Cycles Of Neoadjuvant Chemotherapy Research Articles

Pathologic Response Rates in Patients with Gastric Cancer Following FLOT Neoadjuvant Chemotherapy

Background: Gastric adenocarcinoma is among the most prevalent cancers associated with a high mortality rate. The multidrug neoadjuvant chemotherapy administered before and after surgery has attracted attention as a beneficial standard of care for managing this malignancy. Objectives: This study assessed the pathologic response of patients with gastric cancer who were treated with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). Methods: Patients with pathologically confirmed gastric adenocarcinoma without distant metastases were enrolled in this retrospective cohort study conducted at Imam Reza and Ghaem hospitals in Mashhad. Data regarding demographics, tumor status, treatment toxicity, and pathology results were collected using a predesigned questionnaire after four cycles of FLOT neoadjuvant chemotherapy. SPSS-26.0 was utilized to analyze the data, and a significance level of P < 0.05 was applied. Results: We evaluated data from 53 cases with a mean age of 51.1 ± 9.7 years. Diffuse adenocarcinoma was the most common finding in histology (54.7%). Pathologic complete response was observed in 16 (30.2%) patients. Most (69.8%) patients received only 7 out of 8 planned cycles. Concerning surgical margin, 46 (86.8%) patients achieved R0 tumor resection. Pathologic complete response was not significantly linked with age (P = 0.91), sex (P = 0.65), performance status (P = 0.2), tumor histology (P = 0.14), tumor grading (P = 0.07), tumor location (P = 0.8), and the number of neoadjuvant chemotherapy cycles (P = 0.9). Conclusions: Our findings demonstrated the relative clinical efficacy of neoadjuvant chemotherapy with the FLOT regimen administered before and after surgery. However, due to chemotherapy-related side effects, patients may not adhere to all eight prescribed cycles of chemotherapy.

Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination–deficient stage III/IV ovarian cancer: study protocol for cohort C of the open-label, phase 2, randomized controlled multicenter OPAL trial

BackgroundMaintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, has been shown to extend progression-free survival in patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. However, there are limited data on niraparib’s efficacy and safety in the neoadjuvant setting. The objective of Cohort C of the OPAL trial (OPAL-C) is to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment compared with neoadjuvant platinum-taxane doublet chemotherapy in patients with newly diagnosed stage III/IV ovarian cancer with confirmed homologous recombination–deficient tumors.MethodsOPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator’s discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator’s discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination–deficient. The primary endpoint is the pre–interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1.DiscussionOPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination–deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery.Trial registrationClinicalTrials.gov NCT03574779. Registered on February 28, 2022.

Abstract PO3-22-07: Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment

Abstract Background: Neoadjuvant chemotherapy (NACT) is increasingly used for axillary downstaging in clinically node-positive breast cancer patients, and a considerable proportion achieves axillary pathological complete response (ax-pCR). After NACT, axillary staging can be done by targeted axillary dissection (TAD). In case of metastases at TAD, axillary lymph node dissection (ALND) is offered regardless of metastases size. This contrasts primary surgery, where small sentinel node metastases (ypN0(i) and ypN1mi) and ≤2 positive sentinel nodes do not confer ALND, although a proportion of patients with small metastases have additional metastatic lymph nodes (LNs) in the axilla. So far, the residual metastatic burden in the axilla when TAD LNs are positive after NACT is unknown. If subgroups of patients with low residual metastatic burden in the axilla (non-TAD LNs) could be identified, these subgroups may be offered de-escalated axillary treatment. Therefore, we investigated the risk of residual metastatic burden in the axilla when the TAD LNs harbored metastases. Methods: We retrospectively retrieved DBCG data on patients staged by TAD after NACT in Denmark between 1.1.2016-31.8.2021. We registered: age, breast biopsy date, type of surgery, type of axillary surgery, count of LNs, sentinel nodes, and marked lymph nodes with and without metastases, including metastasis size, breast tumor histology and receptor subtype, breast tumor size at diagnosis and in the surgical specimen, malignancy grade and type of neoadjuvant treatment. We excluded patients with inflammatory breast cancer, < 4/>8 cycles of NACT, or a non-standard NACT regimen. The primary outcome was risk factors for having high ( >3), low (1-3), or no residual metastatic burden in the axilla when the TAD LNs harbored metastases. We modeled risk factors for both high and low residual metastatic burden in the axilla using multivariable logistic regression and constructed risk models based on the regression coefficients. Results: We identified 1626 patients receiving NACT and TAD in the inclusion period. After excluding ineligible patients and patients who achieved ax-pCR with no subsequent ALND (46%), the study included 383 patients with positive LNs at TAD for further analysis: thereof 188, 127, and 68 with 0, 1-3 and >3 positive non-TAD LNs, respectively. In the adjusted logistic regression analysis, we found that breast pCR (OR= 0.06, 95% CI < .01-0.41, p < .001) and a low proportion of positive TAD LNs (0-66% vs >66%) (OR=0.32, 95% CI 0.17-0.58, p = < .001) were associated with low risk of high residual metastatic burden in the axilla. Patients with one or both low-risk factors present had an 8% (14 of 176 patients) risk of high residual metastatic burden in the axilla. The predictive value of the model for having < 3 non-TAD LN metastases was 92%. When analyzing the 315 patients with ≤3 positive non-TAD LNs, the adjusted logistic regression analysis of 1-3 vs 0 positive non-TAD LNs showed that ypN0(i) in the TAD LN (OR=0.14, 95% CI 0.04-0.53, p = 0.002), small tumor size at diagnosis (20-49 mm vs ≥ 50 mm) (OR = 0.29, 95% CI 0.14-0.60, p = 0.002), breast pCR (OR= 0.38, 95% CI 0.15-0.98, p = 0.04) and low proportion of positive TAD LNs (33-66% vs >66%) (OR= 0.46, 95% CI 0.27-0.77, p = 0.01) were associated with no residual metastases in the axilla. Using these risk factors, 19% (11/58) of the patients in the lowest risk quartile had further metastatic spread to the axilla. Conclusion: Based on an extensive breast cancer registry, we find that breast pCR, low proportion of positive TAD LNs, small metastases, and small tumor size are associated with low risk of residual metastatic LNs in the axilla when the TAD LNs are positive after NACT. With these risk factors, we propose two models to identify patients with low non-TAD residual metastatic burden and patients with a high likelihood of no further metastases. The models can guide breast surgeons in de-escalating axillary treatment in these groups. Citation Format: Frederikke Munck, Maj-Britt Jensen, Ilse Vejborg, Maria Gerlach, Maja Maraldo, Niels Kroman, Tove Tvedskov. Predicting Additional Axillary Metastases in Breast Cancer Patients with Positive Targeted Axillary Dissection Lymph Nodes after Neoadjuvant Treatment [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 PO3-22-07.

Abstract PO3-03-12: Factors associated with response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer

Abstract Background: The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) became a standard-of-care for the treatment of early-stage triple negative breast cancer (TNBC) after the phase III KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates and event free survival with the combination. To date, clinical predictors of response to pembro with NAC are lacking. We sought to identify real-world clinical characteristics and treatment variables associated with response to NAC with pembro. Methods: We performed a single institution, retrospective study of early-stage TNBC patients diagnosed between February 1st, 2020 and December 1st, 2022 who were treated with NAC and pembro. Patients who had not undergone definitive surgery were excluded. Demographic information, clinical and pathologic characteristics, and treatment data were collected. pCR was defined as ypT0/Tis and ypN0. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. This study was approved by an Institutional Review Board. Results: Of the 94 patients analyzed, 93 were female and 1 was male. The median age was 55 years (IQR 47 – 61.8) and median body mass index (BMI) was 30 (24.1-33.6). Self-reported racial/ethnic groups included 37 non-Hispanic White (39.4%), 33 Hispanic (35.1%), 13 Asian (13.8%), 7 Black (7.4%), and 4 other/unknown (4.3%). 8 (8.5%) and 2 (2.1%) of patients had deleterious germline BRCA1+ and BRCA2+ mutations, respectively. The majority of patients had invasive ductal histology (90.4%), clinical T2 stage (68.1%), and node negative (55.3%) disease. 61 (64.9%) patients completed the planned 8 cycles of NAC, while 42 (44.7%) completed the planned 8 cycles of neoadjuvant pembro. A pCR (ypT0/Tis ypN0) was achieved in 60 (63.8%) of the 94 patients. Among those who achieved a pCR, 32 (53.3%) completed the prescribed course of NAC and pembro in combination, whereas 9 (47.1%) of the 34 patients with residual disease did not. In univariate analyses, patients under 55 years at time of diagnosis (vs. age >55 years), higher ki-67, those completing the prescribed course of NAC, those completing the prescribed course of pembro, the months from start of NAC to surgery, and the months from start of pembro to surgery were associated with pCR. The duration from start of NAC or pembro to surgery overlapped considerably with the response explained by completion of NAC or pembro, respectively. Although pCR estimates were lower for Hispanic (60.6%) and non-Hispanic White patients (Black: 57.1%, Asian: 53.8%, and Other: 50%) when compared to non-Hispanic White patients (73.0%), the results were not statistically significant. In multivariate analyses, patients under 55 years at time of diagnosis (OR 3.06, 95% CI:1.18-8.0, p=0.02) and those completing the full course of pembro (OR 2.86, 95%CI: 1.08-7.58, p=0.034) had improved rates of pCR. BMI, race, BRCA1/2 status, histology, clinical T and N stage, grade, time between start/end of NAC and IO to surgery were not significantly associated with pCR on multivariate analysis. Conclusion: In our experience, younger TNBC patients were more likely to achieve a pCR with NAC with pembro. Moreover, the completion of the planned course of pembro prior to surgery was also associated with improved pCR rates. These findings suggest that adherence to neoadjuvant pembro prior to surgery may be more important than the completion of the NAC. Further research to identify the optimal exposure of NAC with pembro is needed to refine treatment recommendations in this high-risk population. Citation Format: Alexis LeVee, Megan Wong, Sarah Flores, Nora Ruel, Heather McArthur, James Waisman, Joanne Mortimer. Factors associated with response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer [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 PO3-03-12.

Abstract RF02-07: Precocious modulation of metabolic and immunological parameters predicts tumor response to fasting-mimicking diet plus chemotherapy in patients with early stage TNBC

Abstract Background: Preclinical studies showed that severely calorie restricted fasting-mimicking diets (FMDs) enhance the antitumor efficacy of chemotherapy (CT) or immunotherapy (IO) in murine triple negative breast cancer (TNBC) models. These effects are mediated by a combination of blood glucose reduction and positive immunomodulatory effects. Moreover, combining fasting and metformin produced synergistic anticancer effects in a broad range of tumor models. The BREAKFAST trial was designed to investigate if FMD, plus/minus metformin, could increase the antitumor activity of neoadjuvant CT in patients with stage I-III TNBC. Methods: BREAKFAST (NCT04248998) is a randomized, non-comparative, phase II, pilot trial that enrolled stage I-III (cT>1 cm) TNBC patients (pts) candidate to receive 4 cycles of neoadjuvant CT with doxorubicin-cyclophosphamide every 3 weeks, followed by 12 cycles of weekly paclitaxel. Pts were randomized 1:1 to receive: CT plus 5-day FMD every 3 weeks, up to 8 cycles (arm A); CT plus FMD plus daily metformin (1700 mg) (arm B). The primary study endpoint was the rate of pCR in either experimental arm. Secondary/exploratory endpoints included safety, compliance, and biomarker analyses based on blood metabolomics and tumor transcriptomics analyses at different timepoints. Results: Between June 2020 and February 2022 we enrolled 30 pts. Then, the study was interrupted after the introduction of chemo-immunotherapy (CT-IO) as a standard neoadjuvant therapy for early stage TNBC pts. Among 30 pts, 13 were treated with CT plus FMD, while 17 pts received CT plus FMD plus metformin. Overall, pCR rate was 56.6%, i.e., significantly higher than pCR rates reported with anthracycline-taxane CT alone in previous phase II/III trials (26-39%), with no significant differences among treatment arms (p=0.49). The FMD acutely reduced blood glucose, insulin and LDH levels, which reflects a reduction in systemic and/or tumor glucose metabolism. Of note, precocious LDH reduction was more pronounced in patients undergoing pCR. RNA-seq analysis of tumor samples revealed a significant downmodulation of glycolysis and TCA cycle pathways after one treatment cycle, paralleled by an increase of intratumor activated T cells, memory T cells and NK cells, as estimated by deconvolution analyses of tumor transcriptomic data. Of note, these changes were observed only in patients achieving pCR. While intratumor metabolic changes were similar in the two treatment arms, the modulation of intratumor immunity was more pronounced in patients not receiving metformin. Conclusion: Preoperative CT plus cyclic FMD (plus/minus metformin) results in excellent pCR rates in localized TNBC patients. Early on-treatment downregulation of systemic and intratumor metabolic parameters related to glucose metabolism predicts pCR, and this is independent of metformin use. Based on results of this study, we recently initiated a large, multicentric trial, namely the BREAKFAST-2 (NCT05763992) study, which will investigate if adding cyclic FMD to neoadjuvant CT-IO increases pCR rates in ~ 145 pts with stage II-III TNBC. Citation Format: Francesca Ligorio, Giovanni Fucà, Andrea Vingiani, Fabio Iannelli, Riccardo Lobefaro, Leonardo Provenzano, Lucrezia Zanenga, Cristina Ferraris, Antonino Belfiore, Silvia Brich, Alessia Bertolotti, Gianfranco Scaperrotta, Catherine Depretto, Antonia Martinetti, Elisa Sottotetti, Paola Antonia Corsetto, Giulia Valeria Bianchi, Giuseppe Capri, Secondo Folli, Saverio Minucci, Marco Foiani, Massimiliano Pagani, Giancarlo Pruneri, Filippo De Braud, Claudio Vernieri. Precocious modulation of metabolic and immunological parameters predicts tumor response to fasting-mimicking diet plus chemotherapy in patients with early stage TNBC [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 RF02-07.

Abstract PO4-03-13: High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors suggesting potential anti-B7-H3 therapy in triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancer. B7 homolog 3 protein (B7-H3), also known as CD276, is an emerging immune checkpoint molecule, which plays a dual role in the immune system. Multiple anti-B7-H3 therapies has been raised, such as DS-7300, MGA271, MGD009, and B7-H3 chimeric antigen receptor T-cell immunotherapy (CAR-T). However, the expression of B7-H3 in TNBC and its value as a biomarker identifying therapeutic options has not been elucidated Methods: A total of 165 samples (83 non-TNBC and 82 TNBC) were included in this study, and 6 samples included paired para-tumor samples. In addition, 30 TNBC patients receiving standardized neoadjuvant chemotherapy (NAT) were recruited. After 8 cycles of NAT, the response to NAT was assessed by RECIST1.1 criterion before surgical operation. Moreover, multiple public cohorts of breast cancer and TNBC were obtained, including the TCGA dataset, the METABRIC dataset, the GSE176307 (durvalumab-based therapy) dataset, the PRJNA558949 (durvalumab-based therapy) dataset, the GSE194040 (paclitaxel-based therapy) dataset, and the GSE34138 (anthracycline-based therapy) dataset. Based on multiple in-house and public cohorts, we investigated the expression features of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in mouse model. We also developed a novel classifier combined B7-H3 and PD-L1 expression in TNBC. Results: B7-H3 was highly expressed in tumor tissues in the in-house and the TCGA cohorts. B7-H3 expression did not differ significantly between non-TNBC and TNBC samples in the in-house and the TCGA cohorts, excepting for the METABIRC cohort. There was no notable difference in CD8+ cells infiltration between B7-H3 low and high expressed non-TNBC samples, but CD8+ cells was notably higher in the B7-H3 low expressed TNBC samples. The similar findings were also observed in the TCGA and the METABIRC cohorts. In addition, enrichment analysis of transcriptome data and analysis of in-house samples showed that B7-H3 was positively related to most collagens. Moreover, anti-B7-H3 therapy significantly inhibited tumor growth in mouse TNBC model, notably increased immune cells infiltration, and also reduced collagen deposition within the tumor. Given the notable value of PD-L1 in predicting immunotherapy responses, we also combined B7-H3 and PD-L1 expression to establish a novel subtyping strategy. TNBC patients with B7-H3highPDL1low feature exhibited the lowest anti-tumor immune infiltration and higher collagen deposition level. In the durvalumab-dependent cohort, paclitaxel-dependent cohort, anthracycline-dependent cohort, and our recruited NAT cohort, the B7-H3highPDL1low subgroup exhibited the lowest therapeutic response. Conclusions: Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression that could potentially be applied to predict the therapeutic responses in TNBC, and suggests a potential biomarker-guided anti-B7-H3 therapy. Based on the classifier, we can select potential beneficiaries to deliver personalized medical services. Citation Format: Jie Mei, Yun Cai, Ziyi Fu, Yongmei Yin. High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors suggesting potential anti-B7-H3 therapy in triple-negative breast cancer [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 PO4-03-13.

Abstract PO5-17-03: Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia

Abstract Introduction: Breast cancer (BC) is the most frequent neoplasm in Colombia. In contrast to high-income countries, the expected 5-year overall survival (OS) remains below 80% over the last years. Neoadjuvant chemotherapy (NACT) has reduced the risk of relapse and death by achieving higher pathological complete response (ypCR) rates, but delays and dose reductions could impact prognosis negatively. We have previously reported the outcomes of NACT from a real-world multicenter historical cohort of Colombian early and locally advanced BC patients. We aimed to analyze NACTRelative Dose Intensity (RDI) and protraction data as related to clinical outcomes in the same cohort. Methods: We performed a secondary analysis of the primary database of 312 BC patients treated with NACT where ypCR rate was 34·6%, with 88·2% 5-year OS. We considered RDI and protraction as independent variables for the same outcomes. The RDI was estimated using the Hrynuik method, and protraction was defined as the difference between planned and actual completion time for the NACT exceeding 7 days from standard 21-day cycles. Chemotherapy regimens are based on the National Hematology and Oncology Association (ACHO) guidelines. We excluded cases with missing or conflicting data. Univariate, and bivariate analysis, and partition survival trees were performed to examine variable interactions. Results: From the original cohort of 312 patients, 47 and 7 additional patients were excluded due to missing protraction and RDI data, respectively; the final analysis included 261 and 254 patients, respectively. The average days to complete planned chemotherapy cycles were 154,4 (SD 32,29 days). 203 patients (77,8%), 26 patients (10%), and 11 patients (4,2%) received complete 8,7 and 6 NACT cycles, respectively. Overall, 175 patients (67%) had protracted chemotherapy cycles, being highest in the 7-cycle subgroup (77%). 169 patients (66,5%) had a dose intensity over 85% and 90 patients (35.43%) achieved an RDI of 100% or more. The mean RDI for the cohort was 79,8% (SD 19,91%) and it differed according to expression profile subgroups in decreasing order as follows: HER2 pure 98,85% (SD 19,59%), Luminal A 96,03% (SD 21,28%), Triple Negative 97,81% (SD 19,73%), Luminal B HER+ and HER2- being lowest with 90,43% (SD 19,47%) and 87,75% (SD 23,22%), respectively. Neither NACT RDI nor protraction was associated significantly with ypCR, conservative surgery, or all-cause OS. Although statistically not-significant, sensitivity analysis through different RDI thresholds (20%-100%) demonstrated improved discriminatory capacity over ypCR for RDI >= 85%. Conclusion: On average, NACT-RDI greater than 85% was observed in Colombian patients with early and locally advanced BC similar to other cohorts. However, it was not associated with ypCR, conservative surgery, or OS. Also, NACT protraction beyond 7 days did not adversely affect clinical outcomes. However, this conclusion is limited due to the retrospective nature and loss of real-world data. Adverse events and their impact on RDI were not analyzed either. Further research is warranted to understand RDI's impact on clinical outcomes, and a large-scale trial is proposed to validate these findings. Citation Format: Alejandro Murillo, Andres Acevedo, Santiago Betancur, Mariana Borras-Osorio, Isabel Munevar, William Mantilla, Luis Pino. Relative Dose Intensity and Protraction of Neoadjuvant Chemotherapy in Early-Stage and Locally Advanced Breast Cancer: A collaborative multicenter analysis in Colombia [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 PO5-17-03.

Abstract PO1-06-04: Immune checkpoint inhibitors for triple-negative inflammatory breast cancer (INCORPORATE): an international multicenter retrospective analysis

Abstract Background: Inflammatory breast cancer (IBC) is an aggressive clinical presentation of breast cancer (BC). Immune checkpoint inhibitors (ICIs) combined with chemotherapy provided an overall survival (OS) benefit in the metastatic setting and an even-free survival (EFS) benefit in patients (pts) with early triple-negative (TN) BC, respectively. Patients with TN-IBC were under-represented or excluded in pivotal trials and commonly not evaluated in subgroup analyses. Methods: We conducted a retrospective, multicenter, international, observational study to evaluate the clinical benefit of ICIs in pts with TN-IBC (defined as cT4d per AJCC TNM, 8th ed., ER < 1% and PgR < 1%, HER2: negative). Pts with early-stage TN-IBC were included if they received an ICI combined with neoadjuvant chemotherapy (NACT) (Group 1). Pts with metastatic TN-IBC were included if they received ICI monotherapy or in association with first-line chemotherapy (Group 2). Treatment was administered according to guideline recommendations (in PD-L1+ metastatic IBC and regardless of PD-L1 in early IBC), in clinical trials, or off-label (regardless of PD-L1 expression status in metastatic IBC). Endpoints were pathological complete response (pCR) and 1-year EFS rate for group 1 (calculated from date of first cycle of NACT to any recurrence or death), and progression-free survival (PFS) for group 2. Correlative analyses were provided (significance at p-value < 0.05). Results: We included 59 pts from 8 international referral centers. 15 pts had early IBC (Group 1), and 44 pts had metastatic disease (Group 2). Patient characteristics and outcomes are shown in Table 1. Among the 15 pts from Group 1, 10 received anthracycline, taxane and carboplatin-based (AC-CbT) NACT with pembrolizumab, 3 neoadjuvant paclitaxel-carboplatin chemotherapy with pembrolizumab, 2 neoadjuvant nab-paclitaxel with atezolizumab. One pt progressed on NACT, 2 pts are still receiving NACT. Among 13 pts evaluable for response, 6/13 (46%) achieved a pCR. After a median follow-up of 7.1 months, the median EFS was 12.9 months and the 1-year EFS rate was 70%. The median OS was 15.7 months. Among pts from Group 2, PD-L1 status was positive (IC 1% or CPS 10) in 27/44 pts (61%), negative in 5/44 pts (11%) and unknown in 6/44 pts (13%). At a median follow-up of 24.3 months, median PFS and OS were 4.1 and 15.7 months. As backbone chemotherapy in first line setting, 6 pts received AC-CbT regardless of PD-L1 status (mPFS: 8.6 months), 21 taxane-based/anthracycline-free chemotherapy (mPFS: 5.3 months), 14 other chemotherapy regimens (mPFS: 2.1 months) and 3 single-agent immunotherapy (mPFS: 50.1 months). Three of 6 patients who received AC-CbT underwent surgery and radiotherapy. In Group 2, after adjusting for the number of metastatic sites (>1 vs. 0-1), PD-L1 status (positive vs. negative vs. unknown) and de novo metastatic disease (yes vs. no), AC-CbT chemotherapy (HR 0.05; 95% CI: 0.01-0.56; p=.015) and taxane-based chemotherapy (HR 0.20; 95% CI: 0.06-0.68; p=.009) were both associated with longer PFS. Conclusions: This multicenter retrospective analysis of TN-IBC treated with combination of chemotherapy and IOs showed relatively low pathology response, EFS and clinical benefit suggesting need to further investigate the role of immunotherapy in this aggressive disease. Table 1. Patient characteristics and outcomes Citation Format: Carmine Valenza, Dario Trapani, Paola Zagami, Gabriele Antonarelli, Luca Boscolo Bielo, Eleonora Nicolò, Joana Mourato Ribeiro, Lorenzo Guidi, Carolina REDUZZI, Martina Spotti, Elisabetta Munzone, Javier Cortés, Barbara Pistilli, Sara Tolaney, Naoto Ueno, Rachel Layman, Massimo Cristofanilli, Lisa Carey, Filipa Lynce, Wendy Woodward, Giuseppe Curigliano. Immune checkpoint inhibitors for triple-negative inflammatory breast cancer (INCORPORATE): an international multicenter retrospective analysis [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 PO1-06-04.

Abstract PO1-09-11: Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer and has been utilized in multiple clinical trials assessing the efficacy of novel therapies. Pathologic complete response (pCR) following NAC is associated with improved survival outcomes in breast cancer and pCR is a commonly used endpoint in clinical trials. Despite improvements in breast cancer survival using modern treatment regimens, Black women continue to experience worse survival outcomes as compared to White women. The objective of this study was to evaluate the association between race and clinical outcomes, specifically pCR rate, recurrence free survival and overall survival, in patients undergoing neoadjuvant chemotherapy at our institution. Methods: We conducted a retrospective review of patients who completed at least 75% of the recommended cycles of neoadjuvant chemotherapy for breast cancer between 2010 and 2016 and underwent surgery. Receptor subtypes were defined as HR+/HER2-negative, HER2+ or triple-negative. The association between race and pCR, defined as ypT0/ypTis ypN0, and survival endpoints of overall survival and recurrence free survival were analyzed using multivariable logistic regression and Cox proportional hazard models. Results: A total of 532 women met the inclusion criteria, 323 (60.7%) were White, 188 (35.3%) were Black and 21 (3.9%) were other/unknown. Median follow-up was 65 months. The receptor subgroups consisted of 195 (36.7%) HR+/HER2-negative cancers, 193 (36.3%) HER2+ cancers and 144 (27.1%) triple-negative cancers. No significant association between race and receptor subtype (p=0.55) or pre-treatment clinical stage (p=0.96) was observed. The overall observed pCR rate was 19% for Black patients and 27% for White patients, demonstrating a significantly different pCR rate by race in multivariate analysis (odds ratio of pCR White vs Black of 1.75; p=0.02). The largest discrepancy in pCR rate between White and Black patients was within subjects with triple-negative disease (pCR rate 44% White patients vs 27% Black patients, p=0.03). There was no association between recurrence free survival and race in univariate analysis (p=0.15). A significant difference in overall survival by race was observed using multivariable Cox proportions hazard model (hazard ratio Black vs White 1.77; p=0.03). Conclusions: In this retrospective analysis of patients receiving neoadjuvant chemotherapy, Black patients experienced a significantly lower pCR rate compared to White patients, with the biggest gap identified within triple-negative breast cancers. During the study period, Black patients also experienced a lower overall survival rate compared to White patients. Differences in the ability to achieve a pCR may be a contributing factor to the worse survival outcomes of Black patients. Citation Format: Chad Livasy, Erin Donahue, Brittany Neelands, Lejla Hadzikadic-Gusic, Terry Sarantou, Mckenzie Needham, Alicia Patrick, Arielle Heeke, Antoinette Tan, Richard White. Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer [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 PO1-09-11.

Impact of neoadjuvant pembrolizumab adherence on pathologic complete response in triple-negative breast cancer: a real-world analysis.

The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) is standard of care for the treatment of early triple-negative breast cancer (TNBC) after KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates with the combination. However, the optimal treatment strategy for TNBC remains uncertain as questions persist about which patients benefit from pembro and the best treatment schedule and regimen. We identified real-world clinical characteristics and treatment variables associated with response to NAC plus pembro. Patients with early TNBC treated with NAC plus pembro between February 2020 and September 2023 were identified. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. Cox proportional hazard prediction models were used to identify predictors of invasive disease-free survival and overall survivalin this cohort. A pCR was achieved in 75 (63.6%) of 118 patients. Age at diagnosis (P = .04), Ki-67 (P = .004), duration from start of pembro to surgery (P = .006) and NAC to surgery (P = .01), number of cycles of pembro (P = .04) and NAC (P = .02), and completion of at least 8 cycles of pembro (P = .015) and NAC (P = .015) were each significantly associated with pCR in univariate analysis. In multivariate analysis, patients younger than 55 years at time of diagnosis (vs age > 55 years) and those completing at least 8 cycles of pembro remained predictive of pCR (OR's 2.50, 2.49, P = .035 and .037, respectively). In this real-world analysis of patients with TNBC treated with NAC plus pembro, younger age and the completion of at least 8 cycles of pembrolizumab were associated with pCR.

Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer.

There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT were administered in 167 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response (HR 3.11, 95% CI 1.73-5.58, P<0.001) based on cut-off value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels <37IU/L (median survival; 35.5 vs. 20.9mo, P<0.001) and CA19-9 levels ≥37IU/L (median survival; 34.3 vs. 17.8mo, P=0.03). In patients suspected to be Lewis antigen negative, predictive performance of MTV was found to be limited (P=0.84). Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.

Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.

Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.

ASO Visual Abstract: Expanding the Use of HIPEC in Ovarian Cancer at the Time of Interval Debulking Surgery to FIGO Stage IV After Six Cycles of Neoadjuvant Chemotherapy: A Prospective Analysis of Perioperative and Oncologic Outcomes.

ASO Visual Abstract: Expanding the Use of HIPEC in Ovarian Cancer at the Time of Interval Debulking Surgery to FIGO Stage IV After Six Cycles of Neoadjuvant Chemotherapy: A Prospective Analysis of Perioperative and Oncologic Outcomes.

Outcomes of neoadjuvant chemotherapy and radical hysterectomy for locally advanced cervical cancer at Kigali University Teaching Hospital, Rwanda: a retrospective descriptive study

BackgroundHalf of countries in Africa lack access to radiation (RT), which is essential for standard treatment of locally advanced cervical cancers. We evaluated outcomes for patients treated with neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in settings where no RT is available.MethodsWe performed a retrospective descriptive study of all patients with FIGO stage IB2-IIA2 and some exceptional stage IIB cases who received NACT and surgery at Kigali University Teaching Hospital in Rwanda. Patients were treated with NACT consisting of carboplatin and paclitaxel once every 3 weeks for 3–4 cycles before radical hysterectomy. We calculated recurrence rates and overall survival (OS) rate was determined by Kaplan-Meier estimates.ResultsBetween May 2016 and October 2018, 57 patients underwent NACT and 43 (75.4%) were candidates for radical hysterectomy after clinical response assessment. Among the 43 patients who received NACT and surgery, the median age was 56 years, 14% were HIV positive, and FIGO stage distribution was: IB2 (32.6%), IIA1 (7.0%), IIA2 (51.2%) and IIB (9.3%). Thirty-nine (96%) patients received 3 cycles and 4 (4%) received 4 cycles of NACT. Thirty-eight (88.4%) patients underwent radical hysterectomy as planned and 5 (11.6%) had surgery aborted due to grossly metastatic disease. Two patients were lost to follow up after surgery and excluded from survival analysis. For the remaining 41 patients with median follow-up time of 34.4 months, 32 (78%) were alive with no evidence of recurrence, and 8 (20%) were alive with recurrence. One patient died of an unrelated cancer. The 3-year OS rate for the 41 patients who underwent NACT and surgery was 80.8% with a recurrence rate of 20%.ConclusionsNeoadjuvant chemotherapy with radical hysterectomy is a feasible treatment option for locally advanced cervical cancer in settings with limited access to RT. With an increase in gynecologic oncologists skilled at radical surgery, this approach may be a more widely available alternative treatment option in countries without radiation facilities.

Perioperative Chemotherapy for Gastro-Esophageal or Gastric Cancer: Anthracyclin Triplets versus FLOT.

Background: The FLOT4-AIO trial (2019) showed improved survival with perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) compared to anthracyclin triplets in gastric cancer treatment. It is unclear whether these results extend to real-world scenarios in the Netherlands. This study aimed to compare outcomes of perioperative FLOT to anthracyclin triplets in a real-world Dutch gastric cancer population. Methods: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) gastric or gastro-esophageal junction carcinoma between 2015-2021 who received neoadjuvant FLOT or anthracyclin triplets were selected from the Netherlands Cancer Registry. The primary outcome was overall survival (OS), analyzed through multivariable Cox regression. Secondary outcomes included pathological complete response (pCR), neoadjuvant chemotherapy cycle completion, surgical resection rates, and adjuvant therapy. Results: Adjusted OS showed no significant survival benefit (HR = 0.88, 95% CI 0.77-1.01, p = 0.07), even though the median OS was numerically improved by 8 months with FLOT compared to anthracyclin triplets (48.1 vs. 39.9 months, p = 0.16). FLOT patients were more likely to undergo diagnostic staging laparoscopies (74.2% vs. 44.1%, p < 0.001), had higher rates of completing neoadjuvant chemotherapy (OR = 1.35, 95% CI 1.09-1.68, p = 0.007), receiving adjuvant therapy (OR = 1.34, 95% CI 1.08-1.66, p = 0.08), and achieving pCR (OR = 1.52, 95% CI 1.05-2.20, p = 0.03). No significant differences were observed in (radical) resection rates. Conclusion(s): Real-world data showed no significant OS improvement for FLOT-treated patients compared to anthracyclin triplets, despite more staging laparoscopies. However, FLOT patients demonstrated higher rates of neoadjuvant therapy completion, proceeding to adjuvant therapy, and increased pCR rates. Therefore, we recommend the continued use of neoadjuvant FLOT therapy in the current clinical setting.

A case of pathological complete regression in combined modality treatment of resectable Her2/neu-positive gastric cancer

Background. Overexpression of Her2neu occurs in 15–20% of patients with gastric cancer and correlates with an unfavorable prognosis. Case report. We report a case of pathological complete regression of resectable gastric cancer with Her2/neu overexpression. The patient received combined modality treatment including 8 cycles of neoadjuvant chemotherapy with mFLOT + trastuzumab followed by R0 resection. The addition of targeted therapy did not have a negative impact on the perioperative period. Histolohical examination of the surgical specimen revealed pathological complete response (Mandart TGR1). Currently, the patient has been followed-up for 27 months without signs of disease relapse. Conclusion. Total neoadjuvant chemotherapy with mFLОТ+ trastuzumab for operable gastric cancer with Her2/neu overexpression allows us to hope for improved long-term treatment outcomes.

The combination of preoperative celiac axis stenting and neoadjuvant chemotherapy in an elderly patient with pancreatic cancer: a case report

BackgroundCeliac axis stenosis (CAS) is frequently observed in patients undergoing pancreaticoduodenectomy (PD). This poses challenges because of the potential disruption of the hepatic arterial blood flow.Case presentationWe present the case of an 81-year-old woman diagnosed with pancreatic head cancer and severe CAS caused by calcification. The patient received neoadjuvant chemotherapy (NAC) and underwent preoperative endovascular stenting of the celiac axis to restore blood flow. After two cycles of NAC, subtotal stomach-preserving PD was performed. An intraoperative assessment of the hepatic arterial blood flow determined that it was well maintained. PD was performed using the standard technique; specialized techniques were not necessary. Importantly, no ischemic complications were encountered.ConclusionThis case report describes the successful combination of preoperative celiac axis stenting, NAC, and surgical intervention for the management of CAS in an elderly patient with pancreatic cancer. This approach offers a potential solution for maintaining the hepatic arterial blood flow in the presence of CAS without vascular reconstruction, particularly in elderly individuals.

Prospective validation of the role of PET/CT in detecting disease after neoadjuvant chemotherapy in advanced ovarian cancer.

The study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC). This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III-IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar's test. In the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05). 2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC. 2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery. • Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy. • 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT. • Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.

Operative treatment of pulmonary primitive neuroectodermal tumor: a case report and literature review

BackgroundPulmonary primitive neuroectodermal tumor (PNET), a member of the Ewing sarcoma family of tumors, is a rare malignancy that is associated with a grim prognosis. To date, fewer than 30 cases of pulmonary PNET have been reported. In this case report, we present the clinical details of a 12-year-old girl with pulmonary PNET who underwent surgical treatment. We also conducted an analysis and summary of other relevant studies and the surgical outcomes.Case presentationIn May 2018, a 12-year-old girl was admitted with symptoms of cough and blood-tinged phlegm. A computed tomography scan revealed a large mass, measuring 12.9 cm × 8.1 cm, in the right middle and lower lungs. A percutaneous lung biopsy confirmed poorly differentiated tumor cells with a nested growth pattern. Immunohistochemical staining demonstrated positive expression of CD99, CD56, Vimentin, and Synaptophysin. The patient was diagnosed with pulmonary PNET. Following three cycles of neoadjuvant chemotherapy, a substantial reduction in tumor volume was observed. Subsequently, the patient underwent a surgical procedure involving pneumonectomy and partial resection of the left atrium with the assistance of cardiopulmonary bypass. The patient was discharged 37 days after surgery. During a three-year follow-up period, she exhibited no signs of tumor recurrence and has successfully returned to school.ConclusionsThis case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.

An ultrasound-based nomogram model in the assessment of pathological complete response of neoadjuvant chemotherapy in breast cancer.

We aim to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) in breast cancer patients by constructing a Nomogram based on radiomics models, clinicopathological features, and ultrasound features. Ultrasound images of 464 breast cancer patients undergoing NAC were retrospectively analyzed. The patients were further divided into the training cohort and the validation cohort. The radiomics signatures (RS) before NAC treatment (RS1), after 2 cycles of NAC (RS2), and the different signatures between RS2 and RS1 (Delta-RS/RS1) were obtained. LASSO regression and random forest analysis were used for feature screening and model development, respectively. The independent predictors of pCR were screened from clinicopathological features, ultrasound features, and radiomics models by using univariate and multivariate analysis. The Nomogram model was constructed based on the optimal radiomics model and clinicopathological and ultrasound features. The predictive performance was evaluated with the receiver operating characteristic (ROC) curve. We found that RS2 had better predictive performance for pCR. In the validation cohort, the area under the ROC curve was 0.817 (95%CI: 0.734-0.900), which was higher than RS1 and Delta-RS/RS1. The Nomogram based on clinicopathological features, ultrasound features, and RS2 could accurately predict the pCR value, and had the area under the ROC curve of 0.897 (95%CI: 0.866-0.929) in the validation cohort. The decision curve analysis showed that the Nomogram model had certain clinical practical value. The Nomogram based on radiomics signatures after two cycles of NAC, and clinicopathological and ultrasound features have good performance in predicting the NAC efficacy of breast cancer.