Start Of Neoadjuvant Chemotherapy Research Articles

Direct correlation of MR-DWI and histopathology of Wilms' tumours through a patient-specific 3D-printed cutting guide.

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) discourages invasive procedures to determine the histology of paediatric renal neoplasms at diagnosis. Therefore, the histological subtype of Wilms' tumours (WT) is unknown at the start of neoadjuvant chemotherapy. MR-DWI shows potential value as a non-invasive biomarker through apparent diffusion coefficients (ADCs). This study aimed to describe MR characteristics and ADC values of paediatric renal tumours to differentiate subtypes. Children with a renal tumour undergoing surgery within the SIOP-RTSG 2016-UMBRELLA protocol were prospectively included between May 2021 and 2023. In the case of a total nephrectomy, a patient-specific cutting guide based on the neoadjuvant MR was 3D-printed, allowing a correlation between imaging and histopathology. Whole-tumour volumes and ADC values were statistically compared with the Mann-Whitney U-test. Direct correlation on the microscopic slide level was analysed through mixed model analysis. Fifty-nine lesions of 54 patients (58% male, median age 3.0 years (range 0-17.7 years)) were included. Forty-four lesions involved a WT. Stromal type WT showed the lowest median decrease in volume after neoadjuvant chemotherapy (48.1 cm3, range 561.5-(+)332.7 cm3, p = 0.035). On a microscopic slide level (n = 240 slides) after direct correlation through the cutting guide, stromal areas showed a significantly higher median ADC value compared to epithelial and blastemal foci (p < 0.001). With a cut-off value of 1.195 * 10-3 mm2/s, sensitivity, and specificity were 95.2% (95% confidence interval 87.6-98.4%) and 90.5% (95% confidence interval 68.2-98.3%), respectively. Correlation between histopathology and MR-DWI through a patient-specific 3D-printed cutting guide resulted in significant discrimination of stromal type WT from epithelial and blastemal subtypes. Stromal Wilms' tumours could be discriminated from epithelial- and blastemal lesions based on high apparent diffusion coefficient values and limited decrease in volume after neoadjuvant chemotherapy. This may aid in future decision-making, especially concerning discrimination between low- and high-risk neoplasms. MR-DWI shows potential value as a non-invasive biomarker in paediatric renal tumours. The patient-specific cutting guide leads to a correlation between apparent diffusion coefficient values and Wilms' tumour subtype. Stromal areas could be discriminated from epithelial and blastemal foci in Wilms' tumours based on apparent diffusion coefficient values.

Impact of breast cancer neoadjuvant chemotherapy on plasma and urine amino acid profile, plasma proteins and nitrogen metabolism

Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of adverse effects. This pilot observational prospective study examined the effect of NAC using anthracycline + cyclophosphamide (AC) followed by paclitaxel (PTx) on a portfolio of 22 plasma and urinary amino acids, plasma proteins (albumin, prealbumin, transferrin), and products of nitrogen metabolism (urea, creatinine, uric acid) in plasma and urine. Plasma and 24-h urine samples were obtained from ten patients with early breast cancer (N1-3 N0-2 M0), at the following time points: before the start of NAC and during the AC/PTx treatment period (a total of 8 measurements at three-weekly intervals). Amino acids were analyzed using ion exchange chromatography. There were no significant differences in the measured parameters in plasma and urine between pre-NAC and during AC- and PTx-treatment. No trend was detected. A significant difference in the portfolio of plasma and urinary amino acids was found only in the pre-treatment period compared to the control group. Levels of eight plasma amino acids (8/22) were significantly reduced and those of nine urine amino acids were increased (9/22). Nitrogenous catabolites in plasma and urine were not indicative of increased protein catabolism during the anthracycline and taxane treatment periods. A slightly positive nitrogen balance was accompanied by an average weight gain of 3.3 kg (range 0–6 kg). The AC/PTx treatment regimen did not cause significant changes in the monitored laboratory parameters.

Venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer.

5552 Background: The primary objective was to assess the rate of venous thromboembolism (VTE) in patients with ovarian cancer who received neoadjuvant chemotherapy (NACT) following a quality improvement (QI) intervention of routine pharmacologic VTE prophylaxis compared to patients that did not receive prophylaxis. Methods: This is a retrospective cohort study of patients with pathologically confirmed ovarian cancer that received NACT between January 2009 to December 2021 from a single institution. Patients were excluded if VTE was diagnosed prior to initiating NACT. Routine pharmacologic VTE prophylaxis during NACT started in January 2017 following a QI initiative. VTE events were diagnosed by doppler scan of extremities or computed tomography of the chest ordered for symptomatic patients or diagnosed incidentally on routine treatment imaging. Patient factors and perioperative variates of interest were investigated for their association with VTE events through univariate and multivariate models. Results: A total of 290 patients with ovarian cancer received NACT and were included, with 106 of 290 patients (36.5%) receiving pharmacologic prophylaxis during NACT. Rate of VTE prophylaxis prior to the QI intervention was 3.68% (n=5) compared to 65.58% (n=101) after. The rate of VTE during NACT was 11.41% (n=21) without prophylaxis and 2.83% (n=3) with prophylaxis (p=0.013) (Table). The rate of any VTE event from the start of NACT through adjuvant chemotherapy was 20.11% (n=37) without prophylaxis and 4.72% (n=5) with prophylaxis (p&lt;0.01). There was no difference in adverse bleeding events in those that received prophylaxis to those that did not (0% vs 1.32%, p=0.239). On univariate analysis, VTE prophylaxis was associated with a decreased risk of VTE during NACT (OR 0.23; 95% CI: 0.06-0.78) and any VTE during primary treatment (OR 0.19; 95% CI 0.07-0.52). On multivariate analysis, VTE prophylaxis remained significantly associated with reduced VTE rates during NACT and during primary treatment (p=0.02 and p=0.001, respectively). Conclusions: Routine administration of pharmacologic VTE prophylaxis during NACT for patients with ovarian cancer is associated with reduced risk of VTE during NACT and throughout primary treatment and is not associated with adverse bleeding events. [Table: see text]

Abstract PD11-03: PD11-03 Comparison of a mono Atezolizumab window followed by Atezolizumab and chemotherapy with Atezolizumab and chemotherapy in triple negative breast cancer – an interim analysis of the adaptive randomized neoadjuvant trial NeoMono

Abstract Introduction: Improvement of systemic treatment of TNBC represents an unmet medical need. Targeted therapy of regulatory immune pathways has become an important option in the treatment of many malignant diseases including breast cancer. Neodjuvant trials combining chemotherapy and checkpoint inhibitors (KEYNOTE-522 and IMpassion031) have demonstrated a meaningful benefit regarding pathological complete remission (pCR) for the addition of PD-1- or PD-L1-inhibitors to chemotherapy in patients with TNBC. In the KEYNOTE-522 trial, the addition of an immune checkpoint inhibitor (ICI) to neoadjuvant chemotherapy also had a beneficial impact on event-free survival even in patients who did not achieve a pCR. Of note, in the neoadjuvant GeparNuevo trial only those patients with TNBC who received a 2-week checkpoint inhibitor monotherapy window before the start of neoadjuvant chemotherapy in combination with checkpoint inhibition, achieved a significant pCR benefit from the addition of the PD-1 inhibitor Durvalumab to neoadjuvant chemotherapy alone. Methods: NeoMono is a phase 2 randomized multicenter trial recruiting male and female patients with primary TNBC (defined as ER/PR &amp;lt; 10% and HER2 negative). Neoadjuvant treatment in Arm A and B consists of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant chemotherapy (i.e., 12 x Carboplatin and Paclitaxel q1w followed by Epirubicin and Cyclophosphamide q3w). Combination therapy in arm A is preceded by an Atezolizumab monotherapy window (i.e., 840 mg Atezolizumab once two weeks prior to initiation of combination therapy). Study goals are to compare the efficacy of neoadjuvant chemotherapy with Atezolizumab with and without an Atezolizumab two-week monotherapy window (primary endpoint: pCR) and the identification of biomarkers predicting (early) response to or resistance against Atezolizumab. The extensive translational program of the neoMono trial aims at identifying these biomarkers on tumor and patient level through analysis of sequential tissue and liquid biopsies. The NeoMono statistical design adapts the idea of a proof-of-concept trial and uses Bayesian posterior and predictive probabilities for inference about the primary hypothesis. Up to four planned efficacy interim analyses provide decision points for early stopping for success or futility. The expected maximum number of patients to be recruited is 458. Results: The predefined number of 50 patients in each arm being evaluable for the primary endpoint pCR has been reached and the results of the first planned interim analysis will be presented at the meeting. Conclusion: The addition of an ICI to state of the art neoadjuvant chemotherapy has recently been established as a new standard of care in TNBC. NeoMono has the potential to answer the question if the beneficial effect of the ICI can be increased by a chemotherapy free ICI monotherapy window prior to a combination with neoadjuvant chemotherapy. Citation Format: Hans-Christian Kolberg, Johannes Schumacher, Ramona Erber, Michael Braun, Bernhard Heinrich, Oliver Hoffmann, Peter A. Fasching, Georg Kunz, Michael P. Lux, Christian Schem, Eva-Maria Grischke, Mustafa Deryal, Kristina Lübbe, Arndt Hartmann, Sabine Kasimir-Bauer, Cornelia Kolberg-Liedtke. PD11-03 Comparison of a mono Atezolizumab window followed by Atezolizumab and chemotherapy with Atezolizumab and chemotherapy in triple negative breast cancer – an interim analysis of the adaptive randomized neoadjuvant trial NeoMono [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-03.

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

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

Incidence of venous thromboembolism in patients with advanced staged ovarian cancer undergoing neoadjuvant chemotherapy (411)

<b>Objectives:</b> Venous thromboembolism (VTE) during neoadjuvant chemotherapy (NACT) treatment for epithelial ovarian cancer (EOC) can delay interval debulking surgery (IDS) and affect overall prognosis. Our primary objective was to determine the incidence and timing of VTEs in patients with advanced-stage EOC who received NACT. Our secondary aims were to identify specific risk factors that increase the risk of VTE and assess the rate of direct-acting oral anticoagulants (DOACs) use for VTE treatment. <b>Methods:</b> Our retrospective cohort study included patients with stage IIIC/IV EOC who received NACT followed by IDS between January 2, 2012, and April 30, 2018, at a single institution. Patients were identified from a prospectively maintained surgical database of clinical, surgical, and outcomes data collected from the medical record. Medical records were reviewed to ascertain a prior history of VTE or the date of a clinical diagnosis of VTE between the EOC diagnosis and up to 180 days after IDS. VTE was defined as a deep vein thrombosis and/or pulmonary embolism diagnosed by Doppler ultrasound or computed tomography angiogram, respectively. Associations of patient characteristics with the development of VTE between EOC diagnosis and IDS were evaluated univariately using logistic regression. <b>Results:</b> Of the 160 patients who met the study inclusion criteria, five patients had a remote history of VTE prior to EOC diagnosis, and four had a concurrent VTE at time of diagnosis and thus were excluded from the analyses. Among the remaining 151 patients (mean age: 65.7 years), there were 29 (19.2%) incident cases of VTE between EOC diagnosis and the first 180 days after IDS: nine (6.0%) between EOC diagnosis and start of NACT, 13 (8.6%) during NACT and before IDS, and seven (4.6%) occurred within 180 days after IDS (Figure). Among these 29 patients, ten (34.5%) received a DOAC, specifically apixaban and rivaroxaban, for VTE treatment without complications. We were unable to identify any statistically significant associations between the following factors and the occurrence of VTE between EOC diagnosis and IDS: age, body mass index, smoking status, American Society of Anesthesiologists (ASA) score (>3 vs <3: odds ratio [OR]: 2.3, 95% CI: 0.7-7.2), Khorana score, and clinical tumor histology (non-serous vs serous: OR: 2.9, 95% CI: 0.7-12.4), or stage (IV vs IIIC: OR: 1.5, 95% CI: 0.6-3.8). <b>Conclusions:</b> Of the patients with advanced EOC who underwent NACT, 14.6% experienced a possible preventable VTE between EOC diagnosis and IDS. VTE during NACT can significantly delay IDS and affect the overall prognosis. Our results raise the need for further research to determine the population of patients who would benefit from thromboprophylaxis during NACT. The use of DOAC may be safe in this patient population.

Associations between fatigue and cellular metabolism in breast cancer patients: A longitudinal study

PurposeFatigue is frequently experienced during treatment for cancer and persists for months to years after treatment completion in a subset of patients. The underlying mechanisms remain poorly understood. We postulated that reduced cellular energy metabolism may underlie fatigue in cancer patients and survivors and tested this hypothesis in a sample of patients newly diagnosed with early-stage breast cancer (n = 49) followed for approximately 1 year from before the start of neoadjuvant chemotherapy (NACT) till after treatment completion. MethodsPatient-reported fatigue was assessed with the Checklist Individual Strength, and blood samples were obtained before, during, and shortly after NACT. A final assessment was completed after surgery and radiation therapy, 4–6 months after NACT. At each study time point, mitochondrial oxygen consumption and glycolytic activity were measured in peripheral blood mononuclear cells (PBMC). Associations of these measures of PBMC energy metabolism with fatigue were assessed in multilevel models. ResultsBefore NACT, higher mitochondrial oxygen consumption and glycolytic activity were associated with higher fatigue, whereas after completion of all primary treatment, these assessments were associated with lower fatigue. ConclusionThese findings suggest that lower cellular energy metabolism after treatment may be a novel target for interventions aimed at preventing or reducing persistent fatigue. Earlier studies investigated the use of supplements for maintaining mitochondrial health during treatment, with mixed results; when proven to be safe, such interventions may be more effective after treatment and in individuals with reduced mitochondrial oxygen consumption rates.

Association of pre-treatment hemoglobin levels with survival outcomes among Indian women with triple negative breast cancer.

e12549 Background: Prevalence of Triple Negative Breast Cancer (TNBC), which has utterly poor prognosis and higher recurrence rate, is high among Indian women ranging from 20-43% across different regions of India. Previous studies from other countries have shown that pretreatment hemoglobin and hematocrit values influence treatment outcomes among breast cancer patients. Recent 2019-2020 National Family Health Survey (NFHS) of India reported that 66.4% of women suffer from anemia. This study examined the association of pre-treatment hemoglobin levels with survival outcomes among Indian women with TNBC. Methods: We retrospectively analyzed the medical records of 435 women registered at our institute with a diagnosis of TNBC between the years 2013-2021. Pre-treatment hemoglobin levels i.e. either before the start of neoadjuvant chemotherapy (NACT) or prior to surgery among those who received adjuvant chemotherapy were retrieved from the medical records along with clinical and tumor characteristics. Primary outcomes were relapse free survival (RFS) and overall survivals (OS). Cox-regression and Kaplan-Meier survival analysis were used to examine the association of pre-treatment anemia with survival outcomes in these patients. Results: Fifty-one percent (n=221) of the 435 TNBC patients in our study cohort had pretreatment hemoglobin level of &lt;12.0 g/dL (based on the World Health Organization criteria). 278 patients received NACT and pathological complete response (pCR) rates were similar in anemic (31.5%) and non-anemic groups (30.1%). When adjusted for clinical and other hematological parameters, anemia was not associated with pCR. Median follow-up of the study cohort was 22.9 months (Range: 2.6 to 92.7 months). Pre-treatment anemia was significantly associated with poor RFS when adjusted for clinical and hematological parameters [adjusted Hazard ratio (aHR) (95%CI): 1.53 (1.02-2.31)]. Median RFS was 52.5 months among the anemic group and was not reached in non-anemic group. Effect of anemia on RFS did not vary by age category or menopausal status. However, the effect of anemia on OS varied significantly by menopausal status. Menopausal women with anemia at time of diagnosis had significantly higher hazard of death compared to menopausal women without anemia [aHR (95%CI): 5.0 (1.15-21.66)] and this association was not observed in pre-menopausal women [aHR (95%CI): 0.53 (0.19-1.44)]. Conclusions: Pretreatment hemoglobin level of &lt;12g/dL was associated with poor survival outcomes among Indian women with TNBC and the effect of anemia on overall survival of these patients varied by menopausal status. Evaluation of hemoglobin levels during chemotherapy, pre-post surgery, and at various stages of follow-up is needed to determine the independent association of hemoglobin level trajectories with treatment outcomes and long-term survival among these TNBC patients.

A population-based study on treatment and outcomes in patients with gastric adenocarcinoma diagnosed with distant interval metastases

BackgroundIn patients with gastric or gastroesophageal junction (GEJ) cancer treated with curative intent, distant interval metastases may be detected after start of neoadjuvant chemotherapy or during surgery. The aim of this study was to explore characteristics, allocated treatment and overall survival (OS) in gastric/GEJ cancer patients with interval metastases, and to compare OS with synchronous metastatic gastric/GEJ cancer patients who started palliative chemotherapy. MethodsPatients with interval metastases were selected from the Netherlands Cancer Registry by including patients with potentially curable gastric/GEJ adenocarcinoma (2010–2018) who started chemotherapy without concurrent radiotherapy. The OS since start of neoadjuvant treatment of patients with interval metastases was compared with a propensity score-matched cohort of patients with synchronous metastases who received palliative systemic treatment. Results164 patients with interval metastases diagnosed in 2010–2018 were included. Metastases were most frequently detected during surgery (83%) and most frequently located in the peritoneum (77%). Peritoneal interval metastases were observed in 63% and 80% of the patients who did and did not have a diagnostic laparoscopy prior to neoadjuvant treatment, respectively (P = 0.041). Median OS was 8.9 months (IQR 5.5–13.4), compared to 8.0 months (IQR 4.1–14.1) in matched synchronous metastatic patients calculated from start of neoadjuvant and palliative systemic treatment, respectively (P = 0.848). ConclusionThis population-based study shows that gastric/GEJ cancer patients who started neoadjuvant treatment and were diagnosed with interval metastases most frequently suffered from peritoneal metastases detected during (exploratory) surgery, even when a diagnostic laparoscopy was performed before start of treatment. OS was comparable to patients with synchronous metastatic gastric/GEJ cancer.

Abstract OT2-29-01: neoMono - An adaptive randomized neoadjuvant two arm trial in patients with TNBC comparing a mono atezolizumab window followed by atezolizumab and chemotherapy with atezolizumab and chemotherapy

Abstract Background: Improvement of systemic treatment of TNBC represents an unmet medical need. Recently, targeted therapy of regulatory immune pathways has become an important option in the treatment of numerous malignancies including breast cancer. Neoadjuvant trials combining chemotherapy and checkpoint inhibitors (KEYNOTE-522 and IMPASSION031) have demonstrated a meaningful benefit regarding pathological complete remission (pCR) and event-free survival (EFS) for the addition of PD-1- and PD-L1-inhibitors to chemotherapy among patients with TNBC, respectively. In addition, initial analyzes have presented promising results regarding event-free survival. In the neoadjuvant GeparNuevo trial only a subgroup of patients with TNBC, receiving a 2-week checkpoint inhibitor monotherapy window before the start of neoadjuvant chemotherapy in combination with checkpoint inhibition, achieved a pCR benefit as compared to patients treated with neoadjuvant chemotherapy alone. Trial Design: NeoMono is a phase 2 randomized multicenter trial recruiting male and female patients with primary TNBC (defined as ER/PR &amp;lt; 10% and HER2 negative). Neoadjuvant treatment in Arm A and B consists of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant chemotherapy (i.e. 12 x Carboplatin and Paclitaxel q1w followed by Epirubicin and Cyclophosphamide q3w) In Arm A this therapy is preceded by Atezolizumab 840 mg q2w (Atezolizumab mono window). Study goals are the comparison of efficacy and safety of neoadjuvant chemotherapy with Atezolizumab with and without Atezolizumab two-week window (primary endpoint: pCR) and the identification of biomarkers predicting (early) response to or resistance against Atezolizumab. The broad translational program of the neoMono trial aims at identifying these biomarkers on tumor and patient level. The neoMono statistical design adapts the idea of a proof-of-concept trial and uses Bayesian posterior and predictive probabilities for inference about the primary hypothesis. Up to four planned efficacy interim analyses provide decision points for early stopping for success or futility. The expected maximum number of patients to be recruited is 458. Citation Format: Cornelia Kolberg-Liedtke, Johannes Schumacher, Ramona Erber, Michael Braun, Bernhard Heinrich, Oliver Hoffmann, Peter Fasching, Helmut Forstbauer, Anke Kleine-Tebbe, Georg Kunz, Michael Lux, Joachim Rom, Christian Schem, Nicole Stahl, Arndt Hartmann, Sabine Kasimir-Bauer, Hans-Christian Kolberg. neoMono - An adaptive randomized neoadjuvant two arm trial in patients with TNBC comparing a mono atezolizumab window followed by atezolizumab and chemotherapy with atezolizumab and chemotherapy [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 OT2-29-01.

A Case of Small Intestinal Perforation During Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer

Background: For patients with locally advanced rectal cancer, side effects such as nausea, vomiting and loss of appetite may occur during neoadjuvant chemotherapy, but small intestinal perforation is very rare. Case: We present a case of a 62-year-old man who suffered small intestinal perforation in the first cycle neoadjuvant treatment of locally advanced rectal cancer with capecitabine and oxaliplatin. Six days after the start of neoadjuvant chemotherapy, he began to develop intermittent abdominal pain, accompanied by diarrhea and abdominal distension. The CT scan revealed an abscess with free air in the pelvic cavity with proximal intestinal ileus. Then we performed a laparotomy. After enterolysis, the rectum with tumor was carefully examined with no perforative lesion, and the terminal ileum about 15cm from the ileocecum which adhere to the pelvic abscess had one about 0.8cm ulcer. The patient had a radical anterior resection and the morbid small bowel resection with protective ileostomy. The postoperative pathological examination showed the full-thickness necrosis of the intestinal wall in the ileal lesion with peripheral acute suppurative inflammation. AND the final pathological stage of the tumor was pT3N0M0 (American Joint Committee on Cancer, eighth edition). Conclusion: As a chemotherapy regimen based on fluorouracil and oxaliplatin, small intestinal perforation is a very rare complication. The most common complications of these two drugs are gastrointestinal symptoms such as diarrhea. Therefore, when the complications are not relieved during chemotherapy, we should think of a more serious possibility

Safety of pre- or postoperative accelerated radiotherapy in 5 fractions: A randomized pilot trial.

ObjectiveNeo-adjuvant radiotherapy (NART) for breast cancer has shown promising survival results in retrospective trials. However, there are some obstacles such as a chemotherapy delay, an increased overall treatment time (OTT) and the risk of increasing surgical morbidity. Accelerated radiotherapy (RT) in 5 fractions allows to deliver NART in a very short time span and minimizes the delay of surgery and chemotherapy. This trial investigates this NART schedule for safety, feasibility and OTT.Material and methodsTwenty patients eligible for neo-adjuvant chemotherapy (NACT) and breast conserving surgery, were randomized between NART before NACT or NACT and postoperative RT. In both arms, RT treatment was given in 5 fractions to the whole breast with a simultaneously integrated boost (SIB) on the tumor(bed). Lymph node irradiation was given concomitantly in case of lymph node involvement. OTT was defined as the time from diagnosis to last surgery in the intervention group, while in the control group the time between diagnosis and last RT-fraction was used. In the intervention group NACT-delay was defined as time between diagnosis and start of chemotherapy.Results20 patients were included, and 19 patients completed treatment. OTT was significantly shorter in the intervention group (mean 218 days, range 196–253) compared to the control group (mean 237, range 211–268, p = 0.001). The difference in mean duration from diagnosis to the first treatment was a non-significant 4 days longer (31 vs 27 days, p = 0.28), but the start of NACT after diagnosis was delayed by 21 days (48 vs 27 days, p < 0.001). NART did not result in additional surgery complications.ConclusionThis pilot trial is the first to report on accelerated NART in 5 fractions with SIB. NART before NACT resulted in a shorter OTT with good safety results.

Venous thromboembolism in women with ovarian cancer undergoing neoadjuvant chemotherapy prior to cytoreductive surgery: A retrospective study

Ovarian cancer is associated with a venous thromboembolism risk of at least 7.2% by 2years from diagnosis, and although patients undergoing surgery benefit from routine thromboprophylaxis, those undergoing neoadjuvant chemotherapy do not. This study aims to determine the venous thromboembolism incidence in patients with ovarian cancer undergoing neoadjuvant chemotherapy, and explore whether any subset is at higher risk, in order to evaluate whether thromboprophylaxis is justified in some or all of these patients. This was a retrospective review of all women undergoing neoadjuvant chemotherapy for FIGO radiological stages III and IV primary ovarian, fallopian tube, and primary peritoneal cancer, between 2000 and 2015, in a London tertiary cancer center. The primary outcome was venous thromboembolism rate among women undergoing neoadjuvant chemotherapy. The secondary outcomes were patient or treatment factors associated with venous thromboembolism risk, including age, body mass index, smoking status, performance status, and tumor stage. We identified 278 eligible women from the ovarian cancer database. Fifty-eight women (20.9%) developed venous thromboembolism between initial presentation and the immediate postoperative period, of which 45 (77.6%) developed a pulmonary embolism. In all, 15.1% of women developed venous thromboembolism from the start of neoadjuvant chemotherapy. Age, body mass index, smoking, or other comorbidities were not significantly associated with venous thromboembolism risk. One woman died from massive pulmonary embolism, 27 women underwent inferior vena cava filter insertion, and 10 had surgery delayed. This study demonstrates an unacceptably high rate of avoidable venous thromboembolism including pulmonary embolism in these women, which complicates and delays treatment. Thromboprophylaxis during neoadjuvant chemotherapy should now be assessed prospectively.

Diffusion-weighted imaging or MR spectroscopy: Which to use for the assessment of the response to chemotherapy in breast cancer patients?

BackgroundDiffusion-weighted MRI (DWI) and MR spectroscopy (MRS) both are noninvasive MR sequences that could be used as a reliable tool to assess the functional behavior of the breast cancer. The aim of the study was to assess the value of DWI and MRS in predicting the early response to neo-adjuvant chemotherapy (NAC) and absence of residual disease after treatment.ResultsOne hundred thirty-three patients diagnosed with breast cancer and scheduled for NAC were enrolled in this study. All lesions were subjected to qualitative and quantitative analysis of DCE-MRI, DWI and MRS, where the lesions size, kinetic parameters, ADC values and MRS choline peak were recorded before the start of NAC and after completion of chemotherapy. The results of each MRI modality were correlated with the findings that were found at the pathology report of the complete surgical specimen. The sensitivity and specificity of the MR modalities to predict pathological complete remission post-NAC were 73.68% and 83.33%, respectively, using the kinetic curve pattern, 78.95% and 83.33%, respectively, using the ADC value and finally 78.95% and 91.67%, respectively, using the MRS choline peak. Similar sensitivity (89.47%) to predict pathological complete remission was presented by the ADC value and the MRS choline peak together when compared to the ADC value and dynamic curve patterns.ConclusionDWI and MRS are valuable MRI techniques and their accuracy in detecting residual disease is almost similar to that of DCE MRI. The inclusion of these sequences in the imaging protocol of NAC candidates improve monitoring of the response to treatment and allow early distinction between complete, partial and non-responders' cases in breast cancer patients.

Exploratory Analysis of 18F-3'-deoxy-3'-fluorothymidine (18F-FLT) PET/CT-Based Radiomics for the Early Evaluation of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer.

PurposeThe objective of this study was to evaluate a set of radiomics-based advanced textural features extracted from 18F-FLT-PET/CT images to predict tumor response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (BC).Materials and MethodsPatients with operable (T2-T3, N0-N2, M0) or locally advanced (T4, N0-N2, M0) BC were enrolled. All patients underwent chemotherapy (six cycles every 3 weeks). Surgery was performed within 4 weeks of the end of NCT. The MD Anderson Residual Cancer Burden calculator was used to evaluate the pathological response. 18F-FLT-PET/CT was performed 2 weeks before the start of NCT and approximately 3 weeks after the first cycle. The evaluation of PET response was based on EORTC criteria. Standard uptake value (SUV) statistics (SUVmax, SUVpeak, SUVmean), together with 148 textural features, were extracted from each lesion. Indices that are robust against contour variability (ICC test) were used as independent variables to logistically model tumor response. LASSO analysis was used for variable selection.ResultsTwenty patients were included in the study. Lesions from 15 patients were evaluable and analyzed: 9 with pathological complete response (pCR) and 6 with pathological partial response (pPR). Concordance between PET response and histological examination was found in 13/15 patients. LASSO logistic modelling identified a combination of SUVmax and the textural feature index IVH_VolumeIntFract_90 as the most useful to classify PET response, and a combination of PET response, ID range, and ID_Coefficient of Variation as the most useful to classify pathological response.ConclusionsOur study suggests the potential usefulness of FLT-PET for early monitoring of response to NCT. A model based on PET radiomic characteristics could have good discriminatory capacity of early response before the end of treatment.

Impact of angiotensin inhibitors on pathologic complete response with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC).

432 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis, cell proliferation, desmoplasia and immunosuppression. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) may have antitumor effects partly by inhibiting transforming growth factor (TGF)-β, a major resistance mechanism in bladder cancer. Methods: Patients (pts) with muscle invasive bladder cancer (MIBC) treated or not treated with ACEi/ARB while receiving preceding radical cystectomy (RC) were assessed for pathologic complete response (pCR) defined as pT0N0 and overall survival (OS). Pathologic features, performance status, clinical stage, type and number of cycles of NAC, and presence of grade ≥3 toxicities were collected retrospectively. The Kaplan-Meier method was used to estimate overall survival (OS). Logistic and Cox regression was used to explore factors potentially prognostic for pCR and OS respectively. Results: 187 patients received NAC followed by RC. The mean age at the time of NAC was 65. 71% were male and 29% were female. Of the 187 patients, 61% received Cisplatin/Gemcitabine and 28.3% received dose dense MVAC. Of patients receiving NAC, 53 (28%) had a pCR. The 5-year OS was 64%. There were 41 (21.9%) patients taking an ACEi and 24 (12.8%) patients taking an ARB at the start of NAC. Of the 41 patients who took an ACEi, 17 (41.5%) had a pCR; of the 146 patients who did not take an ACEi, 36 (24.7%) had a pCR. ACEi intake during NAC was the only factor associated with pCR on multivariable analysis (odds ratio of 2.17 [95% CI 1.05-4.48] p = 0.037). pCR was the only factor shown to be associated with significantly improved OS (Hazard Ratio 0.18 [95% CI 0.07-0.45] p = &lt; 0.001). After adjusting for pCR, ACEi was not significantly prognostic of OS (HR = 1.12, 95% CI = 0.60 to 2.09, p = 0.72). ARB intake while receiving NAC was not associated with pCR or OS. Conclusions: ACEi intake was associated with significantly increased pCR in patients with MIBC receiving NAC, and pCR was the only significant factor associated with OS. We hypothesize that ACEi may augment the activity of NAC and increase pCR, which translates to improved OS. ACEi intake was not associated with improvement in OS potentially due to competing causes of mortality in patients requiring ACEi. Our data requires validation.

Abstract PS1-46: Magnetic seeds to aid targeted axillary dissection

Abstract Introduction: Indications for accurate removal of a previously identified, involved or highly suspicious axillary lymph node include: 1) after neoadjuvant chemotherapy (NACT) to ensure pathological assessment of the correct index node (targeted axillary dissection, TAD) 2) for women with an abnormal/indeterminate node on imaging who may be able to avoid axillary lymph node clearance (ALNC) because they meet Z0011 criteria or may be eligible for POSNOC trial inclusion 3) guided removal of a specific axillary lymph node (eg Rotter’s node recurrence, diagnostic biopsy, inclusion of specific node in ALNC). Dual localisation is either not viable or has an unacceptably high false negative rate in these scenarios and marking of the index node is advised. Although conventional markers are often used prior to NACT, finding that marked node at surgery can pose a challenge. Wire localisation has variable outcomes and scheduling constraints. Magnetic seed localisation, with MagseedTM, allows for easy placement and excision of targeted nodes. Seeds can be accurately placed, do not migrate and can now be placed many months prior to surgery, at the start of NACT. The aim of this study was to report our early experience. Methods: Patients were identified by searching an imaging database for women who had undergone ultrasound (US)-guided MagseedTM insertion into an abnormal axillary lymph node between August 2018 and July 2020. Data on intended use and surgical outcomes were collected retrospectively from electronic patient records (EPR). Patients were categorised into 3 groups as described above. Results: 37 patients were identified, 17 in group 1, 13 in group 2 and 7 in group 3. Only 1 patient had complications with MagseedTM insertion, requiring a second attempt to successfully mark the required node. In 1 patient the MagseedTM was found on the surgical drape, thought to have been lying adjacent to the node intended for excision, this patient was therefore excluded from further evaluation in the results, as were 3 patients with missing data. One patient has yet to come to surgery, all other MagseedsTM have been successfully retrieved. Group 3 indications were disparate, and this group will not be described further. Group 1 - in 10 of 15 patients post NACT the MagseedTM-marked node was found to be the sentinel node by routine mapping techniques (Technetium 99 +/- Patent V blue dye injection), identified as either hot or hot and blue. Of the 15 patients, 6 remained node positive on intra-operative assessment and underwent ALNC whilst 9 (60%) were spared ALNC. 2 patients avoided false negative results as the Magseed™-marked node contained residual disease yet was neither hot nor blue. Group 2 - Ten patients underwent sentinel lymph node biopsy using routine mapping techniques and MagseedTM-guided excision of a specifically targeted node. In 7 the MagseedTM-marked node was found to be a sentinel node (hot or hot and blue). Only 3 patients had sufficient disease to warrant completion ALNC. Conclusion: Insertion of a magnetic seed into a biopsy-proven positive node prior to planned TAD or into an abnormal node identified at diagnosis facilitates specific node retrieval for pathological assessment, with minimal associated complications, and has wide versatility. Magnetic seed localisation reduces the false negative rate and provides confidence in the correct assessment of the axilla thereby sparing patients unnecessary ALNC if they have had a complete pathological response to NACT or have limited axillary disease. The ability to insert the seed prior to the surgical date allows for flexibility with scheduling in comparison to wire localisation. Citation Format: Kathryn E Harborough, V Sinnett, K Downey, K Krupa, J E Rusby, P A Barry. Magnetic seeds to aid targeted axillary dissection [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-46.

Role of positron emission tomography in predicting early tumor response to neoadjuvant chemotherapy for breast cancer

Background. Neoadjuvant chemotherapy (NACT) is an important stage in the treatment of patients with breast cancer. Positron emission tomography/computed tomography (PET/СT) with fluorodeoxyglucose labeled with 18F (18F-FDG) is widely used as an effective method of metabolic tumor imaging at the stages of treatment. The aim of this study was to evaluate the possibility of using PET/CT with 18F-FDG to determine the early tumor response to NACT.Materials and methods. The results of PET/CT with 18F-FDG in 27 patients with breast cancer were retrospectively analyzed. The study was performed before the start of NACT, after the 2nd cycle of chemotherapy and after completion of all courses, the maximum accumulation of 18F-FDG in the tumor tissue (SUVmax), as well as the dynamics of changes in SUVmax after NACT (SUV(%)) were assessed. According to the results of postoperative morphological examination, the patients were divided into two groups: with complete tumor regression (pCR) and with no complete tumor regression (non-pCR).Results. The results of the study showed that the SUV(%) between the primary and interim examination, as well as between the intermediate and preoperative PET/CT scans, was 66.6 ± 13.3 % and 31.6 ± 17.5 %, respectively. The dynamics of SUV(%) between the primary and intermediate scans in the pCR and non-pCR groups was 79.04 ± 4.1 % and 63.8 ± 13.1 %, respectively (p = 0.02). The SUVmax value in the pCR and non-pCR groups during the primary PET/CT scan was 8.5 ± 0.78 and 8.2 ± 0.78, respectively (p = 0.5), while the intermediate scan was 1.8 ± 0.35 and 3.0 ± 0.14 (p = 0.03). Based on the research results, an ROC analysis was carried out, which showed that the optimal value of SUV(%) is 73.55 %, which showed the highest sensitivity and specificity.Discussion. Given that the change in SUVmax between primary and intermediate PET/CT was more pronounced than between intermediate and preoperative scans, it can be assumed that metabolic changes in the background of NACT are observed already in the early stages of treatment and persist until the end of therapy, thus, the ineffectiveness of the chemotherapy regimen can be determined using an intermediate PET/CT scan and a timely change in the treatment plan.Conclusions. We consider 73.55 % to be the optimal value of SUV(%) for intermediate PET/CT scanning; for this indicator and above, it is expected to expect a complete morphological response of the tumor to NACT. We believe that PET/CT with 18F-FDG at an intermediate stage of observation during NACT is a valuable method for predicting early tumor response to therapy.

Optimal timing of radical cystectomy after neoadjuvant chemotherapy in muscle invasive bladder cancer (MIBC).

509 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with bilateral pelvic lymph node dissection is the current standard of care for MIBC. Pathologic downstaging with NAC is an important surrogate endpoint and associated with overall survival benefit. There have been questions about the impact of delay in definitive surgery because of NAC. The optimal timing of surgery from the start of NAC is uncertain. We studied this question using National Cancer Database (2004-2015). Methods: We identified patients with MIBC (cT2-T4aN0M0 &amp; cT1-T4aN1M0) who received NAC within 6 months of diagnosis and underwent surgery between 10 weeks and 9 months of the start day of NAC. We excluded patients who died within 30 days of surgery. Time period was stratified into three cohorts; 11-16, 17-24, and ≥25 weeks from the start day of NAC. Descriptive analysis, Kaplan-Meier plots, Log-Rank tests for univariate and proportional hazards models for multivariate survival analyses were performed. Results: 3709 patients were identified; 75% were males, 77% cases were cT2 and 73% had charlson-deyo score (CS) of '0'. Median time for surgery 10 weeks after start of NAC was 118 days. Forty-two (42%) had surgery in 11-16, 47% in 17-24 and 9.9% in ≥25 weeks. Majority (60%) were treated at academic and 24% at comprehensive community. Only 29% achieved complete pathological complete response rate (Tis or T0). On univariate analysis receiving NAC within 3 months of diagnosis was significantly associated with survival benefit (p &lt; 0.001). Cox-regression results showed that patients who underwent surgery in 11-16 and 17-24 week time period had significantly better survival than &gt; 25 week group with HR of 0.84 (0.71- 0.98) and 0.82 (0.70-0.97) respectively. In addition patients with CS of '0' had better survival with HR 0.78 (0.62-0.90) and &gt; 75 years of age was associated with worse survival HR 1.73 (1.35-2.22). Conclusions: Our study indicates that appropriate patients with MIBC benefit from receiving surgery within 24 weeks of starting NAC. However, randomized prospective study is warranted to further explore the role of delay of surgery from NAC.

Abstract P4-01-12: The association of circulating tumor cells with tumor response in breast cancer patients undergoing neoadjuvant chemotherapy

Abstract Introduction Despite its limitations, Cellsearch® remains the only validated technique to detect circulating tumors cells (CTCs) in the peripheral blood of cancer patients. A new technique (CytoFind) allows trapping CTCs with varied numbers of antigen-targeted magnetic particles to be trapped in different compartments of a fluidic chip based on their level of expression and velocity, allowing the detection and count of CTC subpopulations (profiling-based technique). Additionally, this technique is able to use different capture agents for binning and profiling beside the EpCAM expression. We used magnetic nanoparticles tagged with anti-Her2 in a new microfluidic device to capture CTCs (Her2 technique). We aimed to prospectively assess the performance of this new technology compared to Cellsearch® and evaluate the association of CTCs with tumor response in breast cancer patients on neoadjuvant chemotherapy. Methods Breast cancer patients who underwent neoadjuvant chemotherapy followed by surgery were eligible. CTCs were enumerated before the start of neoadjuvant chemotherapy. The concordance of CTC detection between techniques was assessed with the intraclass correlation coefficient (ICC). The association between CTCs and baseline characteristics as well as tumor response was evaluated with a Fisher exact test. Tumor response was assessed as pathologic complete response (pCR) and with the residual cancer burden index (RCB). Results Thirty-five patients were successfully assessed for CTCs using at least one technology. Fifty four percent and 23% of the patients had a HER2 positive and triple negative disease respectively. Thirty eight percent and 53% of the patients had a pCR and a good tumor response rate (RCB 0 or 1) respectively. The mean CTC count detected was 0.63 (SD 1.8), 0.71 (SD 1.51) and 1.22 (SD 1.62) with Cellsearch®, profiling-based and Her2 technologies respectively. An association was seen between detected CTCs and tumor size as well as progesterone receptor status (p&amp;lt;0.05) but not with the rest of the baseline characteristics: age, estrogen receptor, Her2, or nodal status, tumor grade and presence of lymphovascular invasion (p&amp;gt;0.05). No association was found between CTC counts and tumor response (pCR or RCB). The profiling-based and Her2 technologies were moderately concordant (ICC=0.5) but a low concordance with Cellsearch® was observed (ICC=0.07). Conclusions A new profiling-based technology detected CTCs in breast cancer patients and may overcome the Cellsearch® limitations and provide more information on CTCs subpopulations. Yet, further calibration and validation are needed before using this technology in future research. While no association between CTCs and tumor response was observed, a longer follow up is needed to assess the impact on survival. Citation Format: Jacques Raphael, Reza Mohamadi, Alex Kiss, Maureen Trudeau, Sunil Verma, Alison Allan, Shana Kelley, Joelle Helou, Fang-I Lu, Siqi Zhu, Kathleen I Pritchard. The association of circulating tumor cells with tumor response in breast cancer patients undergoing neoadjuvant chemotherapy [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 P4-01-12.