Evaluation Of Pathological Response Research Articles

The role of MRI and 18F-FDG PET/CT with respect to evaluation of pathological response in the rectal cancer patients after neoadjuvant chemoradiotherapy.

We aimed to evaluate the role of magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in determining the correct stage and predicting the pathological response. Seventy one patients with pathologic proven rectal adenocarcinoma, clinical stage IIA-IVA, and neoadjuvant chemoradiotherapy (CRT) were evaluated retrospectively. Radiotherapy was delivered 45-50 Gy in 25 fractions with concomitant oral capecitabine. Pelvic MRI, colonoscopy, and 18F-FDG PET-CT were performed before the neoadjuvant treatment (NAT). After NAT, MRI and PET-CT were performed for re-evaluation. The median follow-up time was 25 months (range: 3-57 months). Of the 71 patients who underwent NAT, 57 patients underwent surgery. Downstaging was recorded in 48 (84.2%) of 57 patients who underwent surgery. There was no statistically significant difference between both MRI and PET-CT with pathology results in terms of response evaluation. As a result of the comparison of MRI and PET-CT with pathological results; sensitivity and specificity were 91.6% (44/48) and 22.2% (2/9) for MRI, and 100% (47/47) and 12.5% (1/8) for PET-CT, respectively. PET-CT and MRI are effective in predicting response to NAT and predictive for the pathological response. A more accurate response can be judged when both PET-CT and MRI are executed together in restaging after NAT.

The Importance of the Pathological Perspective in the Management of the Invasive Lobular Carcinoma.

Background Invasive lobular carcinomas (ILC) account for 10–15% of all breast cancers and are the second most common histological form of breast cancer. They usually show a discohesive pattern of single cell infiltration, tend to be multifocal, and the tumor may not be accompanied by a stromal reaction. Because of these histological features, which are not common in other breast tumors, radiological detection of the tumor may be difficult, and its pathological evaluation in terms of size and spread is often problematic. The SSO-ASTRO guideline defines the negative surgical margin in breast-conserving surgeries as the absence of tumor detection on the ink. However, surgical margin assessment in invasive lobular carcinomas has not been much discussed from the pathological perspective. Methods The study included 79 cases diagnosed with invasive lobular carcinoma by a Tru-cut biopsy where operated in our center between 2014 and 2021. Clinicopathological characteristics of the cases, results of an intraoperative frozen evaluation in cases that underwent conservative surgery, the necessity of re-excision and complementary mastectomy, and consistency in radiological and pathological response evaluation in cases receiving neoadjuvant treatment were questioned. Results The tumor was multifocal in 37 (46.8%) cases and single tumor focus in 42 (53.2%) cases. When the entire patient population was evaluated, regardless of focality, mastectomy was performed in 27 patients (34.2%) and breast-conserving surgery (BCS) was performed in 52 patients (65.8%). Of the 52 patients who underwent BCS, 26 (50%) required an additional surgical procedure (cavity revision or completion mastectomy). There is a statistical relationship between tumor size and additional surgical intervention (p < 0.05). BCS was performed in 7 of 12 patients who were operated on after neoadjuvant treatment, but all of them were reoperated with the same or a second session and turned to mastectomy. Neoadjuvant treatment and the need for reoperation were statistically significant (p < 0.05). Additional surgical procedures were performed in 20 (44.4%) of 45 patients in BCS cases who did not receive neoadjuvant therapy. Conclusions Diagnostic difficulties in the intraoperative frozen evaluation of invasive lobular carcinoma are due to the different histopathological patterns of the ILC. In our study, it was determined that large tumor size and neoadjuvant therapy increased the need for additional surgical procedures. It is thought that the pathological perspective is the determining factor in order to minimize the negative effects such as unsuccessful cosmesis, an additional surgical burden on the patient, and cost increase that may occur with additional surgical procedures; for this reason, new approaches should be discussed in the treatment planning of invasive lobular carcinoma cases.

EP05.02-019 Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Surgical Outcomes in a Regionalized Pulmonary Oncology Network

Neoadjuvant therapy (NAT) allows pre-operative tumor downstaging and evaluation of pathological response. Clinical trials have demonstrated benefit of using NAT in the context of locally advanced non-small cell cancer (NSCLC). However, NAT is not commonly employed around the world and data are lacking as to how to establish a NAT program for locally advanced resectable NSCLC. The aim of this study is to evaluate the evolution in care patterns for patients with resectable locally advanced NSCLC within a regionalized pulmonary oncology academic network and to assess the impact of transition towards a large-scale NAT program.

Pathological Response and Immune Biomarker Assessment in Non-Small-Cell Lung Carcinoma Receiving Neoadjuvant Immune Checkpoint Inhibitors.

Simple SummaryRecently, the U.S. Food and Drug Administration (FDA) approved neoadjuvant immunotherapy plus chemotherapy for the treatment of resectable non-small-cell lung carcinoma (NSCLC) due to the clinical benefits reported in several clinical trials. In these settings, the pathological assessment of the tumor bed to quantify a pathological response has been used as a surrogate method of clinical benefit to neoadjuvant therapy. In addition, several clinical trials are including the assessment of tissue-, blood-, or host-based biomarkers to predict therapy response and to monitor the response to neoadjuvant treatment. In this manuscript, we provide an overview of current recommendations for the evaluation of pathological response and describe potential biomarkers used in clinical trials of neoadjuvant immunotherapy in resectable NSCLC.Lung cancer is the leading cause of cancer incidence and mortality worldwide. Adjuvant and neoadjuvant chemotherapy have been used in the perioperative setting of non-small-cell carcinoma (NSCLC); however, the five-year survival rate only improves by about 5%. Neoadjuvant treatment with immune checkpoint inhibitors (ICIs) has become significant due to improved survival in advanced NSCLC patients treated with immunotherapy agents. The assessment of pathology response has been proposed as a surrogate indicator of the benefits of neaodjuvant therapy. An outline of recommendations has been published by the International Association for the Study of Lung Cancer (IASLC) for the evaluation of pathologic response (PR). However, recent studies indicate that evaluations of immune-related changes are distinct in surgical resected samples from patients treated with immunotherapy. Several clinical trials of neoadjuvant immunotherapy in resectable NSCLC have included the study of biomarkers that can predict the response of therapy and monitor the response to treatment. In this review, we provide relevant information on the current recommendations of the assessment of pathological responses in surgical resected NSCLC tumors treated with neoadjuvant immunotherapy, and we describe current and potential biomarkers to predict the benefits of neoadjuvant immunotherapy in patients with resectable NSCLC.

Evaluation of pathological complete response after neoadjuvant systemic treatment of invasive breast cancer using diffusion-weighted imaging compared with dynamic contrast-enhanced based kinetic analysis

PurposeThis study compared the performance of diffusion-weighted imaging (DWI) to dynamic contrast-enhanced (DCE)-MRI for diagnosing pathological complete response (pCR) before surgery. MethodOverall, 133 lesions from 133 patients who underwent pre-surgical MRI evaluation after neoadjuvant systemic treatment were included. Two readers blinded to the pathological diagnosis evaluated the images. MR images were obtained using a routine protocol sequence that included DWI and DCE-MRI. DWI of the target lesion was scored using a three-point scale. Kinetic patterns of lesions on DCE-MRI were scored using a four-point scale. The capacities of DWI and kinetic parameters for discriminating pCR and non-pCR were assessed via receiver operating characteristic (ROC) analysis. ResultsFor DWI scores, ROC analysis showed areas under the ROC curve (AUCs) of 0.84 (95% confidence interval: 0.77–0.90) and 0.85 (0.77–0.90) for readers 1 and 2, respectively; corresponding AUCs of kinetic scores were 0.89 (0.82–0.94) and 0.88 (0.81–0.93). Among the triple-negative subtype, the AUCs of DWI scores were 0.84 (0.70–0.93) and 0.88 (0.75–0.96) for readers 1 and 2, respectively; corresponding AUCs of kinetic scores were 0.94 (0.83–0.99) and 0.93 (0.82–0.99). Among the luminal subtype, the AUCs of DWI scores were 0.85 (0.71–0.94) and 0.82 (0.68–0.92) for readers 1 and 2, respectively; corresponding AUCs of kinetic scores were 0.82 (0.68–0.92) and 0.72 (0.56–0.85). ConclusionsOur DWI-based visual score and kinetic score showed similar diagnostic performances. Both DWI and kinetic scores tended to perform better in predicting pCR for the triple-negative subtype.

Magnetic Resonance Imaging Evaluation of Pathological Response in Breast Cancer After Neoadjuvant Chemotherapy

Magnetic Resonance Imaging Evaluation of Pathological Response in Breast Cancer After Neoadjuvant Chemotherapy

Abstract OT2-19-01: Presurgical treatment with ribociclib and letrozole in patients with locally advanced breast cancer: The NEOLETRIB study

Abstract Background: The introduction of CDK4/6 inhibitors has been one of the most pivotal breakthroughs in breast cancer therapy in recent decades. A growing body of evidence now suggests that novel targeting inhibitors of CDK4/6, as well as MAPK and PI3K inhibitors, might have anti-tumor effects beyond tumour cell cytostasis, including immunomodulation. Specifically, studies have demonstrated that CDK4/6 inhibitors can have immunogenic effects, through the induction of a senescent-like phenotype in tumor cells, changes in tumor cell metabolism, and direction modulation of T cell function. Trial design: NEOLETRIB is a multicenter, single-arm, open-label, neoadjuvant, phase II trial. Eligibility criteria: Patients suffering from locally advanced breast cancer defined as either large T2 (&amp;gt; 3 cm), or T3/T4, and/or N2-3 are suitable for inclusion. Both, luminal-A and luminal-B tumors are allowed. HER-2 positive and triple-negative patients are excluded from this trial, as are patients with patients with evidence of distant metastasis. Treatment: All patients receive neoadjuvant therapy for at least 6 months with ribociclib (600 mg daily, 21 days on/7 days off) and letrozole (2.5 mg daily). Premenopausal women will also receive goserelin (3.6 mg s.c. every 28 days) according to clinical practice. Specific aims: The primary objective is to evaluate the intra-tumor immunological effects in individual patients treated with letrozole and ribociclib in the neoadjuvant setting. Secondary objectives include evaluation of clinical and pathological response to the treatment combination, identification of early and late molecular mechanisms of treatment adaptation and resistance, and investigation of the effects of the treatment on the gut microbiota and vice versa. As an exploratory objective, we aim to study the relationship between cancer treatment effects, the immune competent cells in the blood and the gut microbiota. Long-term follow-up will continue after the primary analysis for up to 10 years or until death, withdrawal of consent, loss to follow-up, or trial closure. To allow for the planned laboratory sub-studies, tumor tissue biopsies, blood and stool samples will be collected at baseline, day 21 and at time of surgery, with additional blood and stool samples collected at day 90. The samples will be analyzed to evaluate and measure numerous parameters including levels of cytokines and metabolites, cell free DNA-fragments, and intra-tumor gene expression/regulation using state of the art laboratory methods together with international collaborators. Advanced MRI-techniques are used at baseline and following 3 and 6 months on treatment for clinical efficacy measurements in the breast. Statistical methods: Due to the nature of this single-arm study with longitudinal sampling from individual patients, the statistics will be descriptive in nature, focusing on intra-patient comparisons over time. The inclusion goal of 100 patients is based on the response rate of neoadjuvant trials with ribociclib to allow for a minimum of 30 patients in the responder &amp; non-responder arms, which is sufficient for hypothesis generating results. Present accrual and target accrual: Following 8 weeks after initiation of this trial, the first 10 patients have been enrolled. The target accrual is 100 patients with complete study procedures. Citation Format: Xavier Tekpli, Shom Goel, Barbro Holm, Lars-Egil Fallang, Laurens Cornelus Reitsma, Stephanie Beate Geisler, Hilde Presterud Ødegård, Cathrine Bergquist Fosskaug, Ida Caroline Lindem, Manouchehr Seyedzadeh, Jonn Terje Geitung, Joana Reis, Kjell Inge Gjesdal, Unn-Cathrin Buvarp, Marie Loeng, Kristine Kleivi Sahlberg, Alina Carmen Porojnicu, Helle Kristine Skjerven, Andliena Tahiri, Shakila Jabeen, Torben Lüders, Vahid Bemanian, Jørgen Jahnsen, Marianne Lyngra, Antoni Hurtado, Jason Carroll, Shiuan Chen, Vessela Kristensen, Jürgen Geisler. Presurgical treatment with ribociclib and letrozole in patients with locally advanced breast cancer: The NEOLETRIB study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-19-01.

Evaluation of pathological response in patient with resectable gastric cancer and perioperative FLOT versus XELOX chemotherapy (PECORINO trial)

Background: Gastric cancer remains one of the leading causes of cancer-related mortality in Ukraine. The guidelines on diagnosis and treatment of gastric cancer are still undefined within our country thus having poor outcomes. The most frequently used regimen in Ukraine is XELOX, but the latest data suggest to use FLOT regimen. The first one is more convenient from the patient perspective, the second one supposedly has more aggresive toxicity profile with better pathological response. The aim of the study is to define optimal treatment modality for gastric cancer.

Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.

Evaluation of Clinical and Pathological Response in Breast Cancer Following Neoadjuvant Chemotherapy- A Single Institution Experience

Evaluation of Clinical and Pathological Response in Breast Cancer Following Neoadjuvant Chemotherapy- A Single Institution Experience

Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis

ObjectiveTo evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and...

Prediction of Pathologic Complete Response in Breast Cancer Patients Comparing Magnetic Resonance Imaging with Ultrasound in Neoadjuvant Setting.

Some subgroups of breast cancer patients receiving neoadjuvant chemotherapy (NACT) show high rates of pathologic complete response (pCR) in the breast, proposing the possibility of omitting surgery. Prediction of pCR is dependent on accurate imaging methods. This study investigated whether magnetic resonance imaging (MRI) is better than ultrasound (US) in predicting pCR in breast cancer patients receiving NACT. This institutional, retrospective study enrolled breast cancer patients receiving NACT who were examined by either MRI or combined US and mammography before surgery from 2016 to 2019. Imaging findings were compared with pathologic response evaluation of the tumor. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for prediction of pCR were calculated and compared between MRI and US. Among 307 patients, 151 were examined by MRI and 156 by US. In the MRI group, 37 patients (24.5 %) had a pCR compared with 51 patients (32.7 %) in the US group. Radiologic complete response (rCR) was found in 35 patients (23.2 %) in the MRI group and 26 patients (16.7 %) in the US group. In the MRI and US groups, estimates were calculated respectively for sensitivity (87.7 % vs 91.4 %), specificity (56.8 % vs 33.3 %), PPV (86.2 % vs 73.8 %), NPV (60.0 % vs 65.4 %), and accuracy (80.1 % vs 72.4 %). In predicting pCR, MRI was more specific than US, but not sufficiently specific enough to be a valid predictor of pCR for omission of surgery. As an imaging method, MRI should be preferred when future studies investigating prediction of pCR in NACT patients are planned.

Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study.

505 Background: Talazoparib (TALA) is a poly(ADP-ribose) polymerase inhibitor approved as monotherapy for treating adult patients (pts) with g BRCA1/2-mutated HER2-negative locally advanced or metastatic BC. Methods: This phase 2, non-randomized, single-arm, open-label study (NCT03499353) evaluated the efficacy and safety of TALA in the neoadjuvant setting for pts with early g BRCA1/2-mutated HER2− BC. Primary endpoint was evaluation of pathologic complete response (pCR) as assessed by Independent Central Review (ICR) after completing 24 weeks of neoadjuvant TALA monotherapy 1 mg QD (0.75 mg for moderate renal impairment) followed by surgery. Secondary endpoints included pCR by investigator (INV) and residual cancer burden (RCB) by ICR (RCB: 0 [pCR], I [minimal], II [moderate], III [extensive]). The evaluable population included pts who received at least 80% of the TALA dose prescribed at treatment start and underwent breast surgery and pCR assessment, plus those who progressed before pCR could be assessed. The intent-to-treat (ITT) population included all pts who received at least 1 dose of TALA. Results: Of 61 pts treated with TALA (ITT and safety populations), 48 comprised the evaluable population. All pts had triple-negative BC. 60 pts had adenocarcinoma and 1 had squamous cell histology, with the following staging: I=20, II=27, III=14. Mean age was 44.6 years, mean duration of 4.5 wks since disease onset, mean duration of treatment of 23.3 wks, and mean overall relative dose intensity of 84.5% (ITT population). pCR (assessed by ICR and INV) and RCB (by ICR) for the evaluable and ITT populations are shown in the table below. Ten (16.4%) patients discontinued treatment due to progressive disease. One pt had a disruption of treatment as a result of COVID-19 restrictions, 2 pts for other reasons: to undergo surgery early and consent withdrawal; 9 patients received &lt;80% dose. Treatment-emergent adverse events (AEs) were reported in 98.4% of pts (27.9% grade [G] 1, 23.0% G2, 45.9% G3, 1.6% G4); the most common were fatigue (78.7%; G1 54.1%; G2 21.3%; G3 3.3%), nausea (68.9%; G1 54.1%; G2 13.1%; G3 1.6%), and alopecia (57.4%; G1 54.1%; G2 3.3%). Three (4.9%) pts discontinued treatment due to AEs (G3 anemia [n=2] and G3 vertigo [n=1]) and continued on study. Conclusions: TALA monotherapy in the neoadjuvant setting was active and showed pCR rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens and was generally well tolerated. Clinical trial information: NCT03499353. [Table: see text]

Evaluation of Pathologic Response in Lymph Nodes of Patients With Lung Cancer Receiving Neoadjuvant Chemotherapy

IntroductionMajor pathologic response (MPR), defined as residual viable tumor of less than or equal to 10%, currently serves as a surrogate end point for survival for patients with resectable NSCLC after neoadjuvant chemotherapy. However, the significance of pathologic response in lymph nodes harboring metastatic tumors in such patients remains uncertain. Therefore, we studied the effect of neoadjuvant chemotherapy on resected positive lymph nodes and determined if the degree of pathologic response in the lymph nodes alone (LN-MPR) or in combination with that of the primary tumor (PT-MPR) was able to predict the outcome. MethodsA total of 75 patients with NSCLC who underwent neoadjuvant chemotherapy and completed surgical resection were included in this study. Tissue specimens were retrospectively evaluated by two pathologists blinded to the patients’ treatments and outcomes. Specimens were reviewed for the degree of pathologic response in the primary tumor and in any involved lymph nodes. The prognostic performance of LN-MPR alone or in combination with PT-MPR with respect to overall survival (OS) was evaluated using the Kaplan-Meier method and Cox regression model. ResultsLN-MPR was significantly predictive of long-term OS after neoadjuvant chemotherapy. A combination of PT-MPR with LN-MPR was significantly associated with outcome and allowed stratification of patients into three prognostic groups (p = 0.001). ConclusionsLN-MPR in isolation is a reliable predictor of OS in patients with NSCLC receiving neoadjuvant chemotherapy. A combination of LN-MPR with PT-MPR seems to correlate well with the outcome and can be used to predict prognosis in this patient population.

Evaluation of Post-Neoadjuvant Chemotherapy Pathologic Complete Response and Residual Tumor Size of Breast Cancer: Analysis on Accuracy of MRI and Affecting Factors

목적신보강화학요법을 시행한 유방암 환자에서 병리학적 관해와 잔류 암의 크기를 평가하는 데 있어 유방자기공명영상의 정확도를 분석하고 이에 영향을 미치는 인자들이 무엇인지 알아본다.대상과 방법2010년부터 2017년까지 본원에서 신보강화학요법 후 수술을 시행한 88명의 유방암 환자를 대상으로 하였다. 병리학적 관해는 수술 병리 결과에서 침윤성 유방암이 발견되지 않는 것으로 정의하였고 자기공명영상과 병리 조직의 잔류 암 크기 차이는 최대 직경으로 비교하였다. 병리학적 관해 및 자기공명영상과 병리 조직에서의 잔류 암 크기 차이에 영향을 미치는 인자를 알아보기 위해 통계분석을 시행하였다.결과전체 환자의 10%가 병리학적 관해에 도달하였다. 자기공명영상으로 관해를 예측할 때의 정확도와 곡선하부면적은 각각 90.91%, 0.8017이었다. 신보강화학요법 시행 후 유방자기공명영상과 병리 조직에서 측정한 잔류 암의 크기는 매우 강한 연관성을 보였고(r = 0.9, p < 0.001), 특히 영상에서 단일 종괴로 보였던 병변에서(p = 0.047) 그러하였다. 자기공명영상과 병리 조직 간의 잔류 암 크기는 내강형(p = 0.023), 그리고 자기공명영상에서 다초점 종괴 및 비종괴성 조영증강을 보인(p = 0.047) 환자군에서 유의미하게 큰 차이를 보였다.결론자기공명영상은 유방암의 병리학적 완전 관해와 잔류 암 크기의 평가에 있어서 정확도가 높은 검사이다. 유방암 아형과 병변의 영상의학적 소견이 자기공명영상의 정확도에 영향을 미친다.

5MO Evaluation of pathological complete response (pCR) after neoadjuvant chemo-radiation therapy for primary breast cancer (JCOG0306A1)

5MO Evaluation of pathological complete response (pCR) after neoadjuvant chemo-radiation therapy for primary breast cancer (JCOG0306A1)

203P Comparison of two pathologic response evaluation classification after neoadjuvant chemotherapy in patients with breast cancer

203P Comparison of two pathologic response evaluation classification after neoadjuvant chemotherapy in patients with breast cancer

Correlation of RECIST, Computed Tomography Morphological Response, and Pathological Regression in Hepatic Metastasis Secondary to Colorectal Cancer: The AVAMET Study.

Background: The prospective phase IV AVAMET study was undertaken to correlate response evaluation criteria in solid tumors (RECIST)-defined response rates with computed tomography-based morphological criteria (CTMC) and pathological response after liver resection of colorectal cancer metastases. Methods: Eligible patients were aged ≥18 years, with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and histologically-confirmed colon or rectal adenocarcinoma with measurable liver metastases. Preoperative treatment was bevacizumab (7.5 mg on day 1) + XELOX (oxaliplatin 130 mg/m2, capecitabine 1000 mg/m2 bid on days 1–14 q3w). After three cycles, response was evaluated by a multidisciplinary team. Patients who were progression-free and metastasectomy candidates received one cycle of XELOX before undergoing surgery 3–5 weeks later, followed by four cycles of bevacizumab + XELOX. Results: A total of 83 patients entered the study; 68 were eligible for RECIST, 67 for CTMC, and 51 for pathological response evaluation. Of these patients, 49% had a complete or partial RECIST response, 91% had an optimal or incomplete CTMC response, and 81% had a complete or major pathological response. CTMC response predicted 37 of 41 pathological responses versus 23 of 41 responses predicted using RECIST (p = 0.008). Kappa coefficients indicated a lack of correlation between the results of RECIST and morphological responses and between morphological and pathological response rates. Conclusion: CTMC may represent a better marker of pathological response to bevacizumab + XELOX than RECIST in patients with potentially-resectable CRC liver metastases.

Evaluation of Pathologic Complete Response as a Surrogate for Long-Term Survival Outcomes in Triple-Negative Breast Cancer

Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41-0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01-0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.

Evaluation of Pathologic Response on Overall Survival After Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma.

Single-institution studies have shown improved outcomes among patients with a pathologic complete response (pCR) following neoadjuvant therapy. We sought to evaluate the impact of pCR and near-complete response (nCR) on overall survival (OS) using a large national database. The National Cancer Database was queried for patients given a diagnosis of pancreatic cancer from 2004 to 2014. A pCR was defined as no tumor identified in the pancreas after surgical resection. An nCR was defined as a primary tumor less than 1 cm without lymph node metastases. The primary outcome was OS. A total of 5364 patients underwent neoadjuvant chemotherapy and/or radiation followed by pancreatectomy. Forty-one patients (0.8%) had a pCR, 54 (1%) had an nCR, and the remaining 5266 (98.2%) had an otherwise incomplete response. Patients with pCR had a median OS of 43 months compared with 24 months for nCR and 23 months for incomplete response (P < 0.0001). Only pCR was associated with improved OS on adjusted Cox regression. For patients given a diagnosis of pancreatic cancer who underwent neoadjuvant treatment and surgical resection, achieving a pCR was associated with improved OS compared with those with residual tumor. An association between nCR and improved survival was not observed.