criteria 2014, and preparing to receive autologous stem cell transplantation (ASCT). Patients were treated with camrelizumab (CAM, 200 mg IV, day 1 q3w) combined with bendamustine （90mg/m 2, IV, day 2 and Day3) and gemcitabine (1000 mg/m 2 day 1 and day4) for 2 cycles. Patients with complete response (CR) underwent autologous hematopoietic stem cell transplantation after high-dose chemotherapy (HDT/ASCT). Patients who did not achieve CR underwent HDT/ASCT if CR was attained after two additional cycles of CAM plus BeGe. 1-2 cycles of CAM monotherapy were permitted for individuals who were waiting more than 4 weeks for ASCT. The primary endpoint was the proport ion of patients who achieved PET-CT-confirmed complete response (CR) according to Lugano 2014 criteria. Results 17 individuals were enrolled between February 2022 and May 2023, including 5 relapsed and 12 refractory patients. 14 (82.4%) of the enrolled patients were younger than 60 years old, with a median age of 37 years (range: 20-62) and 76.5% male. 12 patients had received first-line prior therapy, and 5 patients had received second-line therapy or more. After 2 cycles CAM plus BeGe, Overall response rate (ORR) was 94.0% (16/17) with CR rate of 64.7% (11/17) and PR rate of 29.4% (5/17). Only one patient withdrew from the study because to progressive disease (PD). 4 patients who achieved PR received 2 additional cycles of CAM plus BeGe, and 2 patients achieved CR. Up to now, autologous hematopoietic stem cell transplantation has been carried out in 7 patients, with stem cell being collected from 5 patients after 2 cycles and 2 patients after 4 cycles. With a cutoff date of June 10, 2023, the 1-year (progression-free survival) PFS rate was 86.3% and the 1-year (overall survival) OS rate was 94.1%. One patient experienced grade 3 pancreatitis. Grade 1-2 AE occurred in 9 patients, and common AEs included pruritus(4/17), pyrexia(4/17), bone marrow suppression(2/17), nausea(1/17), diarrhea(1/17), mild reactive cutaneous capillary endothelial proliferation(RCCEP, 1/17). No grade 4 or above AEs occurred. Conclusion It is well known that refractory cases are more difficult to treat and have a worse prognosis than relapsed cases. Despite the preponderance of refractory cases in this study, the response was excellent. Therefore, Camrelizumab combined with BeGe chemotherapy patients shows encouraging clinical efficacy and safety in R/R HL, and has no significant effect on stem cell collection, which is worthy of further study.

The Efficacy and Prognosis of Advanced Myelodysplastic Syndrome in Children

Pediatric myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell neoplasm with an annual incidence of 1-4 cases/million. The low incidence of advanced MDS in children and poor prognosis attract our attention. However, there are limited reports on the scheme and efficacy of pediatric advanced MDS. In this study, we retrospectively analyzed the efficacy of chemotherapy in pediatric advanced MDS and assessed the prognosis of patients. According to 2016 World Health Organization (WHO) classification of haematolymphoid tumours, 30 newly diagnosed pediatric advanced MDS patients during Dec 2007 to Apr 2022 from our single center were selected as the research object. The clinical data and prognosis were analyzed. The median age of patients is 8 years (range: 1-15years). The median bone marrow blast is 15.75% (range: 5-29.5%), while the median peripheral blood blast is 4% (range: 0-29%). Cytogenetic analysis was available for 29 patients, 69% (20/29) cases had abnormal karyotype. Monosomy 7 (37.9%) was the most common cytogenetic abnormality. Out of the total, 7 patients were treated with CAG/HAG regimen (C: aclarubicin 6mg d1-14, H: homoharringtonine 1mg/m 2d1-14, A: cytarabine 10mg/m 2 q12h d1-14, and G: Granulocyte Colony-stimulating Factor 200mg/m 2 d1-14 ), 8 patients with decitabine (20mg/m 2 d1-5), 11 patients with decitabine and CAG/HAG, 4 patients with AML-like chemotherapy (Daunorubicin+cytarabine+etoposide ) or other. The evaluation of response of therapy was available in 25 patients, 5 cases (20%) in partial remission (PR), 11 cases (44%) in complete remission (CR), 9 cases in(36%)non-remission (NR). The total response rate of chemotherapy is 60%, with CAG/HAG therapy 33%, decitabine therapy 43%, combined CAG/HAG and decitabine therapy 78%, AML-like chemotherapy 100%. The total complete remission rate of chemotherapy is 44%, with CAG/HAG therapy 17%, decitabine therapy 43%, combined CAG/HAG and decitabine therapy 56%, AML-like chemotherapy 67%. Patients receiving CAG/HAG in combination with decitabine had higher response rates compared to CAG/HAG or decitabine alone (OR=17.5, 95% CI 1.2-250.3, P=0.035). With a median follow-up of 20 months (range: 1-158months), 23 patients received HSCT after chemotherapy, and they had a higher 2-year overall survival rate compared to those who did not undergo transplantation (86% vs 0%, p<0.001). Decitabine combined with CAG/HAG improve the response rate of advanced pediatric MDS. Chemotherapy bridged hematopoietic stem cell transplantation significantly improves the prognosis of advanced pediatric MDS.

OGC P37 Long term follow-up of patients undergoing prehabilitation prior to oesophagectomy: What happens to patients declining or withdrawing from prehabilitation exercise programmes?

Abstract Background Prehabilitative exercise prior to cancer surgery can improve survival, health-related quality of life and chemotherapy completion and response rates. Little is known about patients who either drop-out or decline to participate in exercise programmes in oesophageal cancer. This study reports the outcomes of patients who declined or dropped out of the Pre-EMPT trial prior to neo-adjuvant chemotherapy (NAC) and oesophago-gastrectomy. Methods A prospective non-randomised, cohort-controlled trial compared a standard care pathway (control) to a structured prehabilitation exercise programme (intervention) commenced before NAC and surgery for oesophageal cancer. Kaplan-Meier and multivariable Cox regression analyses were used to compare overall and disease-free survival between the trial patients (intervention and control) with patients who declined participation or dropped out of the study (non-participants). Results 21 patients completed the exercise intervention, 20 patients were enrolled in the control group, and 24 patients either dropped out (9) or declined to participate (15). All underwent NAC and oesophago-gastrectomy. Baseline comorbidity, post-operative complication rates and length of stay were similar between all groups. Kaplan Meier survival analysis showed no difference between the intervention and control groups but a significant survival disadvantage in the non-participants (p=0.03). On multivariable analysis mortality hazard ratio was significantly higher in the non-participant group (HR 95%CI3.44; 1.05-11.28). Conclusions Patients who dropped out or declined to participate in the PRE-EMPT study experienced poorer survival compared to both the intervention and control groups. This survival disadvantage is likely to be multifactorial. However, these patients represent an important group, currently inaccessible to prehabilitative programmes, who may have the most to gain from such an intervention.

Clinical Characteristics, Response to Platinum-Based Chemotherapy and Poly (Adenosine Phosphate-Ribose) Polymerase Inhibitors in Advanced Lung Cancer Patients Harboring BRCA Mutations.

The oncogenic role and clinical relevance of BRCA mutations in NSCLC remain unclear. We aim to evaluate the characteristics and clinical outcomes of patients with NSCLC harboring BRCA mutations treated at Hadassah Medical Center (HMC). We retrospectively assessed all patients with advanced NSCLC who underwent next-generation sequencing (NGS) and were found to have pathogenic somatic BRCA mutations (p-BRCA). We compared clinical outcomes in NSCLC patients with wild-type BRCA (wt-BRCA) matched by age, stage, gender, smoking, PDL-1 and driver mutations. Between 2015 and 2022, we evaluated 598 patients with advanced NSCLC using NGS and found 26 patients with p-BRCA, of whom 17 (65.4%) were carriers of germline BRCA variants and represented 1% of all BRCA carriers HMC. The median age of diagnosis was 67 years old (40-78), 13 patients (50%) had a history of smoking and 9 patients (34.6%) had additional driver mutations (EGFR, ALK, BRAF, MET or ERBB2). Objective response rate and median progression-free survival (PFS) for first-line platinum-based chemotherapy in the p-BRCA group compared to wt-BRCA controls were 72.2% and 16 months (CI 95%, 5-22), compared to 47.4% and 7 months (CI 95%, 5-9), respectively, and HR for PFS was 0.41 (CI 95%, 0.17-0.97). Six patients in the p-BRCA group were treated with advanced-line poly (adenosine-phosphate-ribose) polymerase inhibitors (PARPi), with a durable response observed in four patients (66%). In this cohort, patients with NSCLC harboring p-BRCA exhibit high-sensitivity PARPi and a prolonged response to platinum, suggesting some oncogenic role for BRCA mutations in NSCLC. The results support further prospective trials of the treatment of NSCLC harboring p-BRCA with PARPi.

Prognostic Factors of Chemotherapy Response and Survival in Non-Small Cell Lung Cancer: Data from Real-World Practice with Limited Access to Novel Therapy

Background: Chemotherapy is a backbone treatment in advanced-stage non-small cell lung cancer (NSCLC) for non-targetable mutations and inaccessible to novel therapies. However, the data on the response rate, factors of chemotherapy response, and survival in Thailand are limited. Objective: To find the chemotherapy response rate, factors that predict chemotherapy response and survival in advanced-stage NSCLC. Materials and Methods: A retrospective cohort study was performed by including advanced-stage NSCLC patients older than 18 years old who received chemotherapy at the medical oncology unit, Sawanpracharak Hospital between July 2014 and January 2020. Demographic data, laboratory data, details of treatment, computed tomography (CT) of chest, and survival time were collected. Descriptive statistical analyses followed by univariable and multivariable were performed to determine factors associated with chemotherapy response. Kaplan-Meier survival curve was used to estimate overall survival (OS), and the log-rank test was performed to compare survival differences in each group. The univariable and multivariable Cox regression method was adopted for OS. Results: Tree hundred four chemotherapy-treated advanced-stage NSCLC were included. The chemotherapy response rate was 45.5%, and ECOG 0-1 was a favorable prognosis for chemotherapy response (OR 3.03, 95% CI 1.480 to 7.370, p=0.004). Pericardial metastasis (HR 1.833, 95% CI 1.102 to 3.215, p=0.021), liver metastasis (HR 2.05, 95% CI 1.131 to 3.201, p=0.002), non-objective response rate (ORR) for chemotherapy (HR 1.429, 95% CI 1.099 to 1.859, p=0.008) were worse prognosis factors. Obtaining second-line and third-line systemic treatment were favorable prognoses of survival in advanced-stage NSCLC (HR 0.476, 95% CI 0.348 to 0.651, p<0.001 and HR 0.247, 95% CI 0.123 to 0.494, p<0.001, respectively). Conclusion: The response rate in chemotherapy-treated advanced-stage NSCLC was 45.5%. ECOG 0-1 was an independent factor in chemotherapy response. Liver metastasis, pericardial metastasis, no subsequent treatment, and poor response to chemotherapy were worse prognosis outcomes in advanced-stage NSCLC. Keywords: NSCLC; Advanced-stage; Factor of chemotherapy response; Factor of survival

Expert Recommendations for the Diagnosis, Treatment, and Management of Adult B-Cell Acute Lymphoblastic Leukemia in Latin America.

Despite strong induction chemotherapy response rates, only 30%-40% of patients with adult B-cell acute lymphoblastic leukemia (ALL) attain long-term remission. This study analyzes ALL in Latin America (LA) and recommends diagnosis, treatment, and management protocols. The Americas Health Foundation organized a panel of hematologists from Argentina, Brazil, Chile, Colombia, and Mexico to examine ALL diagnosis and therapy and produce recommendations. Lack of regional data, unequal access to diagnosis and therapy, inadequate treatment response, and uneven health care distribution complicate adult ALL management. The panel recommended diagnosis, first-line and refractory treatment, and post-transplantation maintenance. Targeted treatments, including rituximab, blinatumomab, and inotuzumab ozogamicin, are becoming available in LA and must be equitably accessed. This review adapts global information on treating ALL to LA. Governments, the medical community, society, academia, industry, and patient advocates must work together to improve policies.

Effect of neoadjuvant chemotherapy combined with arterial chemoembolization on short-term clinical outcome of locally advanced gastric cancer

BackgroundThe purpose of this study was to explore the short-term efficacy and safety of neoadjuvant chemotherapy combined with arterial chemoembolization for locally advanced gastric cancer (LAGC).MethodsWe retrospectively analyzed the clinical data of 203 patients with LAGC who received neoadjuvant therapy from June 2019 to December 2021. The patients were divided into a neoadjuvant chemotherapy combined with arterial chemoembolization group (combined group, n = 102) and a neoadjuvant chemotherapy group (conventional group, n = 101). The adverse events of chemotherapy, postoperative complications and pathological complete response (pCR) rate were compared between the two groups. Univariate and multivariate analyses were performed to evaluate the potential factors affecting pCR.ResultsA total of 78.8% of the patients were in clinical stage III before neoadjuvant therapy. A total of 52.2% of the patients underwent surgery after receiving two cycles of neoadjuvant therapy. There were 21.2% patients with ≥ grade 3 (CTCAE 4.0) adverse events of chemotherapy and 11.3% patients with Clavien-Dindo classification ≥ grade 3 postoperative complications. Compared with the conventional group, the combination group did not experience an increase in the adverse events of chemotherapy or postoperative complications. The pCR rate in the combined group was significantly higher than that in the conventional group (16.7% vs. 4.95%, P = 0.012). The multivariate analysis showed that arterial chemoembolization, pre-treatment neutrophil-to-lymphocyte ratio (NLR) and pre-treatment platelet-to-lymphocyte ratio (PLR) were independent factors affecting pCR.ConclusionNeoadjuvant chemotherapy combined with arterial chemoembolization contributed to improving the pCR rate of LAGC patients. Arterial chemoembolization, pre-treatment NLR and pre-treatment PLR were also predictors of pCR.

Epidemiology, risk factors and impact of cachexia on patient outcome: Results from the Japanese Lung Cancer Registry Study.

Cancer cachexia is a syndrome that does not fully recover with nutritional support and causes appetite loss and body weight loss. It worsens a patient's quality of life and prognosis. In this study, the epidemiology of cachexia in lung cancer, its risk factors and its impact on chemotherapy response rate and prognosis were examined using the national database of the Japan Lung Cancer Society. Understanding these things related to cancer cachexia is important as a starting point in overcoming cancer cachexia in patients with lung cancer. In 2012, 12320 patients from 314 institutions in Japan were registered in a nationwide registry database (Japanese Lung Cancer Registry Study). Of these, data on body weight loss within 6months were available for 8489 patients. We defined the patients with body weight loss≥5% within 6months, which is one of the three criteria listed in the 2011 international consensus definition of cancer cachexia, as cachectic in this study. Approximately 20.4% of the 8489 patients had cancer cachexia. Sex, age, smoking history, emphysema, performance status, superior vena cava syndrome, clinical stage, site of metastasis, histology, epidermal growth factor receptor (EGFR) mutation status, primary treatment method and serum albumin levels were significantly different between patients with and without cachexia. Logistic analyses showed that smoking history, emphysema, clinical stage, site of metastasis, histology, EGFR mutation, serum calcium and albumin levels were significantly associated with cancer cachexia. The response to initial therapy, including chemotherapy, chemoradiotherapy or radiotherapy, was significantly poorer in the patients with cachexia than in those without cachexia (response rate: 49.7% vs. 41.5%, P<0.001). Overall survival was significantly shorter in the patients with cachexia than in those without cachexia in both univariate and multivariable analyses (1-year survival rate: 60.7% vs. 37.6%, Cox proportional hazards model, hazard ratio: 1.369, 95% confidence interval: 1.274-1.470, P<0.001). Cancer cachexia was seen in approximately one fifth of the lung cancer patients and was related to some baseline patient characteristics. It was also associated with a poor response to initial treatment, resulting in poor prognosis. The results of our study may be useful for early identification and intervention in patients with cachexia, which may improve their response to treatment and their prognosis.

Role of KI67 in response rate of neoadjuvant chemotherapy in hormonal positive breast cancer

Introduction: A pathological complete response (pCR) after neo-adjuvant chemotherapy indicates that the outlook for individuals with breast cancer is encouraging. identifying factors, for instance the growth biomarker Ki67, that could forecast pCR, can be useful for improving understanding how drug reaction affects outcome. This research aims to evaluate Ki67's prognostic as well as prediction utility in infiltrating breast cancer patients receiving neoadjuvant treatment. Methods: After fixation and embedding, the researchers performed Ki67 staining on core biopsies taken from 552 patients. They also evaluated HER2/neu, oestrogen, progesterone receptors, and graded the samples prior to therapy. They created both univariate and multivariate models to forecast pCR and prognosis using this data. They also divided the tumors into various molecular phenotypes in order to find possible subgroups in which Ki67 could be used to forecast pCR and prognosis. Results: The researchers discovered that Ki67 was a significant autonomous pCR predictor (OR 4; 94.7% CI, 1.3 , 9), overall survival (HR 9; 96% CI, 4 to 21), and survival without illness (HR 3; 96% CI, 2 to 6) utilizing a cut-off value of &gt; 14% positive neoplasic cell staining.

Hemoglobin and Neutrophil Count as Prognostic Factors in Cholangiocarcinoma Patients in 2nd Line Treatment Setting: Results from a Small Monocentric Retrospective Study.

Unresectable cholangiocarcinoma prognosis can be extremely variable due to different symptoms and sites of disease involvement at diagnosis and unpredictable chemotherapy response rates. Most patients will usually receive 1st line palliative chemotherapy with platinum compounds and Gemcitabine or Gemcitabine alone. Only a few patients maintain adequate performance status after first-line treatment failure: second-line treatment with FOLFOX or FOLFIRI chemotherapy has been used in this setting with modest overall survival improvement. There is a lack of data concerning whether laboratory findings might help clinicians in identifying those patients with the highest likelihood of benefiting from 2nd line treatment. The aim of this analysis is to assess the prognostic role of a series of easily available laboratory tests in patients with bile duct cancer who received 2nd line chemotherapy. Patients with unresectable bile duct cancer treated in 2nd-line setting with platinum-based chemotherapy doublet or FOLFIRI were enrolled. The primary objective of the analysis was to assess overall survival (OS) differences among patients based on the results of lab tests. Serum hemoglobin, neutrophil, lymphocyte, monocyte, platelet absolute count, creatinine, total bilirubin, albumin, LDH, circulating CEA and CA19.9 values were collected at the start of 2nd line treatment. Cut-off values for all lab tests were set by ROC curve analysis. Survival was calculated by the Kaplan-Meier method and differences in survival among stratification factors were assessed by Log-rank test. Cox-proportional-hazard regression was used for multivariate analysis. Level of statistical significance p was set at 0.05 for all tests. Correction for false discovery error rate was performed by Holm's stepdown procedure. A total of 46 patients were eligible. Median overall survival of the entire cohort was 8.98 months (95%CI: 6.68-13.93) while mean OS was 17.10 months (standard error: 3.16). Using 6.2 months OS landmark as classification variable for ROC curve analysis, only serum hemoglobin (cut-off: &gt;10 g/dL), albumin (cut-off: &gt;3.5 mg/dL), CA19.9 (cut-off: ≤668 UI/mL), monocyte (cut-off: ≤510/mmc) and neutrophil count (cut-off: ≤5140/mmc) were significantly associated with the chosen end-point. Multivariate analysis confirmed an independent statistically significant impact on overall survival only for hemoglobin (Exp(b): 0.12, p = 0.0023) and neutrophil count (Exp(b): 0.30, p = 0.0039). Based on these results, using both hemoglobin and neutrophil count, three prognostic groups were defined: patients with both favorable factors had 12.63 months median OS vs. 6.75 months of patients with only one favorable factor vs. 1.31 months of those with neither. The difference between these three groups of patients was statistically significant (p &lt; 0.0001). Second-line palliative chemotherapy can be a potentially useful option for a few patients with unresectable/metastatic bile duct cancer. Even though assessment of patients' prognosis might be difficult due to the complex behavior of this disease, a series of easily available laboratory tests might be used for these means: serum hemoglobin and neutrophil count we0re able to define subsets of patients with entirely different prognoses. It is hoped that this score will be prospectively validated in a larger group of patients in order to improve treatment decisions in patients with unresectable bile duct cancer candidate to receive palliative 2nd line chemotherapy.

The comparative study for survival outcome of locally advanced cervical cancer treated by neoadjuvant arterial interventional chemotherapy or intravenous chemotherapy followed by surgery or concurrent chemoradiation

ObjectiveThis study aimed to compare the survival outcome of 3 different treatment groups (arterial interventional chemotherapy or intravenous chemotherapy or concurrent chemoradiotherapy) for locally advanced cervical cancer.MethodsA total of 187 patients with pathological stage IB3–IIB cervical cancer (cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma) hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2013 to May 2019 were included. Therefore, this article is a retrospective study. We collected data from all eligible patients. And all according to the treatment methods at that time, they were divided into three subgroups: (1) 40 patients who received neoadjuvant arterial interventional chemotherapy + surgery + postoperative chemotherapy (IA-NAC + RS), (2) 63 patients who received neoadjuvant intravenous chemotherapy + surgery + postoperative chemotherapy (IV-NAC + RS), (3) 84 patients who only received concurrent chemoradiotherapy (CCRT). Notably, 108 of these patients met the 5-year follow-up period, and 187 patients met the 3-year follow-up period only. Consequently, we compared 5-year survival and 3-year survival separately. The prognosis (5-year survival and 3-year survival) of the three groups and the chemotherapy efficacy, intraoperative blood loss, operation time, and postoperative pathological risk factors of different subgroups were compared.Results(1) There were no significant differences in the 3-year overall survival (OS) rate, 3-year progression-free survival (PFS) rate, 5-year OS rate, and 5-year PFS rate among the three subgroups (p > 0.05). (2) The chemotherapy response rates of IA-NAC+RS group (37.5%) and IV-NAC+RS group (25.4%) were comparable (p > 0.05). (3) The intraoperative blood loss in the IA-NAC+RS group (average 92.13±84.09 mL) was significantly lower than that in the IV-NAC+RS group (average 127.2±82.36 mL) (p < 0.05). (4) The operation time of the IA-NAC+RS group (average 231.43±63.10 min) and the IV-NAC+RS group (average 219.82±49.11 min) were comparable (p > 0.05). (5) There were no significant differences between the IA-NAC+RS group and IV-NAC+RS group in pathological lymph node metastasis, parametrial invasion, and involvement of lymphovascular space (p > 0.05).ConclusionsNeoadjuvant chemotherapy combined with surgery had the same long-term survival benefit as concurrent chemoradiotherapy.

Efficacy and Safety of Immune Checkpoint Inhibitors in Triple-negative Breast Cancer: A Study Based on 41 Cohorts Incorporating 6558 Participants.

The project was designed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC). Electronic databases were screened to identify relevant trials. The primary endpoints were prognostic parameters and adverse events (AEs) through pooled rate, odds ratio, and hazard ratio (HR) with 95% CI. Totally, 6558 TNBC patients from 41 cohorts were included. The pooled pathologic complete response rate (odds ratio=2.03, 95% CI: 1.35-3.06, P =0.0007) and event-free survival (HR=0.84, 95% CI: 0.73-0.96, P =0.0100) of ICIs plus chemotherapy was higher than that of chemotherapy-alone in early-stage TNBC. For metastatic TNBC, compared with chemotherapy-alone, the addition of ICIs prolonged the progression-free survival (PFS) (HR=0.92, 95% CI: 0.88-0.96, P <0.0001); the improvement also existed in the following 3 subgroups: programmed cell death-ligand 1 positive, race of White and Asian, and patients without previous neoadjuvant or adjuvant chemotherapy; however, the benefit of the combined regimen was not observed in overall survival (OS) (HR=0.95; 95% CI: 0.89-1.03, P =0.2127). In addition, the pooled rates of OS, PFS, and objective response rate of ICIs plus chemotherapy were better than those of ICIs plus targeted therapy or ICIs-alone. In the safety analysis, compared with chemotherapy-alone, ICIs plus chemotherapy increased immune-related AEs and several serious AE. The regimen of ICIs plus chemotherapy is promising in both early-stage and metastatic TNBC, while the increased serious AE should not be neglected. Furthermore, the pooled rates of OS, PFS, and objective response rate of ICIs plus chemotherapy were better than those of ICIs plus targeted therapy or ICIs-alone.

Re-challenging chemotherapy after pembrolizumab in platinum-refractory urothelial carcinoma.

To assess the real-world clinical benefit of re-challenging chemotherapy after pembrolizumab in patients with metastatic urothelial carcinoma (mUC), as there have been several reports suggesting that programmed cell death protein-1/programmed death-ligand 1inhibitors can restore platinum sensitivity. Of 236 patients treated with pembrolizumab, we excluded 45 patients who did not experience progressive disease (PD) for pembrolizumab during the follow-up and 86 patients who discontinued pembrolizumab by the diagnosis of PD followed by the best supportive care. A total of 105 patients were identified for a logistic regression propensity score model to compare the survival outcomes between patients treated with continuing pembrolizumab (80) and re-challenging chemotherapy (25) after the diagnosis of PD for pembrolizumab. A median overall survival (OS) from PD for pembrolizumab was 11 months in 105 patients. Of 25 patients treated with re-challenging chemotherapy, platinum-including chemotherapy (gemcitabine and cisplatin; gemcitabine/cisplatin/paclitaxel [GCP]; methotrexate and vinblastine and adriamycin and cisplatin; and methotrexate and carboplatin and vinblastine MCAVI) was offered in 20 patients (80%). The objective response rate (ORR) for the first-line chemotherapy in the 105 patients was 30%, with a comparable ORR in 25 patients treated with re-challenging chemotherapy of 28%. GCP as a re-challenging regimen was offered in 12 of 25 (48%) patients. The ORR for the GCP regimen was 50%. Propensity score matching was performed using putative clinical factors, from which 34 patients were identified as pair-matched groups. The OS for patients treated with re-challenging chemotherapy was significantly longer than continuing pembrolizumab (a median of 13.9 and 5.8 months, respectively: P = 0.048). Re-challenging chemotherapy including platinum agents after PD with pembrolizumab offers clinical benefits in patients with mUC.

Efficacy and safety of neoadjuvant Folfirinox and Gemcitabine plus Nab-Paclitaxel for borderline resectable and locally advanced pancreatic cancer: a systematic review and meta-analysis.

Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic cancer. However, the efficacy and safety of Folfirinox and GNP as NAC for BRPC and LAPC is still controversial. The eligible studies including prospective, retrospective, and randomized controlled trial related to Folfirinox and GNP as NAC for patients with BRPC or LAPC up to March 2022 were searched and assessed. Pooled analysis for chemotherapy response rate, resection rate, R0 resection rate, progress free survival, overall survival, and grade 3/4 events of toxicity were performed in the study. Eight studies were included in this meta-analysis. Compared with GNP, Folfirinox had higher resection rate (HR=0.82; 95% CI 0.59-1.14) and R0 resection rate (HR=0.77; 95% CI 0.60-0.97), better PFS (HR=0.78; 95% CI 0.55-1.12) and OS (HR=0.68; 95% CI 0.46-0.99), and without increasing severe toxicity rate (HR=0.95; 95% CI 0.71-1.28). There are no differences in rate of stable disease (HR=1.06; 95% CI 0.92-1.22) and partial/complete regression (HR=0.85; 95% CI 0.59-1.23) between two groups. Higher resection and R0 resection rate and better PFS and OS results were obtained in Folfirinox group compared with GNP group for patients with BRPC and LAPC. There was no increased severe toxicity rate for Folfirinox compared with GNP.

Tumor-infiltrating immune cells based TMEscore and related gene signature is associated with the survival of CRC patients and response to fluoropyrimidine-based chemotherapy.

BackgroundTumor-infiltrating immune cells (TIICs) are associated with chemotherapy response. This study aimed to explore the prognostic value of a TIIC-related tumor microenvironment score (TMEscore) in patients with colorectal cancer (CRC) who underwent chemotherapy and construct a TMEscore-related gene signature to determine its predictive value.MethodsGene profiles of patients who underwent fluoropyrimidine-based chemotherapy were collected, and their TIIC fractions were calculated and clustered. Differentially expressed genes (DEGs) between clusters were used to calculate the TMEscore. The association between the TMEscore, chemotherapy response, and survival rate was analyzed. Machine learning methods were used to identify key TMEscore-related genes, and a gene signature was constructed to verify the predictive value.ResultsTwo clusters based on the TIIC fraction were identified, and the TMEscore was calculated based on the DEGs of the two clusters. The TMEscore was higher in patients who responded to chemotherapy than in those who did not, and was associated with the survival rate of patients who underwent chemotherapy. Three machine learning methods, support vector machine (SVM), decision tree (DT), and Extreme Gradient Boosting (XGBoost), identified three TMEscore-related genes (ADH1C, SLC26A2, and NANS) associated with the response to chemotherapy. A TMEscore-related gene signature was constructed, and three external cohorts validated that the gene signature could predict the response to chemotherapy. Five datasets and clinical samples showed that the expression of the three TMEscore-related genes was increased in tumor tissues compared to those in control tissues.ConclusionsThe TIIC-based TMEscore was associated with the survival of CRC patients who underwent fluoropyrimidine-based chemotherapy, and predicted the response to chemotherapy. The TMEscore-related gene signature had a better predictive value for response to chemotherapy than for survival.

Assessment of Response Rate and Toxicity in Locally Advanced Squamous Cell Carcinoma Cervix with Induction Chemotherapy Followed by Radiotherapy in Comparison with Concurrent Chemoradiation

Objective: To compare the toxicity, response rate, and survival of concurrent chemo radiotherapy and induction chemotherapy followed by radiotherapy alone in squamous cell cervical cancer patients. Place and duration of study: Radiation Oncology Department of Nishtar Hospital for 1 year Study design: A comparative retrospective study Methodology: A total of 60 women were included in the study who have been diagnosed with stage IB2 to stage IIIB squamous cell cervical carcinoma. After passing the inclusion and exclusion criteria, patients were divided into two groups, a concurrent chemo radiotherapy group (30 patients) and a radiotherapy group (30 patients) by consecutive data sampling. All the patients were subject to external beam radiotherapy to the 45 Gy to whole pelvis with 15 MV X-rays 5 days/week by using the four-field technique. The patients in the radiotherapy group were given induction chemotherapy with cisplatin 50 mg/m2 every 21 days with paclitexal 175mg/m2 (2 cycles) followed by radiotherapy alone. For the patients of concurrent chemo radiotherapy, patients were administered 40 mg/m2 cisplatin weekly with radiations for 5 cycles. Results: The overall response rate for CCRT group and RT group was 65% (n=30) and 50% (n=30) respectively. The overall survival rate was 12 months and 8 months for the CCRT group and RT group respectively. Similarly, relapse-free survival was 10 months in CCRT patients and 6 months in RT patients. The rate of hematological toxicities was more in CCRT patients. The most common adverse effect was diarrhea with 3 (10%) patients in the CCRT and 2 (6.6%) patients in the RT group. No deaths occurred due to treatment. Conclusion: The efficacy and toxicity of CCRT show promising results in squamous cell cervical carcinoma patients as compared to induction chemotherapy followed by radiotherapy treatment alone. Keywords: Concurrent chemoradiotherapy. Radiotherapy, squamous cell cervical carcinoma, toxicity