Preoperative Chemotherapy In Patients Research Articles

MBCL-02. ROLE OF PREOPERATIVE CHEMOTHERAPY IN METASTATIC MEDULLOBLASTOMA: A COMPARATIVE STUDY IN 92 CHILDREN

BACKGROUNDPrevious pilot studies have shown the feasibility of preoperative chemotherapy in patients with medulloblastoma, but benefits and risks compared with initial surgery have not been assessed.METHODSTwo therapeutic strategies were retrospectively compared in 92 patients with metastatic medulloblastoma treated at Gustave Roussy, France, between 2002 and 2015: surgery at diagnosis (n=54; group A) and surgery delayed after carboplatin and etoposide-based preoperative therapy (n=38; group B). Treatment strategies were similar in both groups.RESULTSThe rate of complete tumor excision was significantly higher in group B than in group A (93.3% versus 57.4%, p=0.0013). Post-operative complications, chemotherapy-associated side effects and local progressions were not increased in group B. Preoperative chemotherapy led to a decrease in the primary tumor size in all patients, 4/38 patients experiencing meanwhile a distant progression. The histological review of 19 matched tumor pairs (before and after chemotherapy) showed that proliferation was reduced and histological diagnosis feasible and accurate even after preoperative chemotherapy. The 5-year progression-free and overall survival rates were comparable between groups. Comparison of the longitudinal neuropsychological data showed that intellectual outcome tended to be better in group B (the mean predicted intellectual quotient value was 6 points higher throughout the follow-up).CONCLUSIONPreoperative chemotherapy is a safe and efficient strategy for metastatic medulloblastoma. It increases the rate of complete tumor excision and may improve the neuropsychological outcome without jeopardizing survival.

Immune factors associated with the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer

Immune activation plays an important role in achieving the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer. We evaluated how the immune response contributes to various therapeutic effects. This study was conducted on 43 patients with stages II–IV breast cancer who received preoperative chemotherapy followed by surgery. Peripheral natural killer (pNK) cell activity and the neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratio (PLR) were assessed before and after chemotherapy. Tumor-infiltrating lymphocytes (TILs) and levels of 14 tumor microenvironmental factors, analyzed by next-generation sequencing, were assessed in formalin-fixed, paraffin-embedded sections of preoperative biopsy samples and surgical specimens. Univariate analysis showed that grade 2 (G2) and better therapeutic effects were significantly associated with human epidermal growth factor receptor 2 (HER-2)-positive cancer, lower PLRs, and higher NK cell and interleukin-6 levels after chemotherapy. The disappearance of axillary lymph-node metastasis was significantly associated with HER-2-positive cancer; increased pNK cell activity and lower PLRs and vascular endothelial growth factor (VEGF) levels after chemotherapy; and increased cytotoxic T lymphocyte antigen 4 (CTLA-4) levels in regulatory T cells (Tregs) and ≥5% TILs before chemotherapy. Multivariate analysis showed that G2 and better therapeutic effects tended to be associated with higher NK cell levels after chemotherapy (odds ratio = 1.02; 95% confidence interval, 0.99–1.05; P = 0.07). The activation of local and systemic immune responses by downregulation of immunosuppressive factors, such as VEGF and CTLA-4 in Tregs, had variable pathological and therapeutic effects after preoperative chemotherapy in patients with breast cancer.

Lauren Classification Is A Predictor For Pathological Response Of Preoperative Chemoradiotherapy Compared With Preoperative Chemotherapy In Patients With Locally Advanced Gastric Cancer

To investigate the predictive value of Lauren classification to tumor pathological response after preoperative chemoradiotherapy (CRT) vs. preoperative chemotherapy (ChT) in locally advanced gastric adenocarcinoma (LAGC). From June 2013 to Dec, 2019, 182 patients in our hospital were enrolled into an ongoing multicentric phase III clinical trial comparing preoperative CRT (induction XELOX × 1 + 45Gy/25f with concurrent dose-reduced XELOX × 2) with preoperative ChT (XELOX × 3) in LAGC (NCT01815853). The clinical stage should be cT3N2-3M0, cT4aN+M0, or cT4bNanyM0. There were 124 males and 58 females, median age was 60 yrs (range 26-75 yrs). The interval between end of RT and surgery was 6-8 weeks. 65 out of 91 patients in the ChT group and 61 out of 91 patients in the CRT group had completed the preoperative treatments and the following radical D2 gastrectomy. Pathological response of primary tumor was categorized with NCCN tumor regression grade (TRG). Favorable pathological response (FPR) was defined as TRG0-1 with ypN0. At enrollment, patients’ baseline and tumor characteristics were well-balanced between the two groups. Proximal GC was in 58.2% (53/91) and 50.5(46/91) of the CRT and ChT group, respectively. Intestinal type (IT) GC was identified in 33(36.3%) patients of the ChT group, and in 36(39.6%) patients of the CRT group (X2 = 0.51, p = 0.916). After D2 gastrectomy, proportions of IT were 32.3% (21/65 pts) in the ChT group, and 50.8% (31/61 pts) in the CRT group, showing obvious shift towards resectability favoring IT vs. non-intestinal (n-IT, diffused plus mixed) type (X2 = 8.61, P = 0.035) after CRT. CRT group achieved higher rate of pCR (21.3% vs 3.1%, P = 0.002). There were 30, 37, and 22 patients obtained TRG0-1, ypN0, and FPR, respectively in the CRT group, while only 10, 14, and 5 patients did in the ChT group (P<0.001 for all). In the CRT group, ypN0 and FPR were observed in 80.6% and 45.2% of patients with IT tumor, but only in 35.7% and 21.4% with n-IT tumors (ypN0:P<0.001; FPR: P = 0.054), respectively. Logistic regression revealed IT tumor with higher probability of achieving ypN0 (OR = 7.500, 95%CI: 1.838-30.730; P = 0.005) than n-IT tumors. In contrast, no such differences were observed in the ChT group. Primary tumor locations were not predictive for ypN0 or TRG. In all patients with IT tumors, CRT was associated with higher rates of TRG0-1 (51.6% vs. 14.3%, P = 0.006), ypN0 (80.6% vs. 19.0%, P<0.001), FPR (45.2% vs. 0%, P<0.001) , pCR (22.6% vs. 0%, P = 0.033), and upstage 0-II (93.5% vs. 50.0%, P = 0.001) than ChT, while in patients with n-IT GC, only TRG showed significant improvement favoring CRT than ChT(TRG0-1: 42.9% vs. 15.9%, P = 0.011). Intestinal type gastric adenocarcinomas showed better responses to preoperative CRT vs. preoperative ChT than diffuse or mixed type GC did. This is the first set of data to date suggesting the predictive value of Lauren classification to tumor response after preoperative treatment in gastric cancer.

Combined treatment options for resectable common bile duct cancer patients

This article demonstrates a review of scientific works enlightened to combined treatment options for common bile duct cancer patients. The role of adjuvant therapy is highlighted. It has been shown that only capecitabine can be routinely prescribed in the postoperative period: median survival rate in general group of patients consisted 51 month versus 36 month in control group, ( p = 0.028). Neoadjuvant chemotherapy for common bile duct cancer patients is still less studied and the research works results are mostly negative. At present, preoperative chemotherapy for patients with primary resectable tumors should not be applied currently excepting the scientific research protocol boundaries. A new chemotherapy regimen including gemcitabine, cisplatine and nab-paclitaxel has appeared which demonstrates a partial response to therapy reaching 45% for the patients with unresectable biliary cancer. The data of the retrospective study showing the positive role of neoadjuvant radiotherapy combined with gemcitabine: 70% of patients had a partial response as well as reliable improvement of recurrence-free ( p = 0.0263) and overall ( p = 0.00187) survival rates was observed compared to the group of patients who had no neoadjuvant therapy. The necessity of search for new additional treatment options for the common bile duct cancer patients in preoperative and postoperative period leaves no doubt.

Transatlantic registries of pancreatic surgery in the United States of America, Germany, the Netherlands, and Sweden: Comparing design, variables, patients, treatment strategies, and outcomes

BackgroundRegistries of pancreatic surgery have become increasingly popular as they facilitate both quality improvement and clinical research. We aimed to compare registries for design, variables collected, patient characteristics, treatment strategies, clinical outcomes, and pathology. MethodsRegistered variables and outcomes of pancreatoduodenectomy (2014–2017) in 4 nationwide or multicenter pancreatic surgery registries from the United States of America (American College of Surgeons National Surgical Quality Improvement Program), Germany (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie - Studien-, Dokumentations- und Qualitätszentrum), the Netherlands (Dutch Pancreatic Cancer Audit), and Sweden (Swedish National Pancreatic and Periampullary Cancer Registry) were compared. A core registry set of 55 parameters was identified and evaluated using relative and absolute largest differences between extremes (smallest versus largest). ResultsOverall, 22,983 pancreatoduodenectomies were included (15,224, 3,558, 2,795, and 1,406 in the United States of America, Germany, the Netherlands, and Sweden). Design of the registries varied because 20 out of 55 (36.4%) core parameters were not available in 1 or more registries. Preoperative chemotherapy in patients with pancreatic ductal adenocarcinoma was administered in 27.6%, 4.9%, 7.0%, and 3.4% (relative largest difference 8.1, absolute largest difference 24.2%, P < .001). Minimally invasive surgery was performed in 7.8%, 4.5%, 13.5%, and unknown (relative largest difference 3.0, absolute largest difference 9.0%, P < .001). Median length of stay was 8.0, 16.0, 12.0, and 11.0 days (relative largest difference 2.0, absolute largest difference 8.0, P < .001). Reoperation was performed in 5.7%, 17.1%, 8.7%, and 11.2% (relative largest difference 3.0, absolute largest difference 11.4%, P < .001). In-hospital mortality was 1.3%, 4.7%, 3.6%, and 2.7% (relative largest difference 3.6, absolute largest difference 3.4%, P < .001). ConclusionConsiderable differences exist in the design, variables, patients, treatment strategies, and outcomes in 4 Western registries of pancreatic surgery. The absolute largest differences of 24.3% for the use of preoperative chemotherapy, 9.0% for minimally invasive surgery, 11.4% for reoperation rate, and 3.4% for in-hospital mortality require further study and improvement. This analysis provides 55 core parameters for pancreatic surgery registries.

Abstract 6498: Preoperative treatment remodels immune microenvironment via decreasing pro-tumorigenic and increasing anti-tumorigenic immune cells in the locally advanced gastric cancer

Abstract Purpose: To investigate the immune response in the tumor microenvironment and the association between immune response and pathological response after preoperative chemotherapy or preoperative chemoradiotherapy for locally advanced gastric cancer. Experimental Design:123 patients with locally advanced gastric cancer with or without preoperative treatment were analyzed by immunohistochemistry for CD4, CD45RO, FOXP3 and PD-L1. 83 of the 123 patients completed preoperative treatment and radical gastrectomy in our hospital between June 2013 and September 2019, which belonged to an ongoing multicentric randomized phase III clinical trial comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer (NCT01815853). They were 41 patients in the preoperative chemoradiotherapy (CRT) group, and 42 patients in the preoperative chemotherapy (ChT) group. The other 40 patients underwent surgery first without preoperative treatment (Surgery First group: SF) matched according to clinical pathological characteristics with the CRT and ChT group. T-cell subset densities both within tumor area and at the invasive front were analyzed using slide digital imaging and automated and software-based quantification algorithms. Pathological response of primary tumor was analyzed according to the NCCN tumor regression grade (TRG). The differences of T-cell subset densities and PD-L1 status among three groups and the relationship between these differences and tumor regression was evaluated. Results: The patients’ baseline and tumor characteristics were well-balanced among CRT, ChT, and SF groups. 28 patients obtained TRG0-2 in CRT group (n=41), in contrast, only 18 patients obtained TRG0-2 in ChT group (n=42; P=0.020). The number of FOXP3+ T cell and CD45RO+ T cell infiltrations was significantly lower in the CRT group (tumor area: P&amp;lt;0.001, P=0.011 respectively; invasive front: P&amp;lt;0.001, P&amp;lt;0.001 respectively) or ChT group (tumor area: P&amp;lt;0.001, P=0.033 respectively; invasive front: P&amp;lt;0.001, P=0.001 respectively) comparing with SF group. In contrast, the number of CD8+ T cells in tumor invasive front was significant higher in the CRT group (P&amp;lt;0.001) or ChT group (P=0.002) comparing with SF group. Addition of radiation to preoperative chemotherapy (CRT) significantly decreased PD-L1 expression in tumor cells (CRT group vs. ChT group: 14.6% vs. 35.7%, P=0.027). However, no differences of T cell infiltrations and PD-L1 expression in immune cells between CRT group and ChT group were observed. In CRT group, lower FOXP3+ cell density in tumor area (P&amp;lt;0.001) and invasive front (P=0.009), higher CD8+ cell density (P=0.040) and CD45RO+ T cell density (P=0.045) in tumor area were strongly associated with higher probability of achieving TRG0-2. In ChT group, lower FOXP3+ cell density in tumor area (P=0.027) and higher CD8+ cell density (P=0.040) in invasive front were significantly associated with higher probability of achieving TRG0-2. Conclusions: Preoperative treatment in locally advanced gastric cancer is useful for reducing regulatory T cell levels and increasing cytotoxic T cell levels. CRT and ChT may not only be cytotoxic, but have pleiotropic and beneficial effects on the tumor microenvironment. Citation Format: Yi Fang, Yujing Zhang, Nai Li, Yihong Ling, Zhiwei Zhou. Preoperative treatment remodels immune microenvironment via decreasing pro-tumorigenic and increasing anti-tumorigenic immune cells in the locally advanced gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6498.

Venous thromboembolism during preoperative chemotherapy in the CRITICS gastric cancer trial.

BackgroundThe occurrence of a venous thromboembolism (VTE) is common in patients with cancer. Gastric cancer has been associated with one of the highest risks for VTE. Chemotherapy, especially cisplatin has been associated with a high VTE risk. In this study, risk factors for VTE occurrence and their potential impact on subsequent therapeutic interventions were investigated in patients who underwent preoperative chemotherapy, in the CRITICS gastric cancer trial.Patients and methodsPatients with resectable gastric cancer were preoperatively treated with three cycles of 3‐weekly epirubicin, cisplatin or oxaliplatin, and capecitabine (ECC/EOC). VTE was defined as any thrombus in the venous system, excluding superficial and/or device related VTEs. Potential risk factors were analyzed in a multivariable regression model with age, gender, Body Mass Index (BMI), tumor localization, Lauren classification, type of chemotherapy (ECC/EOC), (cardiovascular) comorbidity, and previous VTE as independent risk factors. The impact of VTE on completion rate of preoperative chemotherapy, surgical resection rate, postoperative complications, and start of postoperative therapy were investigated.ResultsOf 781 patients, 78 (10%) of 781 patients developed a VTE during preoperative chemotherapy. On multivariable analysis, BMI ≥ 30 kg/m2 and previous VTE were associated with VTE occurrence (reference BMI < 25 kg/m2; OR 2.190; 95% CI 1.152‐4.164; P = .017/previous VTE; OR 3.617; 95% CI 1.201‐10.890; P = .022). Treatment with cisplatin was, compared to oxaliplatin, not significantly associated with VTE occurrence (OR 1.535; 95% CI 0.761‐3.094; P = .231). VTE occurrence did not affect completion of preoperative chemotherapy, surgical resection rate, postoperative complications, or start of postoperative therapy.ConclusionHigh BMI and previous VTE were independent risk factors for VTE occurrence during preoperative chemotherapy in patients with resectable gastric cancer. VTE occurrence in the preoperative setting did not affect receipt of further treatment.

How to Prevent Sarcopenia Occurrence during Neoadjuvant Chemotherapy for Oesogastric Adenocarcinoma?

The aim of this study was to evaluate the impact of a preoperative feeding jejunostomy (FJ) on the occurrence of sarcopenia before and after preoperative chemotherapy for patients with an oesogastric adenocarcinoma (OGA). Forty-six patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. Sarcopenia was evaluated by measuring muscle surfaces (psoas, paraspinal and abdominal wall muscles) on abdominal CT images at the level of the 3rd lumbar vertebra. A FJ was placed in 31 patients (67.4%) before the neoadjuvant treatment (FJ group), while 15 patients (32.6%) started neoadjuvant treatments without FJ (control group). After preoperative chemotherapy, there were significantly more sarcopenic patients in the control group, compared to the FJ group. In the FJ group, 13% of the patients (n = 4) were sarcopenic before treatment and 22.6% of them (n = 7) became sarcopenic after preoperative chemotherapy (p = 0.3). In the control group, if initially only 6.7% (n = 1) of patients were sarcopenic, the majority of the patients (60%, n = 9) became sarcopenic after chemotherapy (p = 0.012). The FJ was an independent risk factor of sarcopenia after neoadjuvant chemotherapy. FJ with enteral nutritional support during the preoperative management of OGA seemed to efficiently counteract sarcopenia occurrence during preoperative chemotherapy.

Role of neoadjuvant chemotherapy in metastatic medulloblastoma: a comparative study in 92 children.

BackgroundPrevious pilot studies have shown the feasibility of preoperative chemotherapy in patients with medulloblastoma, but benefits and risks compared with initial surgery have not been assessed.MethodsTwo therapeutic strategies were retrospectively compared in 92 patients with metastatic medulloblastoma treated at Gustave Roussy between 2002 and 2015: surgery at diagnosis (n = 54, group A) and surgery delayed after carboplatin and etoposide-based neoadjuvant therapy (n = 38, group B). Treatment strategies were similar in both groups.ResultsThe rate of complete tumor excision was significantly higher in group B than in group A (93.3% vs 57.4%, P = 0.0013). Postoperative complications, chemotherapy-associated side effects, and local progressions were not increased in group B. Neoadjuvant chemotherapy led to a decrease in the primary tumor size in all patients; meanwhile 4/38 patients experienced a distant progression. The histological review of 19 matched tumor pairs (before and after chemotherapy) showed that proliferation was reduced and histological diagnosis feasible and accurate even after neoadjuvant chemotherapy. The 5-year progression-free and overall survival rates were comparable between groups. Comparison of the longitudinal neuropsychological data showed that intellectual outcome tended to be better in group B (the mean predicted intellectual quotient value was 6 points higher throughout the follow-up).Conclusion Preoperative chemotherapy is a safe and efficient strategy for metastatic medulloblastoma. It increases the rate of complete tumor excision and may improve the neuropsychological outcome without jeopardizing survival.Key Points1. Preoperative chemotherapy increases the rate of complete tumor removal.2. No additional risk (toxic or disease progression) is linked to the delayed surgery.3. Preoperative chemotherapy could have a positive impact on the neuropsychological outcome of patients.

RESULTS OF COMBINED MODALITY TREATMENT WITH PREOPERATIVE CHEMOTHERAPY IN ESOPHAGEAL CANCER PATIENTS

The purpose of the study: to analyze the efficacy of combined modality treatment including preoperative chemotherapy with gemcitabine/cisplatin in patients with stage II-III esophageal cancer (EC). Materials and methods: The study included 70 patients with stage II-III EC, who were treated at the Cancer Research Institute (Tomsk, Russia) from 2012 to 2019. The patients were divided into 2 groups. Group I comprised 35 patients, who received 2 cycles of preoperative chemotherapy with gem-citabine (1250 mg/m2 on days 1 and 8) and cisplatin (80 mg/ m2 on day 1) followed by radical surgery. Group II included 35 patients who underwent surgery alone. All patients underwent subtotal resection of the esophagus with simultaneous esophageal reconstruction using gastric tube (68.6%) or colon tissue (31.4%). Results: The overall tumor response to preoperative chemotherapy according to RECIST 1.1 criteria was 57.1%, including complete response (5.7%) and partial response (51.4%). No severe complications were observed. R0 resection was achieved in all patients (100%). No difference in the rate of postoperative complications between Group I and Group II was found (34.3% and 40%, respectively). There was no statistically significant difference in the mortality rate between treatment groups (8.6% versus 57%) (p&gt;0.05). Pathological complete tumor response was 5.7%. In Group I patients, the 2-year disease-free and overall survival rates were 71.8% and 81.3%, respectively. The corresponding values in Group II patients were 39.4% and 51.5%, respectively (p=0.01). Conclusion: Preoperative chemotherapy for patients with stage II-III EC demonstrated high response rates, having no adverse effect on the perioperative period and mortality. The 2-year survival rates were significantly higher in patients, who received combined modality treatment with preoperative chemotherapy than in patients, who underwent surgery alone.

Abstract P5-04-10: Immune and transcriptional signatures of dendritic cell (DC) vaccination combined with chemotherapy in locally advanced, triple-negative breast cancer (TNBC) patients

Abstract Women with triple-negative breast cancer (TNBC) have an increased pathologic complete response rate (pCR; residual disease after neoadjuvant chemotherapy) as compared to women with non-TNBC, and those with pCR have a 90% disease-free survival. However, women with TNBC who do not achieve a pCR have an increased risk of recurrence, decreased overall survival, and post-recurrence survival as compared to women with non-TNBC who do not achieve a pCR. A high priority for clinical research is therefore to increase the pCR rate in breast and axilla with preoperative therapy, as therapeutic options for patients who do not have a pCR are limited. Immunotherapy is an attractive strategy as human BCs can be immunogenic and enhancing the immune effector function may augment the cytotoxic effects of standard therapies. Immunity against tumor antigens can be boosted in cancer patients by vaccination with ex vivo-generated tumor antigen-loaded DCs. Here, we report the extended analysis of a clinical trial on 10 TNBC pts assessing the feasibility of combining cyclin B1/WT1/CEF (antigen)-loaded DC vaccination with preoperative chemotherapy in patients with locally advanced TNBC. Combination of preoperative chemotherapy and intratumoral and subcutaneous autologous DC vaccination led to 70% of combined rate of pCR and residual cancer burden 1 (RCB1). To assess expansion of antigen-specific T cell responses, IFN-g-ELISpot was carried out with PBMCs from baseline (BL) and several time points during vaccine treatment that were cultured with control peptides or with peptide libraries covering vaccine antigens. The expansion of antigen-specific immune responses could be detected at various time points post treatment. Transciptional profiling on blood (Nanostring) and tumors (RNAseq) revealed profound changes in immune transcription signatures. T cell and DC signatures in blood and T cell, inflammation, cytotoxic and cell cycle signatures in pre-chemotherapy breast cancer biopsies were linked with pathological responses in definitive surgery specimens. Taken together, differential gene and immunologic signatures of the pre-treatment breast cancer biopsies distinguish pts who have a pCR vs no pCR and can identify potential therapeutic targets for pts with TNBC. Citation Format: Te-Chia Wu, Joyce O’Shaughnessy, Lee K. Roberts, Jennifer L. Smith, Susan B. Burkeholder, Jennifer Finholt, Jessica Tarnowski, Tuoc Dao, Jeffrey Lamont, Sandra M. Zurawski, Phuong Nguyen, Yuanyuan Wang, Kyung In Kim, Derek Blankenship, Jacob Turner, Xuan Wang, Florentina Marches, Maren K. Levin, Michael Grant, Gerard Zurawski, Virginia Pascual, Jacques Banchereau, Karolina Palucka. Immune and transcriptional signatures of dendritic cell (DC) vaccination combined with chemotherapy in locally advanced, triple-negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-10.

Immune Response Assessed by Flow-Cytometry and Immunhistochemistry is Linked to Pathological Response after Preoperative Chemotherapy in Patients Undergoing Resection for Colorectal Liver Metastases

Background: Preoperative chemotherapy followed by curative-intent resection represents the mainstay in treatment of advanced colorectal cancer liver metastases (CRCLM). The host immune response classified by the presence of tumour-infiltrating lymphocytes (TILS) has been verified as a major contributor to oncological outcome in several malignant diseases including colorectal cancer. This study characterizes the immune cell distribution in different tumour compartments by flow cytometry and immunohistochemistry to establish a link between immune response and pathological tumour regression grading (TRG) in patients undergoing liver resection for CRCLM.

Efficacy of Preoperative Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

The impact of preoperative chemotherapy in patients with upper urinary tract urothelial carcinoma remains poorly investigated. We assessed the rates of pathological complete response (pT0N0/X) and downstaging (pT1N0/X or less) at radical nephroureterectomy after preoperative chemotherapy and evaluated their impact on survival. This was an international observational study of patients who underwent preoperative chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma between 2005 and 2017. Multiple imputation of chained equations was applied to account for missing values. Logistic regression analyses were performed to identify predictors of pathological response. Cox proportional hazard regression models were used to estimate recurrence-free survival, cancer specific survival and overall survival. A total of 267 patients met our inclusion criteria. Among included patients 82 (31%) received methotrexate, vinblastine, doxorubicin and cisplatin; 123 (46%) gemcitabine and cisplatin; 25 (9%) gemcitabine and carboplatin; and 32 (12%) other regimens. The overall rates of pathological complete response and pathological downstaging were 10.1% and 44.9%, respectively. On multivariable analysis the use of gemcitabine and cisplatin, and gemcitabine and carboplatin was not statistically different from methotrexate, vinblastine, doxorubicin and cisplatin in achieving pathological complete response and pathological downstaging, respectively. The number of administered cycles did not appear to have an effect on pathological responses. Pathological downstaging was the strongest prognostic factor for recurrence-free survival (HR 0.2, p <0.001), cancer specific survival (HR 0.19, p <0.001) and overall survival (HR 0.40, p <0.001). Pathological downstaging after preoperative chemotherapy is a robust prognostic factor at radical nephroureterectomy and is associated with improved survival outcomes. Although preoperative chemotherapy appears to be effective, well designed prospective studies are still needed.

Three-phase scintigraphy in evaluation of preoperative chemotherapy of soft tissue sarcomas of extremities

Purpose. To determine the diagnostic value of threephase scintigraphy in the evaluation of the preoperative chemotherapy of soft tissue sarcomas of the extremities on different diagnostic stages. Material and methods. We analyzed the data of 76 patients with extremity soft tissue sarcomas. The study included data from 28 patients who underwent three-phase scintigraphy with Technetril 99mTc. Scintigraphic data before and after neoadjuvation chemotherapy were analyzed in 16 patients, before and during chemotherapy — in 6 patients, only during chemotherapy — in 1 and only after all courses of chemotherapy — in 5 patients. Results. The sensitivity of the method (prediction of grade III–IV pathologic response) was 100 %, specificity (prediction of grade I–II pathologic response) was 87%. The predictive value of positive and negative results was 63 and 100%, respectively. Conclusion. A three-phase scintigraphy with Technetril 99mTc is a highly informative method for evaluating the effectiveness of preoperative chemotherapy in patients with sarcomas of soft tissues of the extremities.

Low Total Pathologic Complete Response (tpCR) Rate to Preoperative Chemotherapy in Patients with Invasive Lobular Carcinoma of Breast (ILC): Analysis of Subgroup of Three Phase II Trials

Low Total Pathologic Complete Response (tpCR) Rate to Preoperative Chemotherapy in Patients with Invasive Lobular Carcinoma of Breast (ILC): Analysis of Subgroup of Three Phase II Trials

Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT

BackgroundThe prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.MethodsEligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy.DiscussionThe results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.Trial registrationClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

Pre- or postoperative chemotherapy in patients with colorectal cancer with synchronous, resectable liver metastases?

At the moment, there is no clear scientific data on the use of preoperative chemotherapy in patients with colorectal, synchronous, resectable liver metastases. Below arguments are presented against the use of preoperative chemotherapy in the above clinical situation, based on an analysis of three issues: the toxicity of preoperative chemotherapy and associated perioperative complications, the efficacy of pre- and postoperative chemotherapy, doubts related to the use of preoperative chemotherapy. To summarise, most scientific data is against preoperative chemotherapy as it causes significant adverse effects (hepatotoxicity and consequent postoperative complications) without a significant improvement in survival rates. Therefore, postoperative chemotherapy in this group of patients seems to be the more optimal treatment.

A potential role for peripheral natural killer cell activity induced by preoperative chemotherapy in breast cancer patients.

Tumor-infiltrating lymphocytes are an important prognostic factor after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Natural killer (NK) cells play critical roles in antitumor immune surveillance. Here, we assessed the relationship between peripheral natural killer (pNK) cell activity, tumor microenvironmental factors (TMEFs), and the therapeutic efficacy of preoperative chemotherapy in patients with breast cancer. In a cohort of 39 patients diagnosed with stage II-IV breast cancer who received NAC, we measured pNK cell activity by chromium release assay and assessed TMEF levels by next-generation sequencing. Following NAC, pNK cell activity was increased in 24/39 patients but decreased in 15/39 patients. Increased pNK cell activity following preoperative chemotherapy was associated significantly with the disappearance of axillary lymph node metastasis (Ax+; p = 0.0235). Increased pNK cell activity remained significantly associated with the disappearance of Ax+ in multivariate logistic regression analysis (OR 5.41, 95% CI 1.19-24.52, p = 0.0283). A Grade 2 or higher effect of NAC was associated with high pre-NAC cytotoxic T lymphocyte-associated protein 4 (CTLA-4) levels (p = 0.0281) and elevated post-NAC NK (p = 0.0005) cells and transforming growth factor-beta (TGF-β; p = 0.0350) levels. The disappearance of Ax+ was associated with high pre-NAC CTLA-4 levels (p = 0.0278) and elevated CD4 levels after NAC (p = 0.0250). The systemic activation of pNK cells after NAC may improve metastatic tumor elimination in patients with breast cancer owing to a release from local immunosuppression, and immune activation in the tumor microenvironment.

The long-term prognostic difference between gastrectomy with and without preoperative chemotherapy in patients with clinical stage IV gastric cancer

The role of gastrectomy for stage IV gastric cancer (GC) has not yet been established. Thus, we aimed to compare the prognoses of patients with clinical stage IV GC who underwentgastrectomy with and without preoperative chemotherapy after precise recategorization of patients. We retrospectively reviewed a total of 92 clinical stage IV GC patients who underwent gastrectomy with or without preoperative chemotherapy between 2010 and 2016 at a single institution. Yoshida's classification was used to categorize the patients intothe following categories: 1, technically resectable metastasis; 2, marginally resectable metastasis; 3, unresectable peritoneal dissemination; and 4, incurable peritoneal dissemination with distant organ metastasis. Two-year disease-specific survival (DSS) rates were compared between patients who underwent primary surgery and preoperative chemotherapy for each category. The two-year DSS rates of primary surgery vs. preoperative chemotherapy in Categories 1, 2, 3, and 4 (n=35, 39, 14, and 4, respectively) were 48.6% vs. 41.7% (p=0.829), 52.6% vs. 40.0% (p=0.855), 50.0% vs. 75.0%(p=0.027), and 0% vs. 66.7% (p=0.083), respectively. Patients in Categories 1 and 2 who underwent preoperative chemotherapy tended to have lower two-year DSS rates (p=0.911), whereas patients in Categories 3 and 4 had significantly higher two-year DSS rates than those who underwent primary surgery (p=0.014). Primary surgery may be performed in patients without peritoneal dissemination when GC is technically resectable. However, if peritoneal dissemination is suspected, chemotherapy should be prioritized.

Low total pathologic complete response rate to preoperative chemotherapy in patients with invasive lobular carcinomaof the breast.

IntroductionTotal pathologic complete response (tpCR; ypT0/is ypN0) after preoperative chemotherapy (PCT) is associated with better outcome in locally advanced breast cancers. However, the tpCR rate according to histology is not usually considered in trials.Material and methodsPatients with invasive lobular breast carcinoma (ILC), who were included in three phase II trials (AT, ATX, and TXH), were eligible. Expression of markers and clinical phenotypes (CPh) were determined by immunohistochemistry. The primary endpoint was tpCR rate in patients with ILC. Secondary endpoints were breast-conserving surgery rate (BCSR), event-free survival (EFS), and overall survival (OS).ResultsIn the subgroup of patients with ILC (n = 16) the median age was 50 years, 56.25% were premenopausal, median tumour size was 5 cm, and 68.75% had clinically node involvement. Six patients (37.5%) had clinical stage II, and 10 (62.5%) had clinical stage III. Hormone receptor-positive disease was present in 93.75% of the patients, and median Ki-67 was 25%. CPh were Luminal A-like in 37.5%, Luminal B-like in 50%, HER2-positive in 6.25%, and triple negative in 6.25% of tumours. Only one patient (6.25%) had a tpCR, and another patient had a pathologic complete response (pCR) only in the breast. With a median follow-up of 146 months, median EFS was 120 months (95% CI: 68–139), and median OS was not reached. Ten-year EFS and OS probability were 47% and 60%, respectively. BCSR was only 12.5%.ConclusionsPCT in patients with ILC is associated with low tpCR rate because the majority of these patients have Luminal tumours with low chemo-sensitivity.