Preoperative Systemic Treatment Research Articles

Comparison of outcomes between preoperative and postoperative systemic treatment in patients with hepatocellular carcinoma: a SEER database-based study.

Significant advancements in systemic treatment for hepatocellular carcinoma have been made in recent years. However, the optimal timing of systemic treatment before or after surgery remains unknown. This study aims to evaluate the impact of sequencing systemic treatment and surgical intervention on the long-term prognosis of hepatocellular carcinoma patients. In our study, we analyzed data from patients diagnosed with primary liver cancer (2004-2015) extracted from the SEER database. Patients who underwent both systemic treatment and surgical intervention were selected, divided into preoperative and postoperative systemic therapy groups. The primary endpoint of the study is overall survival(OS), and the secondary endpoint is cancer-specific survival (CSS). Propensity score matching (PSM) reduced the influence of confounding factors, while Kaplan-Meier curves and a multivariable Cox proportional hazards model accounted for variables during survival analysis. A total of 1918 eligible HCC patients were included, with 1406 cases in the preoperative systemic treatment group and 512 cases in the postoperative systemic treatment group. Survival analysis showed that both the preoperative group demonstrated longer median overall survival (OS) and median cancer-specific survival (CSS) before and after PSM. After conducting multivariate COX regression analysis with stepwise adjustment of input variables, the postoperative systemic treatment group continued to exhibit a higher risk of all-cause mortality (HR: 1.84, 95% CI: 1.55-2.1) and cancer-specific mortality (HR: 2.10, 95% CI: 1.73-2.54). Subgroup analysis indicated consistent results for overall survival (OS) across different subgroups. Hepatocellular carcinoma patients from the SEER database who received preoperative systemic therapy had superior OS and CSS compared to those who received postoperative systemic therapy.

Benefit of postoperative regional nodal irradiation in patients receiving preoperative systemic therapy with docetaxel/carboplatin/trastuzumab/pertuzumab for HER2-positive breast cancer

AimThe role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. MethodsWe retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. ResultsThe RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. ConclusionWith a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

Predictive Factors for the Survival Outcomes of Preoperative Chemotherapy in Patients with Resectable and Borderline Resectable Colorectal Cancer with Liver Metastasis.

Preoperative chemotherapy increases resectability in borderline resectable colorectal liver metastasis (CRLM) patients who undergo curative liver surgery. Most clinical risk scores and other predictive factors for survival have been extensively studied in patients who undergo upfront liver surgery. However, predictive factors of CRLM patients who received preoperative chemotherapy remains controversial. CRLM patients who received preoperative systemic therapy followed by curative liver surgery at our institution between 1/2012 and 12/2018 were included. This study aimed to investigate factors that predicted the outcomes of preoperative systemic treatment, optimal dose/duration, and toxicity in patients with CRLM. Ninety-eight patients were eligible for analysis. Most patients received oxaliplatin-based chemotherapy (72.7%), while 15.9% received both oxaliplatin and irinotecan. Biologic agents were administered in 48.9% of patients. Overall, chemotherapy-induced liver injury was observed in 38.5%. The median disease-free survival (DFS) and overall survival (OS) were 8.7 months and 3.6 years, respectively. Baseline, pre-surgery, and increased Fong scores after preoperative chemotherapy were significantly associated with DFS and OS. In multivariate analysis, a high Fong score at baseline (p=0.018) was significantly associated with shorter DFS, whereas male sex (p=0.040) and liver surgery (p=0.044) were related to longer OS. In our study, Fong clinical risk scores, female sex, and liver surgery as a part of liver-directed therapy were independent prognostic factors for survival in CRLM patients who received preoperative chemotherapy. These clinical factors should be considered as an option to guide physicians' decisions in selecting patients with CRLM who may benefit most from curative liver-directed therapy.

Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer-A Literature Review.

The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15-20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in approximately 15% of cases. The neoadjuvant approach has multiple benefits that include the potential to downgrade staging and convert previously unresectable tumors to operable tumors. In addition, achieving a pathologic complete response (pCR) following preoperative systemic treatment is prognostic of enhanced survival outcomes. Thus, optimal evaluation among the suitable strategies is crucial in deciding which patients should be selected for the neoadjuvant approach. A literature search was conducted in the Embase, Medline, and Cochrane electronic libraries. The evaluation of tumor and LN staging and, hence, stratifying BC recurrence risk are decisive factors in guiding clinicians to optimize treatment decisions between the neoadjuvant versus adjuvant approaches. For each individual case, it is important to consider the most likely postsurgical outcome, since, if the patient does not obtain pCR following neoadjuvant treatment, they are eligible for adjuvant T-DM1 in the case of residual disease. This review of HER2-positive female BC outlines suitable neoadjuvant and adjuvant systemic treatment strategies for guiding clinical decision making around the selection of an appropriate therapy.

Copy Number Variation in Inflammatory Breast Cancer.

Identification of a unique genomic biomarker in de novo inflammatory breast cancer (IBC) may provide an insight into the biology of this aggressive disease. The goal of our study was to elucidate biomarkers associated with IBC. We examined breast biopsies collected from Dana-Farber Cancer Institute patients with IBC prior to initiating preoperative systemic treatment (30 samples were examined, of which 14 were eligible). Patients without available biopsies (n = 1), with insufficient tumor epithelial cells (n = 10), or insufficient DNA yield (n = 5) were excluded from the analysis. Molecular subtype and tumor grade were abstracted from a medical records' review. Ten IBC tumors were estrogen-receptor-positive (ER+) and human epidermal growth factor receptor 2 (HER2)-negative (n = 10 out of 14). Sufficient RNA and DNA were simultaneously extracted from 14 biopsy specimens using the Qiagen AllPrep Kit. RNA was amplified using the Sensation kit and profiled using the Affymetrix Human Transcriptome Array 2.0. DNA was profiled for genome-wide copy number variation (CNV) using the Affymetrix OncoScan Array and analyzed using the Nexus Chromosome Analysis Suite. Among the 14 eligible samples, we first confirmed biological concordance and quality control metrics using replicates and gene expression data. Second, we examined CNVs and gene expression change by IBC subtype. We identified significant CNVs in IBC patients after adjusting for multiple comparisons. Next, to assess whether the CNVs were unique to IBC, we compared the IBC CNV data to fresh-frozen non-IBC CNV data from The Cancer Genome Atlas (n = 388). On chromosome 7p11.2, we identified significant CN gain located at position 58,019,983-58,025,423 in 8 ER+ IBC samples compared to 338 non-IBC ER+ samples (region length: 5440 bp gain and 69,039 bp, False Discovery Rate (FDR) p-value = 3.12 × 10-10) and at position 57,950,944-58,025,423 in 3 TN-IBC samples compared to 50 non-IBC TN samples (74,479 base pair, gain, FDR p-value = 4.27 × 10-5; near the EGFR gene). We also observed significant CN loss on chromosome 21, located at position 9,648,315-9,764,385 (p-value = 4.27 × 10-5). Secondarily, differential gene expression in IBC patients with 7p11.2 CN gain compared to SUM149 were explored after FDR correction for multiple testing (p-value = 0.0016), but the results should be interpreted with caution due to the small sample size. Finally, the data presented are hypothesis-generating. Validation of CNVs that contribute to the unique presentation and biological features associated with IBC in larger datasets may lead to the optimization of treatment strategies.

Programmed death ligand 1-positive immune cells in primary tumor or metastatic axillary lymph nodes can predict prognosis of triple-negative breast cancer even when present at < 1% in the tumor region

BackgroundThe efficacy of pre-operative systemic treatment (PST) combined with immune checkpoint inhibition (ICI) for triple-negative breast cancer (TNBC) has been recognized recently as being independent of the degree of programmed death ligand-1 (PD-L1) positivity of infiltrating immune cells, especially for patients with axillary lymph node metastasis (ALNM).MethodsTNBC patients with ALNM were treated surgically between 2002 and 2016 in our facility (n = 109), of whom 38 received PST before resection. The presence of tumor-infiltrating lymphocytes (TILs) expressing CD3, CD8, CD68, PD-L1 (detected by antibody SP142) and FOXP3 at primary and metastatic LN sites was quantified.ResultsThe size of invasive tumor and the number of metastatic axillary LN were confirmed as prognostic markers. The numbers of both CD8+ and FOXP3+ TILs at primary sites were also recognized as prognostic markers, especially for overall survival (OS) (CD8, p = 0.026; FOXP3, p < 0.001). The presence of CD8+, FOXP3+ and PD-L1+ cells was better maintained in LN after PST and may contribute to improved antitumor immunity. Provided they were present as clusters of ≥ 70 positive cells, even < 1% of immune cells expressing PD-L1 at primary sites predicted a more favorable prognosis for both disease-free survival (DFS) (p = 0.004) and OS (p = 0.020). This was the case not only for 30 matched surgical patients, but also in all 71 surgical only patients (DFS: p < 0.001 and OS: p = 0.002).ConclusionsPD-L1+ , CD8+ or FOXP3+ immune cells in the tumor microenvironment (TME) at both primary and metastatic sites are significant on prognosis, which could be a clue to expect the potential for better responses to the combination of chemotherapy and ICI, especially for patients with ALNM.

Abstract P2-11-30: Performance of tumor vascularity as a biomarker is correlated with the change of tumor vascularity after preoperative systemic treatment in patients with breast cancer

Abstract Background) Breast cancer is a leading cause of death worldwide. Tumor vascularity is a hallmark of cancer including breast cancer. However, targeting tumor vascularity did not show consistent benefit when applied in clinic. This study aimed to investigate in which group of patients can tumor vascularity be a prognostic factor and how does change of tumor vascularity play in this situation. Materials and methods) Female patients with breast cancer who received preoperative chemotherapy due to breast cancer between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. Clinocopathological characteristics were collected. Hounsfield units(HU) on contrast-enhanced computed tomography(CT) was used as a marker indicating tumor vascularity. Tumor to aortic arch ratio(TAR) of HU on contrast enhanced CT was applied to enhance objectivity of measurement. Patients were categorized according to the cut-off values retrieved from the receiver operating characteristic curve. Kaplan-Meier curves were generated to compare recurrence-free interval (RFI) and overall survival (OS). Results) The final cohort included 162 patients with a mean age of 48.63±7.9 (30-69) years. Initial TAR was 0.38±0.103 (range, 0.184-0.946) and TAR after completion of preoperative systemic treatment was 0.29 0.094(0.677-0.298). Difference between TAR of immediate before surgery and first clinical presentation was -0.0860.094(-0.386 – 0.176). TAR was decreased in 122 (75.3%) patients. Initial TAR was significantly correlated with recurrence free survival(RFS)(p=0.002). However, TAR after preoperative systemic treatment (p=0.221) or delta TAR (area under receiver operating characteristics = 0.498) were not significant. Interestingly, initial TAR was significant only in patients with decreased TAR after preoperative systemic treatment(p=0.005). Conclusion) Tumor vascularity represented with HU was significantly related with patients’ survival only when tumor vascularity was decreased in response to systemic treatment. Considering no antiangiogenic agents were applied as preoperative systemic treatment and still capacity of tumor vascularity as a biomarker was influenced by the change of itself, antiangiogenic agents could be used as a complimentary agent for the other agents which also impact tumor vascularity. Citation Format: Hyang Suk Choi, Eun Ju Son, Hany Hany Noh, In-Jeong Cho In-Jeong Cho, Seung Taek Lim, Jong-In Lee, Airi Han. Performance of tumor vascularity as a biomarker is correlated with the change of tumor vascularity after preoperative systemic treatment in patients with breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-30.

The role of anthracycline and pertuzumab in preoperative treatment of HER2-positive breast cancer

Polychemotherapy combined with trastuzumab (T) or trastuzumab with pertuzumab (TP) is a standard preoperative systemic treatment in patients with HER2-positive breast cancer. In Poland T is reimbursed according to the Drug Prescription Program of Ministry of Health (MoH) for patients with primary breast tumors bigger than 1cm independently from nodal status, whereas TP is reimbursed for patients with tumors bigger than 2 cm with positive lymph node(s) or lack of hormonal receptors expression. The Drug Prescription Program does not indicate which polychemotherapy should be combined with anti-HER2 therapy. Therefore, one can choose between classical sequential treatment based on anthracycline and taxane combined with T or dual HER2 blockade (usually 4 × AC → 12 × paclitaxel/4 × docetaxel + T/TP), or docetaxel with carboplatin combined with trastuzumab (TCH) or with dual HER2 blockade (TCHP). According to the present guidelines of the National Comprehensive Cancer Network (NCCN), polychemotherapy without anthracycline is preferred, which is justified because of its lower toxicity, especially cardiotoxicity. Currently, a pathologically confirmed complete response (pCR) is usually the primary objective in clinical trials dedicated to preoperative systemic treatment in breast cancer. pCR became a surrogate of treatment effectiveness. That is why oncologists eagerly use polychemotherapy combined with dual HER2 blockade as preoperative treatment to increase the patient’s chance to achieve pCR, sometimes even when the patient’s risk of relapse is relatively small. The goal of this article is to review current evidence-based knowledge about the effectiveness and toxicity of polychemotherapy with or without anthracycline combined with trastuzumab or dual HER2 blockade used as preoperative treatment in HER2-positive breast cancer patients.

Normalization of tumor markers and a clear resection margin affect progression-free survival of patients with unresectable pancreatic cancer who have undergone conversion surgery

BackgroundWith the advent of intensive combination regimens, an increasing number of patients with unresectable pancreatic cancer (UPC) have regained the opportunity for surgery. We investigated the clinical benefits and prognostic factors of conversion surgery (CS) in UPC patients.MethodsWe retrospectively enrolled patients with UPC who had received CS following first-line systemic treatment in our center between 2014 to 2022. Treatment response, safety of the surgical procedure and clinicopathological data were collected. We analyzed the prognostic factors for postoperative survival among UPC patients who had CS.ResultsSixty-seven patients with UPC were enrolled (53 with locally advanced pancreatic cancer (LAPC) and 14 with metastatic pancreatic cancer (MPC)). The duration of preoperative systemic treatment was 4.17 months for LAPC patients and 6.52 months for MPC patients. All patients experienced a partial response (PR) or had stable disease (SD) preoperatively according to imaging. Tumor resection was unsuccessful in four patients and, finally, R0 resection was obtained in 81% of cases. Downstaging was determined pathologically in 87% of cases; four patients achieved a complete pathological response. Median postoperative-progression-free survival (PO-PFS) was 9.77 months and postoperative overall survival (PO-OS) was 31.2 months. Multivariate logistic regression analyses revealed that the resection margin and postoperative changes in levels of tumor markers were significant prognostic factors for PO-PFS. No factors were associated significantly with PO-OS according to multivariate analyses.ConclusionsCS is a promising strategy for improving the prognosis of UPC patients. The resection margin and postoperative change in levels of tumor markers are the most important prognostic factors for prolonged PFS. Multidisciplinary treatment in high-volume centers is strongly recommended. Prospective studies must be undertaken to resolve the various problems regarding optimal regimens, the duration of treatment, and detailed criteria for CS.

RAS Mutation Status Should Not Be Used to Predict Outcome from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases

BackgroundGenetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT).Patients and MethodsRetrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004–2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan–Meier curves were used to determine overall survival.ResultsOne hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4–184.9 months) and median OS was 38.7 months (95% CI 32.4–44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402–16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995–2.843, p = 0.052).ConclusionsRAS mutation status should not in isolation be used to select patients for CRS/HIPEC.

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis.

Simple SummaryThe features of preoperative systemic anticancer therapy associated with best outcomes after resection of initially-irresectable liver metastases from colorectal cancer are yet to be identified. We harnessed data from a prospective international surgical database (LiverMetSurvey) to explore the duration and modalities of preoperative systemic anticancer therapy associated with longer overall survival in this clinical setting. Our study included 2793 patients having undergone liver surgery after preoperative systemic anticancer treatment for initially irresectable disease. We found that short (<7 or <13 cycles in 1st or 2nd line, respectively) duration was associated with longer survival outcomes, independently from other prognostic factors. Conversely, all the comparisons between different conventional active regimens displayed similar results. Our findings support the recommended onco-surgical approach of aiming at performing liver surgery as soon as technically feasible after response to preoperative systemic anticancer therapy in hepatic metastases from colorectal cancer, initially not amenable to surgery. The results of this study also suggest that, provided the systemic anticancer therapy regimen is active, the choice of the drugs used bears overall little if any impact on the outcomes. Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.

Treatment response and 5-year distant metastasis-free survival outcome in breast cancer patients after the use of MammaPrint and BluePrint to guide preoperative systemic treatment decisions

AimIn the prospective neoadjuvant NBREaST II study, we measured the response to preoperative treatment and 5-year survival outcome in the molecular subgroups as determined by combining the MammaPrint and BluePrint. MethodsBetween 2012 and 2016 we included 256 patients for whom MammaPrint and BluePrint were performed on pre-treatment core needle biopsies. The primary objective of the NBREaST II trial was to measure chemosensitivity or endocrine sensitivity in the molecular subgroups. Distant metastasis-free survival (DMFS), relapse-free survival (RFS) and breast cancer-specific survival (BCSS) were the endpoints for long-term follow-up. ResultsMammaPrint and BluePrint molecular sub-typing reclassified 9% (24/256) of tumours, reassigning more responsive patients to the HER2-Type and Basal-Type, and less responsive patients to the Luminal-Type category. Patients with Luminal A-Type tumours (n = 67, 26% of the total cohort) had a poor response when treated with neoadjuvant chemotherapy (NCT), but had the highest 5-year DMFS outcome (91.4%; 95% CI 78.6–96.7) of all molecular subgroups. Out of the IHC/FISH defined HER2+ tumours (n = 41), 37% were not classified as HER2-Type by BluePrint. Notably, in BluePrint HER2-Type tumours, we observed a higher pCR rate, whereas the 5-year DMFS was lower compared to IHC/FISH-defined HER2+ tumours. The pCR rate and 5-year outcome for patients with Basal-Type tumours were similar to IHC/FISH-defined TN tumours. ConclusionThese findings suggest that MammaPrint and BluePrint can predict chemosensitivity and 5-year outcomes more accurately compared to traditional pathological sub-typing, supporting informed decision-making.

POSB51 A Cost-Effectivess Analysis of Trastuzumab Emtansine Versus Trastuzumab for the Adjuvant Treatment of Patients with Residual Invasive HER2-Positive Breast Cancer in Portugal

To assess the cost-effectiveness of trastuzumab emtansine (T-DM1) versus trastuzumab for the adjuvant treatment of patients with residual invasive HER2-positive breast cancer (BC) after completion of preoperative systemic treatment in the Portuguese setting.

Perioperative Systemic Chemotherapy for Colorectal Liver Metastasis: Recent Updates.

Simple SummaryThe development of cytotoxic chemotherapy, targeted agents and immune check point inhibitors has improved survival outcomes and quality of life in patients diagnosed with metastatic colorectal cancer (CRC). Long-term survival and cure are possible in well-selected CRC patients with liver metastases (LM). The criteria for resectable LM and the eligibility of patients should be evaluated at the time of diagnosis or during the clinical course via a multidisciplinary team approach. The advantages of adjuvant chemotherapy after curative resection of LM are uncertain currently. Systemic preoperative chemotherapy may convert unresectable LM to a resectable type. However, the optimal combination of systemic drugs and treatment strategy has yet to be established. This article summarizes recent reports of perioperative systemic treatment for patients with colorectal liver metastases (CLM). This review provides an update for physicians involved in managing patients with CLM.The liver is the most common site of metastases for colorectal cancer. Complete resection in some patients with resectable liver metastases (LM) can lead to long-term survival and cure. Adjuvant systemic chemotherapy after complete resection of LM improves recurrence-free survival; however, the overall survival benefit is not clear. In selected patients, preoperative systemic treatment for metastatic colorectal cancer can convert unresectable to resectable cancer. This review will focus on patient selection, and integration of perioperative and postoperative systemic treatment to surgery in resectable and initially unresectable LM. Additionally, new drugs and biomarkers will be discussed.

Preoperative Systemic Therapy Versus Upfront Surgery in HER2-Positive Breast Cancer in the Real World.

PurposeTo compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world.MethodsAccording to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model.ResultsIncluded in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371–0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763–1.172, P, 0.609). For overall survival, there was no significant difference between the two groups.ConclusionThe HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04249440.

Abstract PS13-52: Preoperative systemic therapy versus upfront surgery in HER2-positive early breast cancer: A prospective nested case-control study in the real world

Abstract Purpose: To comparing the survival in different strategies, preoperative systemic treatment (PST) versus upfront surgery (US) in patients of HER2-positive early breast cancer in real-world.Methods: Eligible patients from 2012 to 2015 were classified as PST or US group prospectively, according to the real upfront treatment. The primary endpoint is disease-free survival (DFS), the second endpoint is overall survival (OS). All the outcomes were examined in unadjusted model, propensity score matching (PSM) model, and inverse probability of treatment weighting (IPTW) model. Results: Finally, 1067 eligible patients (215 in PST group, 852 in US group) were included into analysis (Table 1). In unweighted analysis, the cumulative DFS of PST group was significantly lower than US group (78.1% vs 87.7%, P&amp;lt;0.001), especially for those did not reach pathological complete response after PST. After adjusting the parameters, in PSM model (matching at 1:1 ratio), the DFS of PST group was significantly higher than the DFS of US group (HR, 0.57s2, 95%CI, 0.371~0.881, P, 0.012). In IPTW model, there was no significant difference of DFS between two groups (HR, 0.946, 95%CI, 0.763~1.172, P, 0.609). For OS, there were no significant difference between two groups in all three models. Conclusions: The patients in PST group have worse DFS than those in US group, mainly because of the unbalancing stage and biological risk. By real-world statistic method, after adjusting and making parameters comparable, the DFS of PST group is non-inferiority to the DFS of US group in IPTW model and even superior to US group in PSM model. *Proportions and medians are weighted using IPTW, all covariates included in the propensity analysis. Abbreviations: PSM, propensity score matching, IPTW, inverse probability of treatment weighting, PST, preoperative systemic treatment, US, upfront surgery, SMD, standardized mean difference, ER, estrogen receptor, PR, progesterone receptor.In IPTW model, the DFS rate of the PST group was 81.3% versus 80.8% of the US group, and the OS rate of the PST group was 92.1% versus 90.3% (Figure 2E, 2F), both having no significantly differences (Table 4). In further stratified analysis (Figure 3E, 3F), as in PSM model, the DFS and OS rate of the patients without pCR after PST (73.1%, 88.4%) were worse than those with pCR (96.6%, 99.3%) and US group (80.8%, 90.3%), respectively. Table 1. The clinicopathologic characteristics of two groups in PSM and IPTW modelsCharacteristicsNumber of casesUnweighted primary samplePSM modelIPTW model*PST group (215)US group (852)SMDPST group (145)US group (145)SMDPST group (765)US group (1021)SMDN (%)N (%)N (%)N (%)N (%)N (%)Age (years, medium, 95%CI)50, 39~6150, 33~640.0550, 40~6549, 34~620.1049, 39~6750, 31~640.03Stage T14588 (3.7)450 (52.8)0.7018(3.7)10 (6.9)0.03280 (10.5)450 (44.1)0.4672529157 (73.0)372 (43.7)118 (81.4)116 (80.0)635 (83.0)458 (44.9)38050 (23.3)30 (3.5)19 (13.1)19 (13.1)50 (6.5)113 (11.1)Stage N057137 (17.2)534 (62.7)1.04837 (17.2)32 (22.1)0.081310 (40.5)538 (52.7)0.2461596178 (82.8)318 (37.3)108 (81.4)113 (77.9)455 (59.5)483 (47.3)Grade1 and 252292 (42.8)430 (50.5)0.15477 (53.1)89 (61.4)0.168345 (45.1)493 (48.3)0.0643545123 (57.2)422 (49.5)68 (46.9)56 (38.6)420 (54.9)528 (51.7)ERNegative536142 (66.0)394 (46.2)0.40787 (60.0)68 (46.9)0.265386 (50.5)513 (50.2)0.004Positive53173 (34.0)458 (53.8)58 (40.0)77 (53.1)379 (49.5)508 (49.8)PRNegative649171 (79.5)478 (56.1)0.418108 (74.5)113 (77.9)0.081499 (65.2)625 (61.2)0.083Positive41844 (20.5)374 (43.9)37 (25.5)32 (22.1)266 (34.8)396 (38.8) Citation Format: Yang Hongjian, Xingfei Yu, Chen Wang, Zheng Yabing, Hu Jiejie, Xiying Shao, Liming Sheng, Juan Lin, Yuqin Ding, Haojun Xuan, Lijie Gong, Weiliang Feng, Chengdong Qin, Daobao Chen, Yang Yu. Preoperative systemic therapy versus upfront surgery in HER2-positive early breast cancer: A prospective nested case-control study in the real world [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-52.

Abstract PS8-36: Why is neoadjuvant treatment for patients with triple negative breast cancer of T1cN0 required ?

Abstract Background) Patients with early stage triple negative breast cancer(TNBC) are typically treated with surgery and chemotherapy, and sometimes radiotherapy. Despite effective neoadjuvant and adjuvant chemotherapies, the relapse rate is high and up to 50% of patients will experience disease recurrence including 10% of patients with stage I disease, and pCR is useful surrogate marker for patients with neoadjuvant treatment. Currently Neoadjuvant treatment is recommended for patients with TNBC of 2cm or larger at diagnosis. However, patients with T1 disease at diagnosis are mostly recommended with upfront surgery because uncertain clinical meaning of pCR and potential escalation of treatment for patients with non-pCR in this group. The aim of this study is to see whether patients with T1c of TNBC has different prognosis from T1a /b of same or different subtype and the potential benefit of neoadjuvant treatment exist or not. Material and methods) From 2000 to 2015, female patients treated with upfront surgery for stage I-III breast cancer were included. Patients of estrogen receptor positive disease and TNBC were further stratified according to the tumor size. The primary objective of this study was to see the different incidence of disease recurrence, for which chi-square test or Fisher’s exact tests were used. The secondary objective was recurrence free survival and distant disease free survival, for which Kaplan-Meier(K-M) graphs were generated and compared with log-rank test. Results) None of the TNBC patients experienced disease recurrence when they have T1a/b disease. However, patients with T1c disease showed similar incidence of disease recurrence with patients with T2 or T3 stage (89% vs. 86%), suggesting conventional T staging might not reflect real characteristics of TNBC. On the other hands, patients with ER positive disease less affected by tumor size, showing incidence of recurrent disease of T1a/b, T1c and T2 or over as 96.7%, 93.1% and 91.5% respectively. K-M graphs were generated and log-rank test showed worse survival of patients with T1c of TNBC than T1a/b and rather similar prognosis with patients with T2 or over. Conclusion) Effective adjuvant treatment, such as capecitabine had been proposed for patients with non-pCR. However, mixed results are reported, suggesting appropriate selection of patients is critical. While we need to define TNBC better, patients also need appropriate biomarker to decide whether they need escalated treatment after completion of neoadjuvant treatment. Given the dismal prognosis of T1c of TNBC, we propose this group of patients might benefit from preoperative systemic treatment with using pathologic result as surrogate marker. Citation Format: Hyang Suk Choi, In-Jeong Cho, Hany Noh, Kwang-Min Kim, Kyoung Tae Nam, Airi Han. Why is neoadjuvant treatment for patients with triple negative breast cancer of T1cN0 required ? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-36.

Breast cancer in women aged 75 years and older – tumour characteristics and treatment options

IntroductionAn optimal approach to older women with breast cancer is still a major challenge. In this paper, we present a retrospective analysis of treatment in patients aged 75 years and older who were treated at the Holycross Cancer Centre in 2015–2019.Material and methodsThe analysed group consisted of 259 women. For estimation of the general status of patients, we used the Geriatric 8 questionnaire. For every patient, an individual treatment plan was established. Survival analysis was performed; disease-free survival (DFS), cancer-specific survival, and overall survival (OS) were calculated by the Kaplan-Meier method. For DFS and OS, the Cox proportional-hazard regression was applied.ResultsThe mean age in the analysed group was 80 years. Stage I and II cancer accounted for over 80% of patients. Radical mastectomy was performed in 56% and breast-conserving surgery in over 34% of patients. Sentinel lymph node biopsy was used in 114 patients. Preoperative systemic treatment was applied in 34 and postoperative chemotherapy in 51 patients, respectively. Trastuzumab was used in 23 patients. Postoperative hormonal therapy was applied in 205 and radiotherapy in 178 patients. During the observation after the treatment 32 patients died, while 227 survived. In multivariate analysis for DFS hormonotherapy was statistically significant for OS clinical stage and hormonotherapy.ConclusionsThe treatment plan for older women consisted of surgery and radiation therapy, and systemic treatment should be always considered. The decision should be made by the breast cancer team.

Breast-conserving surgeries in HER-positive breast cancer patients are performed too rarely in Poland

Breast cancer is the most common cancer among women in Poland and worldwide; after lung cancer it is the second highest cause of death among females with malignancies. HER2 positive breast cancer occurs in ca.15–20% of all cases. More often than other subtypes, it affects younger patients and more often spreads metastasises to internal organs. The new drugs against the HER2 receptor significantly improve patients’ prognoses, regardless of the initial stage. The authors of the study involved 1503 patients with HER2 positive breast cancer from all stages (I–IV); 482 patients received preoperative systemic therapy (chemotherapy or hormonal therapy), 385 trastuzumab. Among the 1219 females qualified to surgery, 734 (60%) underwent a mastectomy, 485 (40%) had breast conserving therapy with adjuvant radiotherapy, some of them had preoperative systemic treatment.

PCN103 Cost-Effectiveness Analysis of Trastuzumab Emtansine for Adjuvant Treatment of Adult Patients with HER2+ EARLY Breast Cancer in Turkey

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related deaths in women. HER2+ breast cancer is an aggressive disease, which affects women in the earlier stages of life and results in substantial burden on patients, healthcare systems and society. Trastuzumab emtansine targets HER2+ tumor cells, delivering cytotoxic DM1 to HER2-expressing cells. The aim of this study is to demonstrate the cost effectiveness (CE) of trastuzumab emtansine compared with trastuzumab for the adjuvant treatment of residual invasive HER2+ eBC from the perspective of the Social Security Institution (payer) in Turkey. In the CE model, a six health state Markov model developed to compare trastuzumab emtansine with trastuzumab. The probabilistic Markov model is constructed using monthly cycle to explore the health outcomes and costs associated with the adjuvant treatment of patients with residual invasive HER2+ eBC after completion of preoperative systemic treatment. All utility values are age and gender adjusted to ensure that QALY estimate is line with the general population. Time horizon is 50 years. All costs including drug, supportive care, administration and adverse events based on public paid (SUT) prices. Discount rate of 3.5% applied for utilities & costs. The main model outcome is determined according to the incremental cost-effectiveness ratio (ICER) based on the quality-adjusted life years (Life Years LY). The analysis shows that the incremental benefit offered by trastuzumab emtansine is 1.606 QALYs (LY: 1.981) with an incremental cost of 11,183TRY (LY: 9,068TRY) when compared to trastuzumab. For eBC treatment and compared with trastuzumab, trastuzumab emtansine is a very cost-effective option when ICER is evaluated. Sensitivity analysis suggest that model is most sensitive to the treatment duration. Probabilistic sensitivity analyses show that results are stable.