Definition Of pCR Research Articles

An online tool using clinical factors to estimate the probability of partial clinical remission of adult-onset Type 1 diabetes

A type 1 diabetes (T1D) diagnosis is often followed by a period of reduced exogenous insulin requirement, with acceptable glucose control, called partial clinical remission (pCR). Various criteria exist to define pCR, which is associated with better clinical outcomes.We aimed to develop formulae and a related online calculator to predict the probability of pCR at 3- and 12-months post-T1D diagnosis.We analysed data from 133 adults at their T1D diagnosis (mean ± SD age: 27 ± 6 yrs., HbA1c 11.1 ± 2.0 %, 98 ± 22 mmol/mol), 3- and 12-months later. All patients were enrolled in the prospective observational InLipoDiab1 study (NCT02306005). We compared four definitions of pCR: 1) stimulated C-peptide >300 pmol/l; 2) insulin dose-adjusted HbA1c ≤9 %; 3) insulin dose <0.3 IU/kg/24 h; and HbA1c ≤6.4 % (46 mmol/mol); and 4) insulin dose <0.5 IU/kg/24 h and HbA1c <7 % (53 mmol/mol). Using readily available demographics and clinical chemistry data exhaustive search methodology was used to model pCR probability.There was low concordance between pCR definitions (kappa 0.10). The combination of age, HbA1c, diastolic blood pressure, triglycerides and smoking at T1D onset predicted pCR at 12-months with an area under the curve (AUC) = 0.87. HbA1c, triglycerides and insulin dose 3-mths post-diagnosis had an AUC = 0.89. A related calculator for pCR in adult-onset T1D is available at http://www.bit.ly/T1D-partial-remission.

Systematic Review of Nomograms Used for Predicting Pathological Complete Response in Early Breast Cancer.

Pathological complete response (pCR) is an important surrogate outcome to assess the effects of neoadjuvant chemotherapy (NAC). Nomograms to predict pCR have been developed with local data to better select patients who are likely to benefit from NAC; however, they were never critically reviewed regarding their internal and external validity. The purpose of this systematic review was to critically appraise nomograms published in the last 20 years (2010-2022). Articles about nomograms were searched in databases, such as PubMed/MEDLINE, Embase and Cochrane. A total of 1120 hits were found, and seven studies were included for analyses. No meta-analysis could be performed due to heterogeneous reports on outcomes, including the definition of pCR and subtypes. Most nomograms were developed in Asian centers, and nonrandomized retrospective cohorts were the most common sources of data. The most common subtype included in the studies was triple negative (50%). There were articles that included HER2+ (>80%). In one study, scholars performed additional validation of the nomogram using DFS and OS as outcomes; however, there was a lack of clarity on how such endpoints were measured. Nomograms to predict pCR cannot be extrapolated to other settings due to local preferences/availability of NAC. The main gaps identified in this review are also opportunities for future nomogram research and development.

1282-P: Interactive Tool to Estimate Probability of Partial Clinical Remission in Adult-Onset Type 1 Diabetes

Introduction: Type 1 diabetes (T1D) diagnosis is often (in adults) followed by a (‘honeymoon’) period of reduced insulin need, also called partial clinical remission (pCR), which is associated with better outcomes. Various definitions of pCR exist. Aim: To create an online calculator to predict probability of pCR in adult-onset T1D 12-mths post-diagnosis. Methods: We analysed data from 133 adults at T1D diagnosis (mean±SD age: 27±6, HbA1c: 11.1±2.0%, BMI: 22.5±3.7 kg/m2), 3-mths and 12-mths later. All were enrolled in the prospective observational InLipODiab (NCT02306005) study. We used 4 definitions for pCR 12-mths post-diagnosis: 1) insulin dose-adjusted HbA1c≤9%; 2) insulin dose&amp;lt;0.3U/kg/24h and HbA1c≤6.4%; 3) insulin dose&amp;lt;0.5U/kg/24h and HbA1c&amp;lt;7%; 4) stimulated C-peptide &amp;gt;300pmol/L. Exhaustive search was used to find the best models (based on AIC) based on usually available data at diagnosis and 3-mths. Calculator (Figure 1) available at http://www.bit.ly/T1D-partial-remission. Results: There was low concordance between pCR definitions (Cohen’s weighted kappa 0.01-0.61.) Combination of age, HbA1c, diastolic BP, triglycerides and smoking at T1D onset predicted pCR (12-mths) with AUC=0.84. HbA1c, triglycerides and insulin dose 3-mths post-diagnosis had an AUC=0.89. Conclusion: A new online calculator can predict pCR in adult-onset T1D for clinical and research use. Disclosure A.Grzelka-wozniak: None. A.S.Januszewski: None. J.Flotynska: None. A.Jenkins: Advisory Panel; Insulet Corporation, Board Member; Insulin for Life, Research Support; Abbott Diabetes, Medtronic, Hemsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), National Institutes of Health. D.Zozulinska-ziolkiewicz: Advisory Panel; Abbott, Lilly, Lilly, Novo Nordisk, Medtronic, Speaker's Bureau; Abbott, Ascensia Diabetes Care, Novo Nordisk, Medtronic, Boehringer-Ingelheim, AstraZeneca. A.Uruska: Other Relationship; Lilly, Boehringer-Ingelheim, AstraZeneca, Ascensia Diabetes Care, Sanofi.

Re-Evaluation of Pathologic Complete Response as a Surrogate for Event-Free and Overall Survival in Human Epidermal Growth Factor Receptor 2-Positive, Early Breast Cancer Treated With Neoadjuvant Therapy Including Anti-Human Epidermal Growth Factor Receptor 2 Therapy.

Pathologic complete response (pCR) has prognostic importance and is frequently used as a primary end point, but doubts remain about its validity as a surrogate for event-free survival (EFS) and overall survival (OS) in human epidermal growth factor receptor 2 (HER2)-positive, early breast cancer. We obtained individual-patient data from randomized trials of neoadjuvant anti-HER2 therapy that enrolled at least 100 patients, had data for pCR, EFS, and OS, and a median follow-up of at least 3 years. We quantified the patient-level association between pCR (defined as ypT0/Tis ypN0) and both EFS and OS using odds ratios (ORs, with ORs >1.00 indicating a benefit from achieving a pCR). We quantified the trial-level association between treatment effects on pCR and on EFS and OS using R2 (with values above 0.75 considered as indicating strong associations). Eleven of 15 eligible trials had data for analysis (3,980 patients, with a median follow-up of 62 months). Considering all trials, we found strong patient-level associations, with ORs of 2.64 (95% CI, 2.20 to 3.07) for EFS and 3.15 (95% CI, 2.38 to 3.91) for OS; however, trial-level associations were weak, with an unadjusted R2 of 0.23 (95% CI, 0 to 0.66) for EFS and 0.02 (95% CI, 0 to 0.17) for OS. We found qualitatively similar results when grouping trials according to different clinical questions, when analyzing only patients with hormone receptor-negative disease, and when using a more stringent definition of pCR (ypT0 ypN0). Although pCR may be useful for patient management, it cannot be considered as a surrogate for EFS or OS in neoadjuvant trials of HER2-positive, operable breast cancer.

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial

Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. The presence of DCIS and EFS, DRFS, and LRR. The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. ClinicalTrials.gov Identifier NCT01042379.

Neoadjuvant pertuzumab in non‑metastatic HER2‑positive breast tumors: Multicentric study in Peru (NeoHer)

Several clinical trials have demonstrated the benefit of adding pertuzumab to trastuzumab plus neoadjuvant chemotherapy in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The comparison of outcomes between nonrandomized groups of patients who received similar treatments in routine practice remains difficult. The present study aimed to evaluate the pathological complete response (pCR) rates achieved with pertuzumab among patients in routine clinical care in Peru using real-world data. The definition of pCR used was the absence of residual invasive cancer from the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. A total of 44 patients with non-metastatic HER2-positive breast cancer (stages II and III) treated with pertuzumab in the neoadjuvant setting and who underwent surgery at three private clinics in Lima (Peru) were retrospectively evaluated. The pCR was the efficacy endpoint and it was determined and compared with the results from other clinical trials. Furthermore, safety data were described. The median age was 44 years (interquartile range, 39.5-50.5 years) and 65.9% of patients were premenopausal. Regarding the clinical stage, 56.8% were IIA/IIB and 36.4% were IIIA/IIIB/IIIC. All treatment schemes included concurrent trastuzumab. The patients' treatment comprised neoadjuvant therapy of docetaxel/trastuzumab/pertuzumab (THP) with a median of 4 cycles in 30 patients (68.2%) or docetaxel/trastuzumab/pertuzumab/carboplatin (THPCarb) with a median of 6 cycles in 14 patients (31.8%). In total, 70.5% of patients experienced pCR; among hormone receptor-negative cases, 75.0% achieved pCR and in tumors expressing hormone receptors, the rate of pCR was 66.7%. Of those patients subjected to neoadjuvant treatment with THP, 66.7% (20/30) achieved pCR, whereas 78.6% (11/14) of patients who received THPCarb had a pCR. The incidence of drug-related adverse events was 59.1% and in none of the patients, administration was discontinued due to toxicity. The present results of Peruvian patients with HER2 breast cancer treated according to clinical routine demonstrated that dual blockade of HER2 with trastuzumab and pertuzumab in the neoadjuvant setting achieved high rates of pCR even in hormone receptor-positive patients. These results are consistent with those of randomized controlled trials, with a good safety profile.

The percentage of residual DCIS in patients diagnosed with primary invasive breast cancer treated with neoadjuvant systemic therapy: A nationwide retrospective study

IntroductionNeoadjuvant systemic therapy (NST) is increasingly applied in breast cancer to improve surgical and oncological outcome. Approximately 21% of patients receiving NST achieve pathological complete response (pCR) of the breast. There is disagreement on the definition of pCR with respect to residual DCIS (ypT0 versus ypT0/is). The aim of this retrospective study was to determine the percentage of breast pCR (ypT0) and residual DCIS (ypTis), and its association with clinicopathological variables, in patients treated with NST and surgery. Materials and methodsPatients with invasive breast cancer treated with neoadjuvant chemotherapy, with or without targeted therapy, in the period of 2010–2019 were selected from the Netherlands Cancer Registry (NCR). Descriptive statistics and multivariable logistic regression analyses were used to analyse the percentage of ypT0 and ypTis and its association with clinicopathological variables. ResultsFrom the NCR database, 20495 patients were included, of whom 5847 (28.5%) achieved breast pCR (ypT0) and 881 (4.3%) showed residual DCIS (ypTis). The percentage of ypTis was highest in HER2+ tumour subtypes (ER+HER2+ 7.9%, ER-HER2+ 9.8%, ER+HER2- 2.1%, triple negative 3.3%, p < 0.001). Multivariable logistic regression analyses demonstrated high tumour grade (OR 2.00, p = 0.003) and HER2+ tumour subtype (ER+HER2+ OR 3.58, ER-HER2+ OR 4.37, p < 0.001) as independent predictors for ypTis. ConclusionpCR (ypT0) was achieved in 5847 (28.5%) patients receiving NST and residual DCIS (ypTis) was found in 881 (4.3%) patients. Consequently, the rate of pCR may be affected by ypTis when not excluded from the definition. The percentage of ypTis is highest in HER2+ subtypes.

A narrative review of primary research endpoints of neoadjuvant therapy for lung cancer: past, present and future.

ObjectiveThis review summarizes the current status of neoadjuvant therapy and discusses the choice of new clinical research endpoints for non-small cell lung cancer.BackgroundNeoadjuvant chemotherapy is a recognized practice in patients with resectable and locally advanced lung cancer. With the introduction of molecular targeted drugs and immune checkpoint inhibitors (ICIs), the overall survival (OS) of patients with lung cancer has been significantly improved, and the original traditional clinical research endpoints are no longer suitable for existing clinical research. In order to accelerate the process of clinical trials and the development and approval of drugs, it is necessary to find suitable alternative indicators as the main indicators of clinical research.MethodsTherefore, this article focuses on clinical trials using disease-free survival (DFS), progression free survival, and pathological evaluation indicators, pathologic complete response and major pathologic response, as surrogate endpoints. We search related literature through PubMed database and clinical trials through clinicaltrials.gov.ConclusionsPathologic complete response and major pathologic response are recommended as surrogate endpoints in the era of neoadjuvant immunotherapy, and secondary endpoints are listed for the prediction of pathological results. In addition, the definitions of major pathological response (MPR) and PCR should be standardized, and a new pathological evaluation standard should be developed, which is applicable to all current treatment methods.KeywordsNeoadjuvant therapy; resectable lung cancer; clinical research endpoint; pathological response

Diagnostic Accuracy of MRI in Evaluating Response After Neoadjuvant Systemic Therapy in Operable Breast Cancer.

BackgroundNeoadjuvant chemotherapy (NAC) is an important step in the treatment of various types of breast cancer by downsizing the tumor to make it operable. Determining disease extent after NAC is essential for accurate surgical planning. MRI has been the gold standard for detecting tumors that are usually difficult to detect on ultrasound or mammography. However, the use of MRI after NAC is controversial. Therefore, we aimed to evaluate the diagnostic accuracy of post-NAC MRI in the detection of residual disease preoperatively and to investigate the factors associated with pathological complete response (pCR).MethodologyThis retrospective review study was approved by the institutional review board with waiving of the informed consent. A total of 90 charts between January 2016 and January 2019 were reviewed. Baseline lesion size was measured as the maximal diameter in a single dimension by pretreatment MRI. To assess the diagnostic accuracy of MRI in detecting residual disease, we used two different definitions of pCR in the breast. The first is the resolution of both invasive disease and ductal carcinoma in situ. The second is the resolution of the invasive disease only. As a secondary objective of the study, we assessed the association between different patients’ characteristics and both MRI and pathologic response using univariate and multivariate analysis.ResultsA total of 52 women (mean age: 47.4 years; range: 28-74) with 56 breast masses were eligible for the study. Complete MRI response was noted in 22 (39%) masses. pCR was achieved in 14 (25%) and 25 (44.6%) masses using the first and second pCR definitions, respectively. The negative predictive value (NPV) and overall accuracy of MRI for detecting residual disease were 50% and 75%, respectively, using the first pCR definition. With the second pCR definition, NPV and accuracy were 77.3% and 76.8%, respectively. Positive axillary lymph nodes were the only significant factor associated with incomplete MRI and pathological responses.ConclusionsMRI NPV for residual disease was higher with the second pCR definition; however, overall accuracy was not different. MRI accuracy in detecting residual disease after NAC is not adequate to replace pathological assessment.

Accuracy of Magnetic Resonance Imaging–Guided Biopsy to Verify Breast Cancer Pathologic Complete Response After Neoadjuvant Chemotherapy

After neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) is an optimal outcome and a surrogate end point for improved disease-free and overall survival. To date, surgical resection remains the only reliable method for diagnosing pCR. To evaluate the accuracy of magnetic resonance imaging (MRI)-guided biopsy for diagnosing a pCR after NAC compared with reference-standard surgical resection. Single-arm, phase 1, nonrandomized controlled trial in a single tertiary care cancer center from September 26, 2017, to July 29, 2019. The median follow-up was 1.26 years (interquartile range, 0.85-1.59 years). Data analysis was performed in November 2019. Eligible patients had (1) stage IA to IIIC biopsy-proven operable invasive breast cancer; (2) standard-of-care NAC; (3) MRI before and after NAC, with imaging complete response defined as no residual enhancement on post-NAC MRI; and (4) definitive surgery. Patients were excluded if they were younger than 18 years, had a medical reason precluding study participation, or had a prior history of breast cancer. Post-NAC MRI-guided biopsy without the use of intravenous contrast of the tumor bed before definitive surgery. The primary end point was the negative predictive value of MRI-guided biopsy, with true-negative defined as negative results of the biopsy (ie, no residual cancer) corresponding to a surgical pCR. Accuracy, sensitivity, positive predictive value, and specificity were also calculated. Two clinical definitions of pCR were independently evaluated: definition 1 was no residual invasive cancer; definition 2, no residual invasive or in situ cancer. Twenty of 23 patients (87%) had evaluable data (median [interquartile range] age, 51.5 [39.0-57.5] years; 20 women [100%]; 13 White patients [65%]). Of the 20 patients, pre-NAC median tumor size on MRI was 3.0 cm (interquartile range, 2.0-5.0 cm). Nineteen of 20 patients (95%) had invasive ductal carcinoma; 15 of 20 (75%) had stage II cancer; 11 of 20 (55%) had ERBB2 (formerly HER2 or HER2/neu)-positive cancer; and 6 of 20 (30%) had triple-negative cancer. Surgical pathology demonstrated a pCR in 13 of 20 (65%) patients and no pCR in 7 of 20 patients (35%) when pCR definition 1 was used. Results of MRI-guided biopsy had a negative predictive value of 92.8% (95% CI, 66.2%-99.8%), with accuracy of 95% (95% CI, 75.1%-99.9%), sensitivity of 85.8% (95% CI, 42.0%-99.6%), positive predictive value of 100%, and specificity of 100% for pCR definition 1. Only 1 patient had a false-negative MRI-guided biopsy result (surgical pathology showed <0.02 cm of residual invasive cancer). This study's results suggest that the accuracy of MRI-guided biopsy to diagnose a post-NAC pCR approaches that of reference-standard surgical resection. MRI-guided biopsy may be a viable alternative to surgical resection for this population after NAC, which supports the need for further investigation. ClinicalTrials.gov Identifier: NCT03289195.

Evaluación de la respuesta patológica a quimioterapia neoadyuvante en cáncer de mama: correlación con el fenotipo molecular

Introduction and objectiveBreast cancer can be classified into different molecular subtypes with important therapeutic and prognostic implications. Neoadjuvant chemotherapy (NAC) increases the possibility of performing conservative surgery and allows in vivo testing of the sensitivity of the tumor. Our aim was to evaluate the pathological response to NAC in relation to the molecular phenotype and the different definitions of the pathological response. Patients228 patients treated with NAC and subsequent surgery between 2012 and 2018 were selected from our breast cancer database. Molecular phenotypes were established based on the criteria of the St Gallen 2013 Conference. Pathological response was evaluated following Miller-Payne (breast) and Sataloff (axilla) classification systems. ResultsThe most frequent molecular phenotype was luminal B/HER2 negative (30.3%), followed by luminal B/HER2 positive (26.3%), triple negative (24.6%), HER2 positive (13.2%), and luminal A (5.7%). The rate of pathological complete response (pCR) was 35.5% in breast and 15.3% in axilla. The rate of pCR considering breast and axilla together was 26.8%. The molecular phenotype with the highest rate of pCR was HER2 positive (66.7%) followed by triple negative (30.4%), luminal B/HER2 positive (21.7%), luminal B/HER2 negative (14.5%), and luminal A (7.7%) (p < 0.001). The same results were found with the different definitions of pCR we evaluated. ConclusionsComplete pathological response to NAC in breast cancer depends largely on the molecular phenotype of the tumor, regardless of the definition of pCR, with the highest response rates in the breast and axilla in the HER2 positive and triple negative phenotypes.

Abstract P2-16-13: Meta-analysis of nanoparticle albumin-bound paclitaxel (Nab-PTX) used as a neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01)

Abstract [Background] Nanoparticle albumin-bound paclitaxel (Nab-PTX) is a novel taxane formulation that was developed to avoid Cremophor/ethanol associated toxicities such as peripheral neuropathy and hypersensitive reactions. Since Taxol plays an important role in breast cancer therapy, Nab-PTX is considered safe and effective for metastatic breast cancer (MBC). According to these reports, a regimen including Nab-PTX in a neoadjuvant setting may induce preferable results. Several recent reports using a combination of Nab-PTX and anthracycline in neoadjuvant chemotherapy (NAC) have been published. In Japan, at least 34 small phase II studies using a Nab-PTX regimen have been registered with the University hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR). We believe that integration of these data is important to evaluate the power of Nab-PTX, so we conducted a meta-analysis based on individual patient data (IPD). [Materials and Methods] This study is a collaborative meta-analysis of single arm trials using IPD to summarize the published and unpublished evidence of Nab-PTX-containing regimen efficacy. The main objective was to assess the rate of pathological complete response (pCR). Definitions of pCR were (1) ypT0 ypN0, (2) ypT0/is ypN0, and (3) ypT0/is ypNX. The secondary objectives were adverse events (AEs) (≥G3) and dose of administered Nab-PTX (mg/m2). First, we found 34 phase II studies registered from Feb 2011 to Jun 2016 using an electron search of UMIN-CTR. Second, we contacted each principal investigator (PI) to ask if they would participate in this study by providing individual data. Inclusion criteria were as follows: (1) Clinical trial(s) started after July 2010, (2) Principal investigator(s) in each trial agreed with study participation, (3) Nab-PTX-containing regimen was used for neoadjuvant chemotherapy in naive operable breast cancer patients, (4) Registered in UMIN with ethical review, (5) Clinical trials with more than 10 patients, (6) Completed clinical trials only were included (unpublished data are available), and (7) Each researcher was authorized by the research ethics committee to submit the data. pCR rates in all cases/each subtype were calculated with a 95% confidence interval (CI). The proportion of AEs and total Nab-PTX dose were also calculated. [Results] Among 34 studies, 16 studies (4 published, 12 unpublished) included 758 patients. Among these 16 studies, 5 (2 metastatic, 3 no treatment) were excluded for all analyses (n=753). After excluding 8 (3 declined surgery, 1 hospital transfer, 4 unknown), a total of 745 (including 2 PD, 1 death) were analyzed for the primary analysis. All HER2-positive cases were treated by combining Nab-PTX and trastuzumab. Crude overall percentages of pCR (ypT0ypN0, ypT0/isypN0, and ypT0/isypNX) were 18.1%, 26.0%, and 28.6%, respectively. In detail, 6.7%, 10.2%, and 13.4% for Luminal type (n=343), 26.3%, 31.5%, and 32.3% for triple negative (TNBC, n=232), 40.5%, 63.5%, and 68.9% for HER2-rich (n=74), 21.9%, 40.6%, and 42.7% for Luminal/HER2 type (n=96), respectively. AEs (≥G3) were observed as follows: 41.5% neutropenia, 32.3% leukopenia, 10.6% febrile neutropenia, 10.6% peripheral sensory neuropathy, 2.5% peripheral motor neuropathy, 6.4% myalgia, 5.5% arthralgia, 6.1% hepatobiliary disorders, 4.5% vomiting, 0.7%, cardiac disorders, and 0.9% infusion reaction. Only one patient died during FEC followed by Nab-PTX. [Conclusion] NAC regimen containing Nab-PTX was safe, and the efficacy was equal to or greater than regimens containing other taxanes. The combination Nab-PTX and trastuzumab is particularly useful and powerful against the HER2-positive subtype. However, the Nab-PTX-containing regimen is not as powerful against TNBC in a neoadjuvant setting. Citation Format: Manabu Futamura, Mari Oba, Norikazu Masuda, Hiroko Bando, Yutaka Yamamoto, Takanori Kin, Toshiaki Saeki, Takeshi Nagashima, Takashi Kuwayama, Uhi Toh, Akira Hirano, Masafumi Inokuchi, Kazuhiko Yamagami, Yutaka Mizuno, Yasuyuki Kojima, Takahiro Nakayama, Hiroyuki Yasojima, Morihito Okada, Shinji Ohno. Meta-analysis of nanoparticle albumin-bound paclitaxel (Nab-PTX) used as a neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-13.

Multiparametric MR imaging to assess response following neoadjuvant systemic treatment in various breast cancer subtypes: Comparison between different definitions of pathologic complete response

ObjectivesTo validate the performance of multiparametric magnetic resonance (MR) imaging to assess pathologic response to neoadjuvant systemic therapy (NST) in various breast cancer subtypes considering two definitions of pCR: absence of any residual invasive cancer or DCIS (ypT0) and absence of invasive tumour cells (ypT0/is). MethodsInstitutional review board–approved retrospective study, with waiver of the need to obtain informed consent. From January 2015 to June 2017, 81 women with 82 breast cancers undergoing NST were included. Eighteen lesions (22%) were immunohistochemically HER2-positive, 12 (15%) triple negative (TN), 42 (51%) luminal B-like and 10 (12%) luminal B-like/HER2-positive. Breast MR imaging was performed before and after NST. A comparative analysis considering pCR as ypT0 and ypT0/is was carried out. Performance of univariate and multivariate models to potentially predict pathologic response were evaluated. ResultsypT0 was attained in 23% (19/82) of cases and ypT0/is in 33% (27/82) of cases. In both scenarios, HER2-positive subtype achieved the best response, 53% and 48%, respectively. A significant relationship was found between late enhancement and pathologic response (p < 0.001) regardless of pCR definition. In the ypT0 scenario, mean ADC ratio in the pCR subgroup was significantly higher than that in the non-pCR subgroup (p = 0.021) but no significant relationship was noted in ypT0/is. A multivariate model including MR late enhancement, ADC ratio and tumor subtype identified pathologic response with 86% and 84% accuracy when ypT0 and ypT0/is were considered, respectively. ConclusionMR imaging late enhancement and ADC ratio along with breast cancer IHC subtype identify pathologic response following NST with high accuracy, achieving the highest NPV in TN and HER2-positive tumors and the highest PPV in luminal B-like subtypes, regardless of the definition of pCR as ypT0 or ypT0/is. In light of these findings and given that residual DCIS does not have an impact on survival rates, ypT0/is seems to be the preferable definition of pCR.

Cortical surface area abnormalities in young adolescents at ultra-high risk who later develop psychosis

To validate the performance of multiparametric magnetic resonance (MR) imaging to assess pathologic response to neoadjuvant systemic therapy (NST) in various breast cancer subtypes considering two definitions of pCR: absence of any residual invasive cancer or DCIS (ypT0) and absence of invasive tumour cells (ypT0/is).Institutional review board–approved retrospective study, with waiver of the need to obtain informed consent. From January 2015 to June 2017, 81 women with 82 breast cancers undergoing NST were included. Eighteen lesions (22%) were immunohistochemically HER2-positive, 12 (15%) triple negative (TN), 42 (51%) luminal B-like and 10 (12%) luminal B-like/HER2-positive. Breast MR imaging was performed before and after NST. A comparative analysis considering pCR as ypT0 and ypT0/is was carried out. Performance of univariate and multivariate models to potentially predict pathologic response were evaluated.ypT0 was attained in 23% (19/82) of cases and ypT0/is in 33% (27/82) of cases. In both scenarios, HER2-positive subtype achieved the best response, 53% and 48%, respectively. A significant relationship was found between late enhancement and pathologic response (p < 0.001) regardless of pCR definition. In the ypT0 scenario, mean ADC ratio in the pCR subgroup was significantly higher than that in the non-pCR subgroup (p = 0.021) but no significant relationship was noted in ypT0/is. A multivariate model including MR late enhancement, ADC ratio and tumor subtype identified pathologic response with 86% and 84% accuracy when ypT0 and ypT0/is were considered, respectively.MR imaging late enhancement and ADC ratio along with breast cancer IHC subtype identify pathologic response following NST with high accuracy, achieving the highest NPV in TN and HER2-positive tumors and the highest PPV in luminal B-like subtypes, regardless of the definition of pCR as ypT0 or ypT0/is. In light of these findings and given that residual DCIS does not have an impact on survival rates, ypT0/is seems to be the preferable definition of pCR.

‘Watch and wait’ in rectal cancer: summary of the current evidence

The management of rectal cancer has evolved considerably over the last few decades with increasing use of neoadjuvant chemoradiotherapy (nCRT). Complete clinical response (cCR) and even complete pathological response (pCR) have been noted in a proportion of patients who had surgery after nCRT. This raises the concern that we may have been 'over-treating' some of these patients and lead to an increasing interest in 'watch and wait' (W&W) approach for patients who had cCR to avoid the morbidity associated with rectal surgery. A review of the literature in English pertaining to rectal cancer in the context of W&W, organ preservation and active surveillance. Evidence available to support W&W approach comes from non-randomised controlled trials (RCTs) with no current consensus on patients' selection criteria, lack of viable predictors of both cCR and pCR and lack of universal definitions of cCR and pCR. Also, there is no agreed protocol for disease surveillance. Even though there has been increasing reports on the outcomes of W&W in rectal cancer, the current evidence cannot support its routine use in clinical practice. This approach should be used in clinical trials settings or after thorough counselling with the patient on the outcomes of various treatment options.

Criteria for pathological complete response (pCR) and its impact on relapse rates in breast cancer patients undergoing neo-adjuvant chemotherapy

Introduction: Pathological complete response (pCR) is used as an endpoint in various neoadjuvant trials for breast carcinoma. To date, there is no universally accepted definition of pCR, which has made reporting and interpretation of data challenging. Our objective was to establish an association between different types of pCR and event-free survival (EFS) in breast cancer patients undergoing neo-adjuvant chemotherapy (NACT).

Abstract OT1-03-01: Chemotherapy-free trastuzumab and pertuzumab in HER2 [+] breast cancer: FDG-PET response-adapted strategy. The PHERGain study

Abstract BACKGROUND: Several studies have confirmed that a significant subset of patients (pts) with early stage HER2[+]breast cancer (BC) achieve pathological complete response (pCR) with a dual HER2 neoadjuvant blockade without chemotherapy (chemo). Early metabolic evaluation using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) might help to recognize those pts with a higher likelihood of obtaining a pCR and an excellent outcome with a chemo-free strategy. TRIAL DESIGN: This is a randomized, multicenter, non-comparative phase II trial. Pts age ≥ 18 years with centrally-confirmed, treatment-naïve, HER2 [+] operable BC will be randomized, in a 1:4 ratio, and stratified by HR status, to receive docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) (cohort A), or trastuzumab and pertuzumab (HP) ± endocrine therapy (ET) according to HR status (cohort B). Centrally-reviewed 18F-FDG PET/CT scans will be performed prior to randomization and after 2 cycles of therapy. Pts allocated into cohort A will continue with the same therapy for a total of 6 cycles regardless of 18F-FDG PET/CT results. Pts enrolled into cohort B showing at least a 40% reduction of the SUVmax on 18F-FDG PET/CT respect to baseline (PET responders) will continue with the same therapy for a total of 8 cycles. PET non-responders pts will receive 6 cycles of TCHP. After surgery, cohort B/PET responders pts who do not achieve a pCR will receive 6 cycles of TCHP. Moreover, all pts from cohorts A/B must complete 18 cycles of HP, along with adjuvant ET and radiotherapy (RT) according to HR status and institutional practices, respectively. Pts with subclinic metastases will be assigned to cohort C to receive 6 cycles of TCHP. Surgery and RT will be evaluated on a case-by-case basis on cohort C, and all pts will continue with HP for at least 12 additional cycles ± ET according to HR status. The first co-primary endpoint is to evaluate the rate of pCR defined as the absence of invasive disease in the breast and axilla (ypT0/isN0) achieved with HP ± ET in PET responders pts (cohort B/PET responders).The second co-primary endpoint is to evaluate 3-year (3-y) invasive disease-free survival (iDFS) rate defined as time from the first date of no disease to invasive recurrence, new invasive disease, or death by any cause in cohort B. Total accrual will be 400 pts. Considering a 10% and 25% of drop-out rates at the time of first and second co-primary analysis, the study will be positive if ≥41 pts achieved a pCR in cohort B/PET responders; or if we observe ≤14 events of 3-y iDFS in cohort B. Decisions will be based on one-sided, exact binomial test. With a 2.5% type I error rate (H0: pCR ≤20% and 3-y iDFS ≤89%) and 80% power (HA: pCR ≥30% and 3-y iDFS ≥95%). The secondary objectives are to evaluate other definitions of pCR, rates of breast-conserving surgery, tumor response by magnetic resonance imaging, optimal 18F-FDG PET cut-off for pCR and other 18F-FDG PET quantification parameters for pCR prediction, DFS, distant-DFS, overall survival, progression-free survival, and health-related quality of life. Translational sub-studies will analyze biomarkers that may be predictive of response to dual HER2 blockade with HP. Citation Format: Llombart-Cussac A, Curigliano G, Gebhart G, Gligorov J, Khaldoun K, Marmé F, Prat A, Schmid P, Cortes J, Perez J. Chemotherapy-free trastuzumab and pertuzumab in HER2 [+] breast cancer: FDG-PET response-adapted strategy. The PHERGain study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-03-01.

Internal Mammary Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer.

PurposeThe definition of nodal pathologic complete response (pCR) after a neoadjuvant chemotherapy (NAC) just included the evaluation of axillary lymph node (ALN) without internal mammary lymph node. This study aimed to evaluate the feasibility of internal mammary-sentinel lymph node biopsy (IM-SLNB) in patients with breast cancer who underwent NAC.MethodsFrom November 2011 to 2017, 179 patients with primary breast cancer who underwent operation after NAC were included in this study. All patients received radiotracer injection with modified injection technology. IM-SLNB would be performed on patients with internal mammary sentinel lymph node (IMSLN) visualization.ResultsAmong the 158 patients with cN+ disease, the rate of nodal pCR was 36.1% (57/158). Among the 179 patients, the visualization rate of IMSLN was 31.8% (57/179) and was 12.3% (7/57) and 87.7% (50/57) among those with cN0 and cN+ disease, respectively. Furthermore, the detection rate of IMSLN was 31.3% (56/179). The success rate of IM-SLNB was 98.2% (56/57). The IMSLN metastasis rate was 7.1% (4/56), and all of them were accompanied by ALN metastasis. The number of positive ALNs in patients with IMSLN metastasis was 3, 6, 8, and 9. The pathology nodal stage had been changed from pN1/pN2 to pN3b. The pathology stage had been changed from IIA/IIIA to IIIC.ConclusionPatients with visualization of IMSLN should perform IM-SLNB after NAC, especially for patients with cN+ disease, in order to complete lymph nodal staging. IM-SLNB could further improve the definition of nodal pCR and guide the internal mammary node irradiation.

Imaging performance in guiding response to neoadjuvant therapy according to breast cancer subtypes: A systematic literature review.

Monitoring therapeutic response to neoadjuvant chemotherapy(NAC) is likely to improve NAC effectiveness in breast cancer(BC). Imaging performance seems to vary per tumour subtype(by ER and HER2 status), therefore we performed a systematic review on subtype specific imaging performance in monitoring NAC in BC. Studies examining imaging performance in predicting pathologic complete response(pCR) during NAC in BC subtypes were selected. Per study, negative- and positive predictive value, sensitivity(se) and specificity(sp), AUC and accuracy were derived. Fifteen/106 articles were included. Inter-study variability was revealed in: monitoring interval, response and pCR definitions. In ER-positive/HER2-negative BC, 181F FDG-PET/CT showed se/sp of 38%-89%/74%-100%, MRI showed se/sp of 35%-37%/87%-89%. In triple negative BC, 181F FDG-PET/CT showed se/sp of 0%-79%/95%-100%. 181F FDG-PET/CT showed in ER-positive/HER2-positive BC se/sp of 59%/80% and in ER-negative/HER2-positive 27%/88%. Evidence on imaging performance in monitoring NAC according BC subtypes is lacking. Consensus should be reached in: definitions of pCR, response and monitoring interval before starting well-designed studies.

The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis.

To review the predictive values of Ki-67 before neoadjuvant chemotherapy (NAC) for breast cancer patients. PubMed and EMBASE were searched. Random-effect model meta-analysis was conducted using Revman software. High Ki-67 was associated with more pathological complete responses (pCRs) events (odds ratio: 3.10; 95% CI: 2.52-3.81; 53 studies, 10,848 patients) regardless of HR+, HER2+ and triple-negative breast cancer types, the definitions of pCR and cut-off points for Ki-67. Ki-67 could predict pCR in those who received anthracyclines plus taxanes, and anthracyclines only, and those from Asia and Europe. High Ki-67 before NAC was a predictor for pCR in neoadjuvant setting for breast cancer patients.