Courses Of Neoadjuvant Chemotherapy Research Articles

EXPRESSION OF ALU REPEAT IN BLOOD PLASMA OF PATIENTS WITH BREAST CANCER DURING NEOADJUVANT CHEMOTHERAPY: AN EXPLORATORY STUDY.

Locally advanced breast cancer(LABC)rates are unusually high in developing countries. There is a need for the identification of predictive biomarkers for the selection of patients who could benefit from neoadjuvant chemotherapy (NAC). As the expression of ALU repeat is increased in cancer and has not been assessed in liquid biopsy of cancer patients, our goal was to assess ALU expression in the blood plasma of LABC patients during NAC. Plasma samples drawn at baseline and at the end of the fourth cycle of chemotherapy were used to determine the plasma levels of ALU-RNA by quantitative real-time PCR. ALU expression from baseline to the fourth cycle of NAC increased from a median relative level of 1870 to 3370 in the whole group (p = 0.03). The increase in ALU-RNA levels in the course of NAC was more pronounced in premenopausal women and in patients with hormone-positive tumors. In patients with complete response to NAC, baseline ALU expression was higher than that in those with partial response. This exploratory study provides evidence that plasma ALU-RNA levels are modulated by the menopausal status and hormone receptor status of breast cancer patients and pre-therapeutic ALU-RNA levels might be useful in predicting the response to chemotherapy in a neoadjuvant setting.

MALE BREAST CANCER TREATMENT: A CLINICAL CASE*

Relevance: Male breast cancer (BC) has always been behind female BC in detection, treatment, and surveillance. Lower BC frequency in men limits the usefulness of screening. However, BC incidence in men is growing.
 This paper demonstrate the results of surgical treatment and typical changes in clinical and morphological manifestations of male breast cancer under chemotherapy and surgery.
 Methods: The article describes a clinical case of a male patient diagnosed with “Cancer of the right breast St III (T4NxM0), edematous-infiltrative form with an intraductal component, upper outer localization. Immunohistochemically luminal subtype B without Her2neu expression”; the condition – after six neoadjuvant chemotherapy courses.
 Results: Ultrasonography of the mammary glands conducted after six preoperative courses of chemotherapy showed a hypoechoic formation, centralized, with fuzzy, uneven contours, 52.5×48.2×46.1 mm in size, V=60.98 cm3. Compared to March 2022 (the presence of a formation in the right breast craniolateral quadrant, with precise uneven contours, 9.0 cm in size, with infiltrating growth), the tumor formation decreased to US BI-RADS R6, L2. The multidisciplinary council prescribed surgery to the extent of radical mastectomy by Madden on the right and simple mastectomy on the left. The surgery was performed in August 2022. According to a postoperative histological conclusion, the therapeutic pathomorphism was index RCB-2.233, class RCB-II.
 Conclusion: This article shares the results of systemic and surgical treatment of a man with breast cancer. Considering the clinical picture and anamnesis, literature data, and the clinical protocol, the multidisciplinary group recommended radiation therapy with adjuvant endocrine therapy with tamoxifen for an initial period of five years.
 * clinical case, male breast cancer (BC), luminal subtype B without Her2neu expression, mastectomy, therapeutic pathomorphism, radiation therapy, endocrine therapy.

MALE BREAST CANCER TREATMENT: A CLINICAL CASE*

Relevance: Male breast cancer (BC) has always been behind female BC in detection, treatment, and surveillance. Lower BC frequency in men
 limits the usefulness of screening. However, BC incidence in men is growing.
 This paper demonstrates the results of surgical treatment and typical changes in clinical and morphological manifestations of male breast
 cancer under chemotherapy and surgery.
 Methods: The article describes a clinical case of a male patient diagnosed with “Cancer in the right breast St III (T4NxM0), edematousinfiltrative form with an intraductal component, upper outer localization. Immunohistochemically luminal subtype B without Her2neu expression”;
 the condition – after six neoadjuvant chemotherapy courses.
 Results: Ultrasonography of the mammary glands conducted after six preoperative courses of chemotherapy showed a hypoechoic formation,
 centralized, with fuzzy, uneven contours, 52.5×48.2×46.1 mm in size, V=60.98 cm3
 . Compared to March 2022 (the presence of a formation in
 the right breast craniolateral quadrant, with precise uneven contours, 9.0 cm in size, with infiltrating growth), the tumor formation decreased to
 US BI-RADS R6, L2. The multidisciplinary council prescribed surgery to the extent of radical mastectomy by Madden on the right and simple
 mastectomy on the left. The surgery was performed in August 2022. According to a postoperative histological conclusion, the therapeutic pathomorphism was index RCB-2.233, class RCB-II.
 Conclusion: This article shares the results of systemic and surgical treatment of a man with breast cancer. Considering the clinical picture and
 anamnesis, literature data, and the clinical protocol, the multidisciplinary group recommended radiation therapy with adjuvant endocrine therapy
 with tamoxifen for an initial period of five years.

MALE BREAST CANCER TREATMENT: A CLINICAL CASE*

Relevance: Male breast cancer (BC) has always been behind female BC in detection, treatment, and surveillance. Lower BC frequency in men
 limits the usefulness of screening. However, BC incidence in men is growing.
 This paper demonstrates the results of surgical treatment and typical changes in clinical and morphological manifestations of male breast
 cancer under chemotherapy and surgery.
 Methods: The article describes a clinical case of a male patient diagnosed with “Cancer in the right breast St III (T4NxM0), edematousinfiltrative form with an intraductal component, upper outer localization. Immunohistochemically luminal subtype B without Her2neu expression”;
 the condition – after six neoadjuvant chemotherapy courses.
 Results: Ultrasonography of the mammary glands conducted after six preoperative courses of chemotherapy showed a hypoechoic formation,
 centralized, with fuzzy, uneven contours, 52.5×48.2×46.1 mm in size, V=60.98 cm3
 . Compared to March 2022 (the presence of a formation in
 the right breast craniolateral quadrant, with precise uneven contours, 9.0 cm in size, with infiltrating growth), the tumor formation decreased to
 US BI-RADS R6, L2. The multidisciplinary council prescribed surgery to the extent of radical mastectomy by Madden on the right and simple
 mastectomy on the left. The surgery was performed in August 2022. According to a postoperative histological conclusion, the therapeutic pathomorphism was index RCB-2.233, class RCB-II.
 Conclusion: This article shares the results of systemic and surgical treatment of a man with breast cancer. Considering the clinical picture and
 anamnesis, literature data, and the clinical protocol, the multidisciplinary group recommended radiation therapy with adjuvant endocrine therapy
 with tamoxifen for an initial period of five years.

Efficacy of preoperative therapy in patients with high and low risk of distant metastasis in non-small cell lung cancer

Background. To select the optimal treatment for non-small cell lung cancer (NSCLC), it is important to predict the risk of distant metastasis and the effectiveness of therapy. The effect of neoadjuvant chemotherapy (NAC) on distant metastasis remains poorly understood. In this study we evaluated the feasibility of predicting the risk of distant metastasis and effectiveness of various treatment options for pre- and intraoperative therapy in NSCLC patients with high and low risk of distant metastasis, divided based on the assessment of morphological changes in the epithelium of small bronchi located near the primary tumor.Material and Methods. The study included 171 patients with NSCLC (T1-4N0-3M0). Various premalignant lesions: isolated basal cell hyperplasia (BCH+SM-D-), basal cell hyperplasia with squamous cell metaplasia (BCH+SM+D-) and squamous cell metaplasia with dysplasia (BCH-SM+D+) were identified in the bronchial epithelium of small bronchi taken at a distance of 3–5 cm from the tumor. Preliminary studies have shown that the detection of BCH+SM-D- or BCH-SM+D-in small bronchi are the markers of high risk of NSCLC distant metastasis, and the detection of BCH+SM+D- and BCH-SM-D- are the markers of low risk of NSCLC distant metastasis. 52.6 % of patients (90/171) received 2–3 courses of neoadjuvant chemotherapy (NAC), 41.1 % (37/90) of patients underwent intraoperative radiation therapy (IORT) at a single dose of 10–15 Gy and 47.4 % (81/171) of patients received platinum-based adjuvant chemotherapy (AC).Results. Both treatment options (NAC+IORT+ and NAC+IORT–) effectively reduced the incidence of distant metastases in the high-risk group patients during the first 2 years of follow-up compared with the high-risk group patients who did not received therapy. In the low-risk group patients, distant metastases rarely occurred, regardless of the treatment option. Adjuvant chemotherapy was found to have no influence on the frequency of distant metastases. Metastasis-free and overall survival rates were better in the low-risk group patients or in patients who received the NAC+IORT+ regimen.Conclusion. Combination of NAC and IORT resulted in the increase in metastasis-free and overall survival rates.

Multiparametric Magnetic Resonance Imaging in Determining Prognostic Factors for Cervical Cancer IB2-IIB Stages after Neoadjuvant Chemotherapy

Background : Comprehensive treatment of locally advanced cervical cancer (CC) requires the use of informative diagnostic methods to assess tumor size, extent of the tumor and other factors that determine prognosis of the disease. Purpose : Determination of diagnostic opportunities of multiparametric magnetic resonance imaging (mpMRI) in the visualization of residual tumor and assessment of the main prognostic factors in patients with stage IB2-IIB cervical cancer (FIGO) after neoadjuvant chemotherapy (NACT). Material and methods : Patients with stage IB2-IIB cervical cancer (n = 120) were prospectively enrolled in the study; they received NACT followed by surgical treatment or chemoradiotherapy (CRT). Patients underwent mpMRI before NACT and not later than 14 days after the 3rd course of NACT. To determine the diagnostic opportunities of mpMRI, MRI-data were compared with pathomorphological results. In the comparative analysis were included the following factors: residual tumor size (maximum diameter), depth of stromal invasion (mm), presence of parametrial invasion. Potential MRI-signs suggestive for lymphovascular invasion (LVI) of the parametrium were also assessed. Results : Obtained MRI-data about the size of the residual tumor and the depth of stromal invasion showed statistically significant correlation with the results of pathomorphological study (p < 0.0001) — R 2 = 0.77 and 0.69, respectively. Difference value in measuring the maximum diameter of the residual tumor was on the average 2.52±6.76 mm. MRI sensitivity in the assessment of parametrial invasion was 71.4 %, specificity — 95.1 %, accuracy — 88.9 %, PVPR — 71.4 %, PVNR — 95.1 %. Potential predictors significantly associated with parametrial LVI were identified: parametrial edema (p = 0.001) and dilatation of parametrial vessels (> 3 mm) (p = 0.015). According to these factors was developed a mathematical model, which predicts the risk of having parametrial LVI before surgery in patients after NACT. Conclusion : Multiparametric MRI is an effective technique in assessing the size of the residual tumor, depth of stromal invasion and parametrial invasion in patients with stage IB2-IIB cervical cancer after NACT. MpMRI makes it possible to assess potential signs, associated with parametrial LVI in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy and radical cystectomy in patients with bladder cancer

Background. Bladder cancer is the ninth most common malignant neoplasm worldwide. Hidden metastases at the time of diagnosis are the main reason muscle-invasive bladder cancer has poor prognosis. Even after radical cystectomy, muscleinvasive bladder cancer mostly progresses within 2 years with a recurrence rate of over 50 %. At stages II–IV of the disease, drug treatment is indicated before radical cystectomy. The main goal of neoadjuvant chemotherapy is to affect micrometastases, which may be present at the beginning of disease development. The response to ongoing chemotherapy can serve as a predictor of long-term survival.Aim. To increase effectiveness of bladder cancer treatment.Materials and methods. A total of 231 patients with bladder cancer were included in the study. The main contingent consisted of men over 60 years old with locally advanced tumors at stage Т2–Т4. Drug therapy was carried out in neoadjuvant mode before surgical treatment. Standard regimens were used: cisplatin + gemcitabine and MVAC (methotrexate, vinblastine, adriamycin, cisplatin). After four courses of neoadjuvant chemotherapy, the results were evaluated. With complete normalization of a patient’s condition, the issue of surgical treatment – radical cystectomy with one of the types of urinary diversion – was decided.Results and conclusion. The follow-up period for patients after treatment was 62 months. In patients who underwent neoadjuvant chemotherapy, the median overall survival was 44.9 months, in patients without neoadjuvant treatment – 36.8 months with improvement in recurrence-free survival from 32.5 to 39.8 months (p = 0.08). Overall survival after neoadjuvant chemotherapy improved by 8.1 months (p = 0.09).

Prognostic and Predictive Significance of mRNA Expression of ABC-transporter Genes in Patients with Non-small Cell Lung Cancer

Introduction. To date, one of the reasons for the ineffectiveness of chemotherapy in various malignant neoplasms, including lung cancer, is the formation of the multidrug resistance (MDR) phenotype in tumor cells, which is caused by the expression of ABC transporter genes.Aim. The aim of this work was to assess the expression of ABC-transporter genes during chemotherapy and to analyze the relationship with the effectiveness of chemotherapy and prognosis of the disease.Materials and methods. We used biopsy and surgical material from 91 patients with stage IIB–IIIA non-small cell lung cancer (NSCLC). The treatment regimen included: 2 courses of neoadjuvant chemotherapy (NAC), surgery and 3 courses of adjuvant chemotherapy (ACT) with platinum doublets. RNA was isolated from the samples, followed by quantitative PCR to assess the expression of genes ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2.Results and discussion. It was shown that the level of expression of the studied genes was not associated with the effect of NAC in patients with lung cancer, except for the ABCC5 gene, which showed a relationship at the level of a pronounced trend (p = 0.07). It was also shown that in the group of patients with an objective response to chemotherapy, the frequency of decreased expression of the ABCC1 (p = 0.01) and ABCC5 (p = 0.004) genes was statistically significantly higher than in the group of patients with stabilization. Further, using the Kaplan – Meier method, it was found that a decrease in expression is associated with high rates of metastatic-free survival (MFS). The highest rates of 5-year MFS (more than 85 %) are observed in patients with a decrease in the expression of the ABCB1 and ABCG2 genes, log-rank test p = 0.0007 and p = 0.002, respectively.Conclusion. Thus, it has been shown that changes in the expression of ABC transporter genes are associated with the effectiveness of chemotherapy and the prognosis of the disease. The data obtained can be used as a basis for the detection of potential drug targets.

Preliminary observational study of the implementation of hyperthermic intraperitoneal chemotherapy in ovarian cancer in the gynecological surgery department at the University Hospital of Strasbourg

ObjectiveAccording to French guidelines, hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed for Federation of Gynecology and Obstetrics stage III primary epithelial ovarian, tubal, and peritoneal cancers that are initially unresectable after 3 or 4 cycles of intravenous chemotherapy. The main objective of this preliminary study was to analyze the components necessary for the establishment of HIPEC in an expert gynecological oncological surgery center. The secondary objective was to compare HIPEC using conventional laparotomy and laparoscopic approaches. MethodsWe conducted a single-center retrospective study of patients who received HIPEC. All patients who met the criteria of the French HIPEC guidelines were included from 2019 to 2021. ResultsPrior to HIPEC, there were a mean of 3.7 courses of neoadjuvant chemotherapy with carboplatin and paclitaxel. Of the 16 patients who received HIPEC, 9 (56.2%) underwent HIPEC laparoscopically, while 7 (43.8%) underwent laparotomy. There were no differences between the rates of intra- and postoperative complications between the two groups. (p > 0.05). The duration of hospitalization was significantly shorter in patients who were operated laparoscopically than in those treated using laparotomy (55.6% <10 days vs. 0 by laparotomy, p = 0.01). There was also a tendency, although not significant, for a more rapid resumption of adjuvant chemotherapy in the laparoscopy group, with 57.1% resuming chemotherapy in <6 weeks compared to 42.9% in the laparotomy group (p = 0.52). ConclusionsThis study demonstrates the feasibility of HIPEC in a center with expertise in gynecological surgery when there is a suitable technical platform and close collaboration between the different teams involved. We also showed the first cases of HIPEC using laparoscopy, which seems to be a promising approach.

Clinical Characteristics and 8-year Survival Rate in Advanced Ovarian Cancer Following Neoadjuvant Chemotherapy: A Single Center Experience

Background: More than 75% of epithelial ovarian cancer (EOC) cases are diagnosed in advanced stages, which is associated with tumor recurrence and chemotherapy resistance. So far, to the best of our knowledge, a similar study has not been conducted in Iran to investigate the clinical characteristics and survival rate of these patients treated with neoadjuvant chemotherapy (NACT). Objectives: This study aimed to evaluate the clinical characteristics and survival of patients treated with NACT followed by cytoreductive surgery and the factors affecting survival. Methods: This retrospective cohort study was conducted on 147 advanced ovarian cancer cases who were treated with NACT referring to the Gynecology Oncology Department of Imam Khomeini Hospital in Tehran, Iran, between 2011 and 2021 and met the inclusion criteria for this study. The survival curve and Cox regression method were used to analyze the data. Results: The results revealed that 8.9% of advanced EOC (147/1,650) were treated with NACT and the average number of NACT courses was 4.12 periods. The survival rates of 1, 3, 5, and 8 years were 85.31%, 44.05%, 18.35%, and 13.77%, respectively. The mean and median of survival time were 47.7 and 36 months, respectively. Nearly 80% of the patients had stages 3C and 4A before receiving NACT. Based on the results of the adjusted Cox regression model, tumor marker level showed a significant relationship with survival rate (P=0.008), and also peritoneum involvement had a clinically significant impact on survival with a hazard ratio of 2.88. Conclusion: The results suggested that 8.9% of ovarian cancer cases were treated with NACT. It was also revealed that the average number of NACT courses was 4.12 periods and the 8-year survival rate was 13.77%. CA125 tumor marker level showed a significant relationship with survival rate, and peritoneum involvement had a clinically significant impact on survival.

Efficacy evaluation of albumin-bound paclitaxel combined with carboplatin as neoadjuvant chemotherapy for primary epithelial ovarian cancer

ObjectiveThis study aimed to compare the efficacy of albumin-bound paclitaxel combined with carboplatin (Nab-TC) with that of traditional solvent-based paclitaxel combined with carboplatin (TC) as neoadjuvant chemotherapy (NAC) regimens for primary epithelial ovarian cancer.MethodsEighty patients with advanced primary epithelial ovarian cancer admitted for treatment at the Harbin Medical University Cancer Hospital from January 2015 to January 2020 were retrospectively selected. All patients underwent surgery after 1–4 courses of NAC with Nab-TC or TC regimen. Among the patients included for study, 40 patients in each group.ResultsThe ORR in Nab-TC group was better compared to TC group (45% vs 40%), but the difference was not significant (P = 0.651). While the reduction rate of CA-125 value in the Nab-TC group was significantly better (P < 0.05). The postoperative complication rate such as postoperative blood transfusion (5% vs 35%) and postoperative infusion of human albumin (25% vs 55%) were significantly lower relative to the TC group. The median progression-free survival of the Nab-TC group was significantly longer relative to the TC group (20 months vs 13 months, P = 0.012), and the patient’s quality of life was also better in the Nab-TC group (P < 0.05). Our study demonstrated that Nab-TC regimen and R0 represented the independent prognostic factors.ConclusionThe efficacy of the Nab-TC regimen as NAC for advanced primary epithelial ovarian cancer was non-inferior to that of the TC regimen along with a lower incidence of adverse reactions, a longer PFS and a higher quality of life, supporting its therapeutic value in the clinic.

Can breast care nurses improve discussions had about fertility preservation?

Of the women who are diagnosed with breast cancer annually, around 7% are under the age of 40 (Paluch-Shimon, et at. 2017). Excluding trials, the National Breast Screening Programme in the United Kingdom starts at the age of 50, which means that younger women who present with a breast cancer are usually symptomatic and diagnosed at a later stage (Ribnikar et al, 2015) and due to this can be recommended a course of neo-adjuvant chemotherapy which commences promptly after diagnosis (Chollet-Hinton et al. 2016). Chemotherapy, among other treatments for breast cancer, are known to impact fertility which means it is of paramount importance that they are given the opportunity to discuss this in a timely manner with a fertility specialist (Paluch-Shimon et al, 2017). In the last ten years, only 55% of young women who commenced on treatments known to affect fertility were found to have been offered a referral to a fertility specialist at all (Banerjee and Tsiapali, 2016) and as few as 20.6% of young women were actually referred to discuss preservation (Goodman et al, 2012). Pennery (2015) conducted a study of 50 clinicians, of which 26% felt they did not have an appropriate referral pathway. Abe et al. (2016) found that clinicians felt that fertility preservation would delay breast cancer treatment and therefore did not prioritise preservation. Can breast care nurses assist in facilitating conversations around this topic, to enable informed decision making around the preservation of fertility?

CLO22-060: &gt; 3 Courses of Neo-Adjuvant Chemotherapy (NACT) May Affect Outcomes of Advanced Ovarian Serous Adenocarcinoma Patients

CLO22-060: &gt; 3 Courses of Neo-Adjuvant Chemotherapy (NACT) May Affect Outcomes of Advanced Ovarian Serous Adenocarcinoma Patients

CHRONO: randomized trial of the CHROnology of surgery after Neoadjuvant chemotherapy for Ovarian cancer

BackgroundIn patients treated for advanced ovarian cancer not suitable for complete primary surgery, interval surgery after three courses of neoadjuvant chemotherapy has been considered standard management since the EORTC randomized...

Abstract P1-08-03: Deep learning for early prediction of neoadjuvant chemotherapy response in triple negative breast cancers

Abstract Introduction: Neoadjuvant chemotherapy (NACT) is becoming standard of care for presurgical treatment of triple negative breast cancer (TNBC) patients. Achievement of pathological complete response (pCR) after NACT is associated with improved outcomes. There is currently an unmet need in development of imaging and clinical tools for prediction of pCR to NACT in TNBC. We investigated use of deep learning convolution neural networks (CNNs) for early prediction of pCR in a TNBC cohort on the basis of MRI acquired before the initiation and at the midpoint, after completion of four cycles of NACT (C4). Materials and Methods: Baseline and C4 MRIs of 112 TNBC patients were collected from an ongoing prospective clinical trial (NCT02276443). Four patients were excluded because they underwent different treatment for the second regimen. Among the 108 patients, 52 patients (48%) had pCR confirmed at surgery. Positive enhancement integral (PEI) derived from the early phases of DCE MRI, and apparent diffusion coefficients (ADC) derived from DWI MRI (b = 100 and 800 s/mm2), were used for our investigation. The images were aligned and the tumor regions were cropped from all images. All tumor patches were normalized between [0, 1], and were padded to form matrices of the same size of 192×192×64 for PEI, or the size of 192×192×16 for ADC. The CNN was constructed using stacked 3D convolution and MaxPooling layers. It consisted of up to four channels for the inputs (baseline and C4 PEI and ADC). Features extracted from each channel were concatenated and regressed for pCR prediction via three densely connected layers. Binary cross-entropy was used as the loss function for CNN training, and the loss was optimized using an Adam optimizer with the initial learning rate of 0.0001. Because of the currently limited sample size, four-fold cross-validation was used for CNN training and evaluation. The patients were divided into four groups, each group had 27 patients and the pCR:non-pCR ratio was controlled as 13:14. For each fold, one group was reserved as the independent testing group, and the other three groups were combined for network training and internal validation. Receiver operating characteristic (ROC) curve was plotted for each fold of testing, and area under the curve (AUC) was calculated. Final performance of the CNN was determined by averaging the AUCs of the four testing folds. Additionally, to test the prediction efficacy of each input, we trained the CNN under the same settings but used PEI or ADC only as input, and the results were compared. Results: The CNN trained with PEI only achieved an average AUC of 0.65 ± 0.09. The second CNN trained with ADC only achieved an average AUC of 0.72 ± 0.07. The third CNN trained with both PEI and ADC achieved an average AUC of 0.73 ± 0.06. Conclusion and Discussion: Using baseline and mid-treatment MRIs, deep learning CNN showed promising performance to predict pCR in the early course of NACT. The prediction AUC for the independent testing groups was largely improved by using ADC to train the network, indicating that ADC can have more critical information than PEI in assisting pCR prediction during the early course of NACT. Future work includes curation of a larger patient data for network training and evaluation to improve the prediction performance and further validate generalization of the network. We will also explore more advanced network structures, through which the prediction performance can be improved. Four-fold cross-validation AUCs of the network using different data as inputs.PEIADCPEI+ADCFold 10.570.640.66Fold 20.760.800.77Fold 30.660.700.68Fold 40.590.740.79Average0.65 ± 0.090.72 ± 0.070.73 ± 0.06 Citation Format: Zijian Zhou, Nabil A Elshafeey, David E Rauch, Beatriz E Adrada, Rosalind P Candelaria, Mary S Guirguis, Wei Yang, Medine Boge, Rania M Mohamed, Gary J Whitman, Deanna L Lane, Huong C Le-Petross, Jessica WT Leung, Lumarie Santiago, Marion E Scoggins, David A Spak, Miral M Patel, Frances Perez, Debu Tripathy, Vicente Valero, Clinton Yam, Stacy Moulder, Jason B White, Jong Bum Son, Mark D Pagel, Jingfei Ma. Deep learning for early prediction of neoadjuvant chemotherapy response in triple negative breast cancers [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 P1-08-03.

Abstract PD11-08: Associations of baseline breast MRI metrics and immune infiltration with chemotherapy response in triple negative breast cancer

Abstract Introduction: In triple-negative breast cancer (TNBC), both response to neoadjuvant chemotherapy (NAC) and the degree of pre-treatment (pre-tx) tumor immune infiltration as defined by tumor-infiltrating lymphocytes (TILs) are prognostic. Improving NAC response prediction in early TNBC would provide the opportunity to consider adjustments to the NAC regimen prior to initiating therapy. Breast magnetic resonance imaging (MRI) enables noninvasive whole-tumor measurement of microenvironment features. We investigated the value of pre-tx MRI metrics in addition to TILs for the prediction of NAC response in early TNBC patients. Methods: Women with Stage I-III TNBC who underwent pre-tx clinical breast MRI and NAC at our institution (2005-2019) were retrospectively identified. Response to NAC was noted, with pathologic complete response (pCR) defined as no residual invasive cancer present within the breast. When tissue was available, diagnostic biopsy was used to quantify pre-tx TILs as deciles from 10-100% by a breast pathologist. Patients underwent pre-tx breast MRI on either a 1.5T or 3T scanner including diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) MRI. From DCE-MRI, tumor longest diameter (LD) and T stage (1-4), as well as contrast kinetics including percent enhancement (PE) at 2 minutes post-contrast and signal enhancement ratio (SER) were determined. Tumor peak PE and peak SER (representing the highest mean PE and SER, respectively, for 3×3 voxel subregions) and functional tumor volume (FTV, tumor volume exhibiting PE ≥ 50%) were calculated. Mean apparent diffusion coefficient (ADC) was calculated from DW-MRI. TIL levels and imaging features were compared between pCR and non-pCR groups by Wilcoxon rank sum test and performance for prediction of pCR was evaluated using areas under the curve (AUC) measures from receiver operating characteristic curve analysis. Results: 115 TNBC patients (median age: 49, range 26-79 years) were evaluated, of which 45 (39%) achieved pCR. The majority received an anthracycline-containing regimen. Pre-tx TILs (evaluated in N=60 with available biopsy specimens) ranged from 10% to 80% (median, 10%) and were significantly higher in pCR vs. non-pCR patients (p = 0.02, AUC = 0.63). Pre-tx lesion size on imaging was predictive of response (Table 1), with pCR patients having significantly lower LD (p &amp;lt; 0.01, AUC = 0.68) and FTV (p = 0.01, AUC = 0.67). Peak PE was also associated with response, significantly lower in pCR patients (p = 0.04, AUC = 0.62), while SER and ADC were not (p &amp;gt; 0.05). Stratifying by T stage, both peak PE (p = 0.03) and FTV (p = 0.05) were predictive of response in T1/T2 patients, while no imaging metrics reached significance in T3/T4 patients. Discussion: In a large cohort of TNBC patients undergoing NAC, measures of tumor size and immune infiltration were strongly predictive of NAC response. Preliminary results suggest that baseline peak PE and FTV are associated with NAC response, particularly in earlier stage TNBC patients. These findings support the utility of imaging and TILs assessments to predict response in TNBC and potentially guide NAC regimens for improved outcomes. Future work will extend these analyses to assess the value of changes in imaging metrics over the course of NAC to predict response. Acknowledgments: NIH P30CA015704, R01CA248192, and Roger E. Moe Fellowship, ASCO/CCF Hayden Family Foundation Young Investigator Award in Breast Cancer Summary of imaging characteristics across TNBC cohort. Values indicate mean (standard deviation).Whole cohort. N=115T1/T2. N=80T3/T4. N=35pCR. N=45non-pCR. N=70pAUCpCR. N=39non-pCR. N=41pAUCpCR. N=6non-pCR. N=29pAUCLongest dimension (mm)34 (15)50 (27)&amp;lt;0.010.6829 (11)31 (10)0.410.5561 (6)76 (20)0.060.75FTV (cm3)14.7 (17.0)31.2 (43.4)0.010.6710.4 (11.0)19.0 (20.2)0.050.6446.1 (24.5)52.0 (58.0)0.720.57Peak SER1.77 (0.26)1.78 (0.23)0.960.501.76 (0.26)1.79 (0.23)0.690.531.91 (0.19)1.78 (0.26)0.270.68Peak PE (%)234 (61)268 (69)0.040.62237 (61)275 (71)0.030.66247 (70)256 (63)1.000.5ADC(×10-3 mm2/s)1.19 (0.29)1.31 (0.36)0.180.581.16 (0.28)1.24 (0.30)0.390.561.40 (0.30)1.4 (0.43)0.900.48 Citation Format: Anum S Kazerouni, Laura C. Kennedy, Michael Hirano, Bonny Chau, Debosmita Biswas, Shaveta Vinayak, Matthew J. Nyflot, Habib Rahbar, Suzanne Dintzis, Savannah C. Partridge. Associations of baseline breast MRI metrics and immune infiltration with chemotherapy response in triple negative breast cancer [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 PD11-08.

Abstract PD10-01: The PEARL trial: Pre-operative pembrolizumab with radiation therapy in early stage triple negative breast cancer

Abstract Background: Anti-PD(L)1 in addition to neoadjuvant chemotherapy (NAC) can achieve pathologic complete response (pCR) rates of up to 65% in patients with early stage triple negative breast cancer (TNBC). However, patients with non-pCR can have dismal prognosis. Innovative strategies that render the tumor microenvironment more sensitive to anti-PD(L)1 may confer benefit. Preclinical studies have shown that hypofractionated radiation therapy (RT) delivered to an in-situ breast tumor, when combined with immune checkpoint blockade, stimulates anti-tumor immune responses and induces long-term, tumor-specific memory. Here, we report the first results of a phase II study that established the feasibility and efficacy of this approach in the pre-operative treatment setting for TNBC. Methods: Fifty patients with stage I-III TNBC, defined as ER&amp;lt;10%,PR&amp;lt;10%, HER2-negative, were enrolled between 12/17-4/21. Study treatment consisted of one cycle (C1) of pembro (200 mg iv q 3wks), followed by cycle 2 (C2) of pembro + RT (24Gy) delivered to a breast primary, followed by NAC regimen per MD choice, surgery and adjuvant therapy. Paired tumor biopsies and blood were collected at 3 serial time points: 1) baseline (pre-treatment); 2) after pembro C1; 3) after pembro C2 + RT (prior to initiation of NAC). All patients received breast and axillary surgery and postoperative RT to the chest wall and regional lymph nodes. Dual primary endpoints were: 1) feasibility, defined by the number of patients who did not necessitate a &amp;gt;4-week delay in initiating NAC after pembro C2 + RT; 2) change in tumor infiltrating lymphocyte (TIL) score. Secondary endpoints included pCR, defined as ypT0/TisypN0, in addition to toxicity and cosmesis evaluations. Results: To date, 50 patients are evaluable with a median follow up of 12 months (range 6-12). Median age of cohort is 55y (range 26-76). The majority (92%) were clinical stage II; 2% stage I and 6% stage III. 34% of the cohort had biopsy-proven, node positive disease. All patients received a taxane, 52% carboplatin and 74% anthracycline. 12% did not complete the planned course of NAC due to toxicities. No patients experienced a delay in initiating NAC. 50% received breast-conserving surgery and 50% mastectomy. Grade 1 or 2 toxicities consisted of fatigue (76%), nausea (66%), maculopapular rash (32%), diarrhea (38%), colitis (2%), hypothyroidism (8%) and peripheral neuropathy (40%). Four patients had grade 3 toxicities that were attributable to pembro: hyponatremia(1), colitis (1), adrenal insufficiency(1) and pneumonitis (1). Three patients had grade 4 neutropenia which were not attributable to pembro. The overall rate of pCR was 74% (37/50). Among the 13 patients with non-pCR, 0% were RCB 1, 16% RCB 2 and 10% RCB 3. Among the 17 N+ patients, 13 converted to ypN0, 1 ypN1mic and 3 ypN1a. No patients progressed during treatment. Changes in TIL count, PD-L1 and other biomarkers after pembro +/- RT and their association with treatment response, will be presented at the meeting. Conclusions: The novel combination of pre-operative pembro followed by the addition of RT to pembro prior to NAC is not only feasible, but also achieves pCR rates that are higher-than-expected compared to the pembro arm of KEYNOTE-522. AEs were consistent with known safety profiles of each agent. If confirmed by larger, randomized studies, this combination will be paradigm-changing for the treatment of TNBC. Citation Format: Heather L McArthur, Stephen Shiao, Scott Karlan, Reva Basho, Farin Amersi, Michele Burnison, Amin Mirhadi, Alice Chung, Cathie T Chung, Catherine Dang, Heather Richardson, Armando E Giuliano, Nimmi Kapoor, Brigid Larkin, Hector Godinez, Samantha A Dunn, Negin Habibi Khameneh, Simon Knott, Philomena McAndrew, Monica Mita, Dorothy J Park, Christina Abaya, Jonathan H Chen, Amy Ly, Veerle Bossuyt, Alice Ho. The PEARL trial: Pre-operative pembrolizumab with radiation therapy in early stage triple negative breast cancer [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 PD10-01.

Long-term survival after definitive proton beam therapy for oligorecurrent esophageal squamous cell carcinoma: a case report

BackgroundRadical esophagectomy for esophageal squamous cell carcinoma has improved survival, but the rate of recurrence is high. Patients of recurrent esophageal squamous cell carcinoma after failure of chemotherapy have a poor prognosis. We herein report the achievement of long-term survival after definitive proton beam therapy for oligorecurrent esophageal squamous cell carcinoma after failure of chemotherapy.Case presentationA 60-year-old Japanese man was diagnosed as having squamous cell carcinoma of the lower thoracic esophagus (cT2N0M0, stage IIA). He underwent two courses of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, and esophagectomy with three-field lymphadenectomy was performed. Microscopic findings after resection showed two lymph node metastases (ypT2N1M0, stage IIB). Five months after resection, a computed tomography scan revealed a solitary liver metastasis in the S4 area. He underwent three courses of chemotherapy with cisplatin and 5-fluorouracil; however, positron emission tomography revealed two lymph node metastases. Surgeons recommended second-line chemotherapy, but the patient refused chemotherapy and requested proton beam therapy. We performed proton beam therapy without chemotherapy for the liver metastasis and lymph node metastases, with total doses of 79.2 and 60 Gy relative biological effectiveness, respectively, according to the tumor location. An acute side effect of grade 1 dermatitis occurred after proton beam therapy, but there was no acute or late complication of more than grade 2. The patient remains in complete remission 5 years after treatment without surgery or chemotherapy.Discussion and conclusionsProton beam therapy exerted a curative effect on oligorecurrent esophageal squamous cell carcinoma. This is the first report on the achievement of long-term survival after definitive proton beam therapy for oligorecurrent esophageal squamous cell carcinoma.

Multicenter randomised trial of two versus three courses of preoperative cisplatin and fluorouracil plus docetaxel for locally advanced oesophageal squamous cell carcinoma.

The optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating locally advanced ESCC in a multi-institutional, randomised, Phase II trial. We randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis. Patient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012-7.517). Two courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC. University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).

FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF, FLOT therapy for locally advanced esophageal carcinoma (JCOG1804E)—Short-term results for cohorts C and D.

286 Background: The standard neoadjuvant chemotherapy (NAC) in Japan for locally advanced esophageal squamous cell carcinoma (ESCC) consists of CDDP + 5-FU (CF). Recently, neoadjuvant DTX plus CF (DCF) therapy has shown promising efficacy for locally advanced ESCC. In addition, immune checkpoint inhibitors (ICIs) have demonstrated a survival benefit in ESCC and potential as an NAC in several cancers, including lung, breast, skin, and bladder. We previously reported that neoadjuvant CF plus nivolumab (Nivo) therapy was tolerable and showed promising efficacy for ESCC; however, the efficacy of ICI with DCF as an NAC and the safety of subsequent surgery for ESCC patients remain unclear. Methods: FRONTiER is a multi-cohort phase I study designed to evaluate the safety and efficacy of ICI combined with NAC in ESCC. The eligibility criteria were histologically proven ESCC with cT1N1-3M0 or cT2-3N0-3M0 (8th-UICC TNM classification), patient age of 20-75 years, PS ≤1, and no prior cancer therapies. The primary endpoint was the incidence of dose-limiting toxicities (DLT) from the initial dose to the 30th postoperative day. This study contained 5 experimental cohorts: cohort C received 3 courses of DTX (70 mg/m2), CDDP (70 mg/m2), and Nivo (360 mg/body) on day 1 and 5-FU (750 mg/m2) on days 1–5 every three weeks. Cohort D received one administration of Nivo (240 mg/body) 2 weeks before chemotherapy followed by the same regimen as cohort C. Results: Twelve patients were enrolled in cohort C (n = 6) and D (n = 6) (median age [range]: 60 [31-74] years, PS 0/1: 11/1, clinical stage I/II/III/IVA: 2/2/7/1). Only one patient in cohort D developed DLT (grade 3 dyspnea and rash); no other DLT were seen. Grade ≥3 adverse events were neutropenia (n = 1), leukopenia (n = 7), anorexia (n = 3), hyponatremia (n = 2), febrile neutropenia (n = 1), nausea (n = 1), and lymphopenia (n = 1) during NAC, and lung infection (n = 2), peritoneal infection (n = 1), anemia (n = 1), lymph leakage (n = 1), vagal reflex (n = 1), dyspnea (n = 1), rash (n = 1), septic shock (n = 1), pleural effusion (n = 1), and pneumatosis intestinalis (n = 1) during the postoperative period. No treatment-related deaths were observed. All patients received 3 courses of NAC, and 11 patients (91.7%) achieved an R0 resection without treatment interruption. One patient (16.7%) in cohort C and 3 patients (50.0%) in cohort D achieved pathological complete responses. Conclusions: Neoadjuvant DCF + Nivo with/without prior Nivo administration followed by surgery for locally advanced ESCC was well tolerated and showed an extremely promising efficacy. Clinical trial information: NCT03914443.