Neoadjuvant Treatment In Patients Research Articles

Histological prognosticators in neoadjuvant naive oesophageal cancer patients.

Prognosis of oesophageal cancer is primarily based upon the TNM stage of the disease. However, even in those with similar TNM staging, survival can be varied. Additional histopathological factors including venous invasion (VI), lymphatic invasion (LI) and perineural invasion (PNI) have been identified as prognostic markers yet are not part of TNM classification. The aim of this study is to determine the prognostic importance of these factors and overall survival in patients with oesophageal or junctional cancer who underwent transthoracic oesophagectomy as the unimodality treatment. Data from patients who underwent transthoracic oesophagectomy for adenocarcinoma without neoadjuvant treatment were reviewed. Patients were treated with radical resection, with a curative intent using a transthoracic Ivor Lewis or three staged McKeown approach. A total of 172 patients were included. Survival was poorer when VI, LI and PNI were present (p<0.001), with the estimated survival being significantly worse (p<0.001) when patients were stratified according to the number of factors present. Univariable analysis of factors revealed VI, LI and PNI were all associated with survival. Presence of LI was independently predictive of incorrect staging/upstaging in multivariable logistic regression analysis (OR 12.9 95% CI 3.6-46.6, p<0.001). Histological factors of VI, LI and PNI are markers of aggressive disease and may have a role in prognostication and decision-making prior to treatment. The presence of LI as an independent marker of upstaging could be a potential indication for the use of neoadjuvant treatment in patients with early clinical disease.

Safety and efficacy of tislelizumab plus chemotherapy versus chemotherapy alone as neoadjuvant treatment for patients with locally advanced gastric cancer: real-world experience with a consecutive patient cohort.

Immunotherapy plus chemotherapy has recently been applied in the neoadjuvant treatment for locally advanced gastric cancer (LAGC), while its superiority over neoadjuvant chemotherapy (NACT) alone remains to be explored. This study explored the safety and efficacy of NACT plus tislelizumab in patients with LAGC. The data on patients with LAGC who received NACT combined with radical gastrectomy and NACT plus tislelizumab followed by radical gastrectomy was retrospectively collected. Clinicopathological characteristics of the two groups were compared. A total of 119 and 50 patients with gastric cancer treated with NACT and NACT plus tislelizumab, respectively, were enrolled. No significant difference was found between the baseline data of the two groups. The operative time (210.5 ± 70.4min vs. 237.6 ± 68.4min, P=0.732), intraoperative blood loss (157.8 ± 75.9ml vs. 149.1 ± 92.5ml, P=0.609), and number of dissected lymph nodes (24.7 ± 9.3 vs. 28.1 ± 10.3, P=0.195) was not statistically different between the two groups. In comparison to the NACT plus tislelizumab group, the R0 resection rate (100% vs. 89.9%, P=0.019) and pathologic complete response rate (26.0% vs. 3.4%, P<0.001) were significantly lower in the NACT group. The postoperative complication rates were 24.4% and 26.0% in the NACT and NACT plus tislelizumab groups with no significant difference (P=0.823). In subgroup analysis, tumor regression grade (TRG) (TRG 3: 72.3% vs. 23.5%, P<0.001) and ypN stage (stages 2-3: 46.8% vs. 5.9%, P=0.003) in the NACT group were significantly higher compared with the NACT plus tislelizumab group in esophagogastric junction carcinoma. Compared with the S-1 and oxaliplatin (SOX) or 5-fluorouracil, folinic acid, and oxaliplatin (FOLFOX) NACT regimen, NACT plus tislelizumab significantly improved the efficacy and R0 resection rate of LAGC without increasing the incidence of perioperative complications, particularly in esophagogastric junction carcinoma.

Neoadjuvant Androgen Receptor Signaling Inhibitors before Radical Prostatectomy for Non-Metastatic Advanced Prostate Cancer: A Systematic Review.

(1) Background: Several phase II studies, including randomized controlled trials (RCTs), assessed the efficacy of adding androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) as a neoadjuvant treatment in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). Summarizing the early results of these studies could help in designing phase III trials and patient counseling. (2) Methods: We queried three databases in January 2023 for studies that included PCa patients treated with neoadjuvant ARSI-based combination therapy before RP. The outcomes of interest were oncologic outcomes and pathologic responses, such as pathologic complete response (pCR) and minimal residual disease (MRD). (3) Results: Overall, twenty studies (eight RCTs) were included in this systematic review. Compared to ADT or ARSI alone, ARSI + ADT was associated with higher pCR and MRD rates; this effect was less evident when adding a second ARSI or chemotherapy. Nevertheless, ARSI + ADT resulted in relatively low pCR rates (0-13%) with a high proportion of ypT3 (48-90%) in the resected specimen. PTEN loss, ERG positive, or intraductal carcinoma seem to be associated with worse pathologic response. One study that adjusted for the effects of possible confounders reported that neoadjuvant ARSI + ADT improved time to biochemical recurrence and metastasis-free survival compared to RP alone. (4) Conclusions: Neoadjuvant ARSI + ADT combination therapy results in improved pathologic response compared to either alone or none in patients with non-metastatic advanced PCa. Ongoing phase III RCTs with long-term oncologic outcomes, as well as biomarker-guided studies, will clarify the indication, oncologic benefits, and adverse events of ARSI + ADT in patients with clinically and biologically aggressive PCa.

IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma.

Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, hampering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies.

Choice of the optimal metastatic lymph node marking in patients with breast cancer

Often, neoadjuvant treatment in patients with locally advanced breast cancer leads to complete clinical and pathomorphological regression of not only the primary tumor, but metastatic lymph nodes also. Currently, discussions are ongoing regarding the optimal volume of surgical intervention on regional lymph nodes in this category of patients. As a de-escalation of classical lymphadenectomy, a method of targeted axillary dissection (TAD) is used, which presumes a biopsy of sentinel lymph nodes (SLN) with the removal of a previously marked metastatic lymph node. Our study is aimed at choosing the most optimal method for labeling a metastatic lymph node. The study included 63 patients diagnosed with stage T1–3N1M0 breast cancer, all divided into two comparison groups: 29 patients had a radiopaque label placed in the metastatic lymph node before neoadjuvant therapy, and 33 patients had a radioisotope label (with I125).After the neoadjuvant treatment completion, all patients with complete clinical response in the lymph nodes underwent targeted axillary lymphadenectomy. We evaluated the time of the surgical intervention, the length of the skin incision, the presence of complications when using one or another type of marking. Based on the results of statistical analysis, we propose a variant with a radioisotope label for implementation into the clinical practice. This method, in our opinion, presented the best qualities, reliability and convenience for the surgeon, comfort for the patient.

Abstract ED11-1: Hormone receptor positive breast cancer

Abstract Estrogen receptor (ER) positive breast cancer is a heterogeneous group of diseases. While the major goal of neoadjuvant treatment in patients with locally advanced disease is to downstage the cancer to facilitate resectability and breast-conserving surgery, there is increasing evidence that response in the neoadjuvant setting has prognostic implications in predicting long term relapse outcomes. However, questions remain as to strategies that optimize neoadjuvant treatment selection of endocrine therapy versus chemotherapy, and whether adjuvant therapy could be tailored based on treatment response in the neoadjuvant setting. In this lecture, we will discuss evolving data regarding pathologic and molecular characteristics of ER positive breast cancer that assist with treatment selection in the neoadjuvant setting and the potential role of pathologic and biomarker response to neoadjuvant endocrine therapy in tailoring adjuvant chemotherapy decisions. Citation Format: Cynthia Ma. Hormone receptor positive 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 ED11-1.

Abstract P5-02-09: Quantitative analysis of fiber-level collagen features in H&amp;E whole-slide images predicts neoadjuvant therapy response in patients with HER2+ breast cancer

Abstract Background: Neoadjuvant treatment (NAT) combining chemotherapy and HER2-targeted agents is frequently administered to HER2-positive (HER2+) breast cancer (BC) patients, with some experiencing a pathological complete response (pCR) and others having residual disease measured by the residual cancer burden (RCB) score. Here, we use a physics-guided machine learning (ML)-based approach to extract fiber-level collagen features from hematoxylin and eosin (H&amp;E)-stained whole slide images (WSIs) and identify collagen-related associations with treatment response in HER2+ patients receiving NAT. Methods: Clinical data and specimens from stage II-III HER2+ BC patients enrolled on the De-escalation to Adjuvant Antibodies Post-pCR to Neoadjuvant THP (DAPHNe; NCT03716180) clinical trial and treated with neoadjuvant paclitaxel/trastuzumab/pertuzumab were analyzed. An ML-based model trained to identify regions of BC tissue as invasive carcinoma, ductal carcinoma in situ (DCIS), diffuse inflammatory infiltrate, stroma, necrosis, or normal tissue was deployed on WSIs of H&amp;E-stained diagnostic core needle biopsies (N=89) to generate tissue overlays. Additional tissue areas were computed from the tissue model predictions using heatmap transformation, including tumor nests (continuous regions predicted as invasive cancer epithelium or DCIS), tumor nest borders (stromal region boundaries 10 μm from tumor nests), and bulk tumor borders (stromal region boundaries 300 μm from aggregated tumor nests). A separate ML-based model trained to identify fiber-level collagen features in WSIs of H&amp;E-stained specimens was also deployed to generate collagen overlays. A fiber feature extraction pipeline was utilized to characterize properties of all identified collagen fibers in the WSI (on the order of hundreds of thousands per slide), including length, width, tortuosity, and angle. These fiber features were then assessed based on their position within the tumor (e.g. relative to the tumor nest border). Combinatorial features (e.g. angle of fibers with respect to tumor boundary) were then explored univariately for associations (N=609) with treatment response. Patients with pCR (RCB=0; N=53) were considered responders, while all other cases (RCBI-III; N=36) were designated non-responders. Due to the small size of the cohort analyzed here, raw p-values are reported. Results: Using estrogen receptor status as a clinical covariate, a logistic regression-based univariate analysis of 609 collagen-associated features revealed six features to strongly associate with pCR (p&amp;lt; 0.05, AUC≥0.75; Table 1). Notable feature themes were identified: 1) fiber tortuosity in tumor nest borders and tumor borders, 2) angle of fibers in tumor border with respect to tumor boundary, and 3) distribution patterns of fiber width in tumor nest borders. The presence of fibers perpendicular to tumor boundary tangents was negatively associated with pCR, as was higher fiber tortuosity and thickness in tumor nest borders. Conclusions: Improved prediction of response to NAT in patients with BC is needed to determine appropriate treatment strategies for each patient. Here, using ML-based models to identify tissue features and collagen fibers, we identify collagen-associated features, measured directly from WSIs of H&amp;E-stained diagnostic BC biopsies, that negatively correlate with pCR. Additional development of this strategy, including the addition of cell identification models and known clinical information, is underway to further refine this novel predictive model. Citation Format: Tan H. Nguyen, Mohammad Mirzadeh, Aaditya Prakash, Emma L. Krause, Jun Zhang, Michael Pyle, Esther R. Ogayo, Harry C. Cramer, Busem Binboga Kurt, Jacqueline Brosnan-Cashman, Michael G. Drage, Stuart Schnitt, Andrew H. Beck, Michael Montalto, Ilan Wapinski, Laura Chambre, Sara Tolaney, Adrienne Waks, Justin Lee, Elizabeth A. Mittendorf. Quantitative analysis of fiber-level collagen features in H&amp;E whole-slide images predicts neoadjuvant therapy response in patients with HER2+ 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 P5-02-09.

Abstract OT2-16-04: KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer: A single arm, multicenter, phase 2 study

Abstract Background: Despite the use of targeted therapy has revolutionized the treatment in the neoadjuvant setting for early, locally advanced, HER2-positive breast cancer, these approaches still have limited efficacy, which calls for persistent exploration for optimized treatment strategy. KN026 is a bispecific monoclonal antibody that targets the distinct extra-cellular domains II (Pertuzumab binding site) and IV (Trastuzumab binding site) of HER2. KN026 has better anti-tumor activity than either Trastuzumab or Pertuzumab used alone, and also aimed to demonstrate similar or better anti-tumor response than Trastuzumab in combination with Pertuzumab. Here we report the preliminary results of KN026 and docetaxel as neoadjuvant treatment in patients with HER2-positive early or locally advanced breast cancer (LABC). Methods: Treatment naive patients with HER2-positive early (T1c or 2, N1, M0; T2 or 3, N0, M0) or locally advanced breast cancer (T1c or 2 or 3, N2, M0; T3N1M0; T1c or 2 or 3, N3a or 3b, M0) were enrolled to receive 4 cycles of KN026 (30mg/kg, ivgtt d1, q3w) and docetaxel (75 mg/m2 ivgtt d1, q3w) neoadjuvant treatment. The primary endpoint was total pCR rate (tpCR; defined as absence of any residual invasive cancer in the breast and lymph nodes) [ypT0/is, ypN0]). Secondary endpoints were pCR in the breast (bpCR, defined as absence of any residual invasive cancer in the breast [ypT0/is]), ORR (objective response rate), safety, PK (pharmacokinetics) and immunogenicity. The study is still ongoing, and the planned enrollment number is 30. This study is registered in ClinicalTrials.gov, number NCT04881929. The data cutoff date was April 15, 2022. Results: Between August 8, 2021, and April 15, 2022, a total of 15 patients were enrolled from 5 sites. 7 (46.7%) patients were stage II, and 8 (53.3%) patients were stage III; 12 (80%) patients with lymph node metastases, and 3 (20%) patients without lymph node metastases; 7 (46.7%) patients were hormone receptor positive, and 8 (53.3%) patients were hormone receptor negative. As of April 15, 2022, 4 patients are still under neoadjuvant therapy, 1 patient withdrew from the study earlier due to AE during neoadjuvant treatment period, and 10 patients completed the surgery. Of the 10 patients who completed surgery, tpCR rate were 50% (5/10, 95% CI: 18.7%-81.3%), bpCR rate were 50% (5/10, 95% CI:18.7%-81.3%), and ORR were 100% (10/10, 95% CI: 69.2%-100%). The incidence of TRAE and Grade ≥3 TRAEs were 100% (15/15) and 53.3% (8/15) respectively. The most common TRAE were alopecia (14/15, 93.3%), white blood cell decreased (10/15, 66.7%), anemia (10/15, 66.7%), diarrhea (9/15, 60.0%), neutrophil count decreased (9/15, 60.0%), alanine aminotransferase increased (8/15, 53.3%) and hypoalbuminemia (8/15, 53.3%). The Grade ≥3 TRAE include neutrophil count decreased (8/15, 53.3%), white blood cell decreased (5/15, 33.3%), alanine aminotransferase increased (1/15, 6.7%), and lymphocyte count decreased (1/15, 6.7%). No Grade 5 TRAEs occurred. 3 TRAEs (Alanine aminotransferase increased, blood bilirubin increased and neutrophil count decreased) leading to KN026 interruption, and no TRAE leading to KN026 discontinuation. 1 SAE (hepatitis E-not TRAE; outcome: recovered) occurred in 1 patient, without other SAE or death throughout the study. Conclusions: KN026 and docetaxel as neoadjuvant treatment has shown promising clinical benefit for patients with HER2-positive early or locally advanced breast cancer with an acceptable and manageable safety profile. Further validation in a large-scale randomized controlled trial is warranted. Citation Format: Jiong Wu, Benlong Yang, Linxiaoxi Ma, Mingliang Zhang, Kun Wang, Yiding Chen, Zhimin Fan, Jing Zhang, Summer Xia. KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer: A single arm, multicenter, phase 2 study [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 OT2-16-04.

INFINITY: A multicentre, single-arm, multi-cohort, phase II trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability-high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC).

358 Background: In resectable GAC/GEJAC, MSI status is associated with better survival and potential lack of benefit from chemotherapy. Given the high responsiveness of MSI tumors to immunotherapy, neoadjuvant or definitive dual CTLA-4/PD(L)-1 inhibition may allow omission of chemotherapy or surgery. Methods: INFINITY is a multicentre, single-arm, multi-cohort phase II trial (NCT04817826) investigating the activity and safety of tremelimumab+durvalumab as neoadjuvant (Cohort 1) or definitive (Cohort 2) treatment for MSI, mismatch repair deficient (dMMR) and EBV-negative resectable GAC/GEJAC. In Cohort 1, patients (pts) received a 12-week treatment with single high dose tremelimumab 300 mg and durvalumab 1500 mg q4 weeks (T300/D) for 3 cycles followed by surgery. The primary endpoint was pCR rate (ypT0N0) with negative ctDNA after T300/D. Secondary endpoints: disease-free survival, overall survival, quality of life. Exploratory: correlation of pCR with clinical variables, PDL-1 CPS assessed by IHC 22C3, tumor mutational burden (TMB) by Foundation One, liquid biopsies and other biomarkers. Cohort 2 investigates non operative management after same treatment regimen. Results: Overall, 18 pts with MSI/dMMR resectable cT2-4 any N GAC/GEJAC were recruited in Cohort 1. One withdrew consent and 2 achieved a complete clinical-pathological response at radiology and endoscopy (ongoing) and refused surgery. Among 15 evaluable patients, 1 had disease progression and 14 underwent resection. pCR rate was 60% (9/15) and major-complete pathological response (&lt;10% viable cells) was 80%. All pts with pCR had negative ctDNA status pre-surgery. pCR rate was 1/6 (17%) in T4 vs 8/9 (89%) in T2-3 tumors (p=0.011), whereas no correlation was found with baseline N status. PDL-1 CPS was not associated with outcomes and TMB had a non-significant trend of correlation with pCR (median TMB 26 in non-pCR vs 40 in pCR group, p=0.2). Grade≥3 immune-related AEs occurred in 3 pts of safety population (n=18): colitis, pneumonitis, liver toxicity, all resolved with high dose steroids and did not impair surgery. Two pts died after surgery for other reasons than disease or AEs, whereas no disease relapses were observed in remaining pts. QoL and additional translational analyses on RNA-seq, digital spatial profiling and ctDNA monitoring will be presented. Conclusions: Pre-operative T300/D for 3 months was safe and provided promising proof of efficacy in MSI, dMMR GAC/GEJAC pts. These results open the way to investigate NOM in pts with clinical, pathological and molecular (ctDNA minimal residual disease) complete response after T300/D. Enrollment in Cohort 2 has started after IDMC evaluation and protocol. amendment to include only pts with cT2-3 tumors confirmed at staging laparoscopy. Clinical trial information: NCT04817826 .

Interpretation of Rectal MRI after Neoadjuvant Treatment in Patients with Rectal Cancer

MRI is currently the imaging modality of choice to evaluate rectal cancer after neoadjuvant treatment. The purposes of restaging MRI are to assess the resectability of rectal cancer and to decide whether organ preservation strategies can be applied in patients with a complete clinical response. This review article indicates the key MRI features needed to evaluate rectal cancer after neoadjuvant treatment using a systematic approach. Assessment of primary tumor response including MRI findings to predict a complete response is discussed. Additionally, MRI evaluation of the relationship between the primary tumor and adjacent structures, lymph node response, extramural venous invasion, and tumor deposits after neoadjuvant treatment is presented. Knowledge of these imaging features and their clinical relevance may help radiologists provide an accurate and clinically valuable interpretation of restaging rectal MRI.

ASCO 2022 Breast Cancer Updates

"Data presented at ASCO 2022 provide new perspectives of therapy for patients with breast cancer. Starting with the plenary session with DESTINY-Breast04 we are turning a new page in the treatment of metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer patients. The results of the DESTINY-Breast04 trial open a new therapeutic option for half of the patients with metastatic breast cancer, establishing HER2-low metastatic breast cancer as a targetable population with trastuzumab deruxtecan. The indications for antibody drug conjugates are expanding to patients with metastatic hormone receptor positive endocrine resistant disease based on TROPICS-02. From the multitude of clinical trials with antibody drug conjugates, we can envision that this will be likely the new way to deliver chemotherapy in the future. Differences in survival within the three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in upfront metastatic hormone positive breast cancer are emerging. We have data on continuation of ribociclib beyond disease progression on CDK4/6 in the MAINTAIN trial. The FAKTION trial does prove the benefit of the AKT inhibitor capivasertib and does highlight the importance of an extended molecular panel of the phosphatidylinositol3-kinase PI3K pathway. Furthermore, the exploratory analysis of KEYNOTE- 522, examining the correlation of event free survival and residual cancer burden after neoadjuvant treatment in patients with triple negative breast cancer does demonstrate a benefit of pembrolizumab extending to patient which did not achieve pathologic complete response, mainly by a decrease in residual cancer burden. Advances in biomarkers of response to immunotherapy are needed. For early stage breast cancer studies are in support of de-escalation of radiotherapy for low risk breast cancer patients and confirming the lack of benefit of adjuvant chemotherapy for elderly patients, even with high genomic grade index."

135O A multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced MIBC

Bladder cancer with HER2 high expression is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy. For HER2 positive MIBC, the efficacy of cisplatin- based NAC are unsatisfied. This study aims to evaluate the safety and efficacy of RC48-ADC, an anti-HER2 antibody conjugation, and tislelizumab as a novel neoadjuvant treatment in this population.

Validation of the KELIM score as a predictor of response to neoadjuvant treatment in patients with advanced high grade serous ovarian cancer

ObjectiveThe objective of this study is to externally validate the KELIM (rate of elimination of CA-125 elimation) score in patients with high grade serous ovarian cancer(HGSC)undergoing NACT and determine its relation to outcome of cytoreduction, platinum sensitivity, progression free(PFS) and overall survival(OS). MethodsThis is a retrospective cohort study of patients with Stage III-IV HGSC diagnosed between January 1, 2010 and December 31, 2019 and treated with NACT. KELIM score was calculated using at least 3 CA-125 values within the first 100 days of chemotherapy. Demographic parameters were collected and Kaplan Meier survival analyses were performed for PFS and OS. This study was approved by local ethics board. Results217 patients met inclusion criteria. Median follow-up was 28.93 months(range 2.86–135.06). There was no significant difference in stage, functional status, cytoreductive outcome or BRCA status(germline or somatic) between patients with a KELIM ≥ 1 and <1. Patients with a KELIM<1 had a lower median PFS (13.58 vs 19.69, p < 0.001), median platinum free interval(PFI) (7.66 vs 13.64, p < 0.001) and 5-year OS (57% vs 72%, p = 0.0140) compared to patients with KELIM≥1 . After adjusting for stage, treatment delays, bevacizumab or poly adenosine diphosphate-ribose polymerase(parp)-inhibitor use, and BRCA status, patients with KELIM<1 had a high risk of disease progression(HR = 1.57 (95% CI 1.08–2.28) and death(HR = 1.99 (95% CI 1.01–3.95) compared to KELIM≥1. BRCA status was independently associated to an increase on KELIM score (OR = 1.917, 95% CI 1.046–3.512, p = 0.035). ConclusionPatients with advanced HGSC undergoing NACT with a KELIM <1 were more likely to have platinum-resistant disease, worse PFS and worse OS when compared to patients with KELIM≥1. The KELIM score can be a helpful tool to predict chemo-response and aid in treatment decision making.

Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial

BackgroundNeoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC.Materials and methodsA total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate.ResultsThe incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR.ConclusionTriweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC.Trial registrationChinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570

Real-world study of trastuzumab and pertuzumab combined with chemotherapy in neoadjuvant treatment for patients with HER2-positive breast cancer.

Clinical trials have shown that trastuzumab (H) and pertuzumab (P) combined with chemotherapy as neoadjuvant therapy increased pathological complete response (pCR) rate of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, date in China in the real world are currently limited.Clinical data from patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy at 2 institutions from March 2019 to February 2022 were retrospectively analyzed. Adverse reactions were evaluated using CTCAE version 5.0. The primary endpoint was total pathologic complete response (tpCR; ypT0/isypN0), and the secondary endpoints were breast pathologic complete response (bpCR; ypT0/is) and axillary pathologic complete response (apCR; ypN0). Factors influencing tpCR were also analyzed.A total of 302 patients were included in the analysis, of which 145 were treated with H + P + taxane + carboplatin (TcbHP), 94 with H + P + taxane (THP) and 63 with sequential anthracycline and cyclophosphamide, followed by H + P + taxane (AC-THP). The overall tpCR rate was 64.9%, and those of TcbHP, THP, and AC-THP were 73.1%, 52.1%, and 65.1%, respectively. The tpCR rate of the hormone receptor (HR) negative group (80.3%) was higher than that of the HR positive group (52.1%). The overall bpCR rate was 73.5% and the apCR rate was 75.8%. In the univariate analysis, HR, HER2 status and treatment regimen were related factors that affected tpCR. In the multivariate analysis, HR, HER2 status and treatment regimen were independent predictors of tpCR (P < .001, P < .001 and P = .009). The levels 3 and 4 toxicities rates of TcbHP were slightly higher than those of THP and AC-THP.HP combined with chemotherapy has achieved a high pCR rate. The TcbHP regimen had the highest pCR. HR-negative tumors demonstrated a higher pCR. HR, HER2 status and treatment regimen were independent predictors of tpCR. The adverse reactions are controllable.

Controlling Nutritional Status Score Serves as a Prognosticator in Esophageal Squamous Cell Carcinoma: Optimal Timing of Evaluation of Patients Undergoing Neoadjuvant Treatment.

Usefulness of various nutritional indices for management of patients with esophageal squamous cell carcinoma (ESCC) has been reported. Although Controlling Nutritional Status (CONUT) score is among promising indices to predict outcome, the optimal timing for its measurement during the perioperative period remains unknown. Here the prognostic value of the CONUT score was assessed among patients with ESCC. We analyzed 464 patients who underwent subtotal esophagectomy of ESCC, of which 276 patients were treated with neoadjuvant treatment (NAT). The significance of the associations between candidate parameters including the CONUT score and postoperative prognosis were evaluated. Among the 25 candidate predictors, the preoperative CONUT score had the highest correlation with overall survival (OS) after surgery. Patients were categorized as follows: normal, mild, and moderate or severe, on the basis of the preoperative CONUT score. OS was significantly shortened as the CONUT score worsened. Multivariable analysis revealed that the CONUT scores of the subgroups mild (Hazard ratio [HR] 1.69) and moderate or severe (HR 2.18) were independent predictors of poor prognosis for OS. Furthermore, in an analysis limited to patients who underwent NAT, OS was significantly shortened as the preoperative CONUT score worsened. On the contrary, there was no significant difference in RFS among patient groups stratified by the CONUT score determined before NAT. Our study indicates that the preoperative CONUT score serves as a prognosticator in resectable ESCC. The preoperative CONUT value was more useful than that before NAT in patients administered NAT.

Response to neoadjuvant treatment in patients with breast cancer from the Department of Medical Oncology of the Hospital de Clínicas

Response to neoadjuvant treatment in patients with breast cancer from the Department of Medical Oncology of the Hospital de Clínicas

168P Long-term survival of a randomised, open-label, phase II study comparing the efficacy and safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE)

The GENEVIEVE study (NCT01779479) compared the pathological complete response (pCR) rate in patients with operable triple-negative (TNBC) or luminal B/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) treated with either cabazitaxel or weekly paclitaxel. Primary analyses showed no short-term effect of cabazitaxel in TNBC or luminal B/HER2- primary BC, while there seemed to be no differences in drug exposure and patient compliance between the two arms (Kümmel et al. Eur J Cancer 2017).

Improving prediction of response to neoadjuvant treatment in patients with breast cancer by combining liquid biopsies with multiparametric MRI: protocol of the LIMA study – a multicentre prospective observational cohort study

IntroductionThe response to neoadjuvant chemotherapy (NAC) in breast cancer has important prognostic implications. Dynamic prediction of tumour regression by NAC may allow for adaption of the treatment plan before completion,...

Evaluation of the results of neoadjuvant treatment in patients with HER2 positive breast cancer subtype

Background. In women, breast cancer is the most common malignant tumor. Based on current clinical guidelines for HER2 positive tumor growth, it is possible to carry out preoperative chemotherapy for further organ-preserving operations. However, a prognostic scale for assessing neoadjuvant treatment has not yet been developed.&#x0D; Aim. To create a mathematical model on the basis of which a computer program was developed to determine the likelihood of the neoadjuvant treatment effectiveness in patients diagnosed with HER2 positive breast cancer for further organ-preserving operations.&#x0D; Material and methods. A planned retrospective study was performed at the Samara Regional Clinical Oncology Dispensary to assess the results of combined treatment of 93 patients diagnosed with breast cancer with HER2-positive tumor growth subtype with organ-preserving operations. The age of the patients was from 31 to 62 years, the mean age was 47.119.78 years. Three (15.53%) patients were diagnosed with stage I of the disease according to the TNM system, and 90 (84.47%) with stage II. A search for statistically significant predictors of achieving morphological regression as a result of preoperative chemotherapy was carried out.&#x0D; Results. The mathematical model was created in the logistic regression module according to Wald's algorithm. Using SPSS 10.0, stepwise exclusion of predictors was performed. As a result of the multivariate analysis, a mathematical model and the corresponding program for the electronic computer Calculation of the achievement of complete morphological regression in patients diagnosed with primary operable breast cancer with epidermal growth factor receptors after neoadjuvant chemotherapy were created. In the future, the evaluation of the effectiveness of this program was compared with the results of 206 patients treatment.&#x0D; Conclusion. The creation of a mathematical model and a computer program made it possible to personalize the most effective treatment regimen for patients diagnosed with HER2 positive breast cancer, depending on the initial characteristics of the tumor.