Predictors Of Complete Response Research Articles

What Predicts Complete Response to Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer?

Total neoadjuvant therapy in the treatment of stage II and III rectal cancer involves the administration of either induction or consolidation chemotherapy with chemoradiation before surgery. Total neoadjuvant therapy is associated with an increased complete response rate, which is defined as the proportion of patients who either had a pathological complete response after surgery or sustained a clinical complete response for at least 1 year under surveillance. To identify the predictors of complete response to total neoadjuvant therapy and compare different diagnostic tools in predicting complete response. Retrospective cohort study. A single tertiary care center. Patients with stage II and III rectal cancer who were diagnosed between January 2015 and December 2021. Total neoadjuvant therapy. Complete response rate, predictors of complete response, sensitivity and specificity of sigmoidoscopy, and MRI in predicting complete response. One hundred nineteen patients (mean age 56 [±11.3] years, 47 [39.5%] women, 100 [84%] stage III rectal cancer) were included. The median tumor size was 5.1 (4-6.5) cm, and 63 (52.9%) were low rectal tumors. Twenty-one patients (17.6%) had extramural vascular invasion and 62 (52.1%) had elevated CEA at baseline. One hundred eight patients (90.8%) received consolidation chemotherapy. After total neoadjuvant therapy, 88 of 119 patients (73.9%) underwent surgery, of whom 20 (22.7%) had pathological complete response. Thirty-one patients (26.1%) underwent watch-and-wait, of whom 24 (77.4%) had sustained clinical complete response. Overall, the complete response rate was 37%. Low rectal tumors (OR 1.5 [95% CI, 1.03-2.4], p = 0.04) and absence of extramural vascular invasion (OR 2.2 [95% CI, 1.1-5.6], p = 0.01) were predictors of complete response. In predicting complete response, sigmoidoscopy was more sensitive (76.0% vs 62.5%) and specific (72.5% vs 69.2%) than MRI. The specificity further increased when 2 techniques were combined (82.5%). Retrospective study. The complete response rate after total neoadjuvant therapy was 37%. Low rectal tumors and the absence of extramural vascular invasion were predictors of complete response. Sigmoidoscopy was better in predicting incomplete response, whereas combination (MRI and sigmoidoscopy) was better in predicting complete response. See Video Abstract. ANTECEDENTES:La terapia neoadyuvante total en el tratamiento del cáncer de recto en estadios II-III implica la administración de quimioterapia de inducción o de consolidación con quimio radiación antes de la cirugía. La terapia neoadyuvante total se asocia con una mayor tasa de respuesta completa, que se define como la proporción de pacientes que tuvieron una respuesta patológica completa después de la cirugía o una respuesta clínica completa sostenida al menos durante un año bajo vigilancia.OBJETIVO:Identificar los predictores de respuesta completa a la terapia neoadyuvante total y comparar diferentes herramientas de diagnóstico para predecir la respuesta completa.DISEÑO:Estudio de cohorte retrospectivo.LUGARES:Un único centro de atención terciaria.PACIENTES:Pacientes con cáncer de recto en estadio II-III diagnosticados entre enero de 2015 y diciembre de 2021.INTERVENCIÓN(S):Terapia neoadyuvante total.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de respuesta completa, predictores de respuesta completa, sensibilidad y especificidad de la sigmoidoscopia y la resonancia magnética para predecir la respuesta completa.RESULTADOS:Se incluyeron 119 pacientes [edad media 56 (±11,3) años, 47 (39,5%) mujeres, 100 (84%) cáncer de recto en estadio III]. La mediana del tamaño tumoral fue de 5,1 (4-6,5) cm, 63 (52,9%) fueron tumores rectales bajos. Veintiún (17,6%) pacientes tenían invasión vascular extramural (EMVI), 62 (52,1%) tenían CEA elevado al inicio del estudio. Ciento ocho (90,8%) pacientes recibieron quimioterapia de consolidación. Después de la TNT, 88 (73,9%) de 119 pacientes fueron intervenidos quirúrgicamente, de los cuales 20 (22,7%) tuvieron respuesta patológica completa. Treinta y un (26,1%) pacientes fueron sometidos a observación y espera, de los cuales 24 (77,4%) tuvieron una respuesta clínica completa sostenida. La tasa de respuesta completa general fue del 37%. Los tumores rectales bajos [OR 1,5 (IC 95% 1,03-2,4), p = 0,04] y la ausencia de EMVI [OR 2,2 (IC 95% 1,1-5,6), p = 0,01] fueron predictores de respuesta completa. Para predecir la respuesta completa, la sigmoidoscopia fue más sensible (76,0 % frente a 62,5 %) y específica (72,5 % frente a 69,2 %) que la resonancia magnética. La especificidad aumentó aún más cuando se combinaron dos técnicas (82,5%).LIMITACIONES:Estudio retrospectivo.CONCLUSIONES:La tasa de respuesta completa después de la terapia neoadyuvante total fue del 37%. Los tumores rectales bajos y la ausencia de EMVI fueron predictores de respuesta completa. La sigmoidoscopia fue mejor para predecir la respuesta incompleta, mientras que la combinación (MRI y sigmoidoscopia) fue mejor para predecir la respuesta completa. (Traducción-Dr Osvaldo Gauto ).

Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management

ObjectiveTo evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in...

Abstract PO3-15-02: TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY

Abstract Introduction: Breast cancer is one of the most prevalent in women in the world and has shown extensive changes in treatment in recent decades. More patients are undergoing neoadjuvant chemotherapy in order to achieve pathological complete response (CPR) and perform less aggressive surgeries. CPR increases overall and disease-free survival and the decrease in tumor size increases the chances of conservative surgery. We have numerous studies that propose to discover CPR markers. Predictive factors of response to chemotherapy are important for treatment planning and the P53 gene, apoptosis-inducing gene, plays a role in inducing response to chemotherapy drugs that act by inducing apoptosis. The presence of mutations and genetic polymorphisms act by modulating this response. Among these, the codon 72 polymorphism is one of the most studied, as its polymorphic variants Arg/Arg, Arg/Pro and Pro/Pro encode a p53 with different functioning at the cell level. So, individuals with different polymorphisms will have different apoptotic action and different response to chemotherapy treatments. Objectives: Based on this knowledge, the study sought to correlate the polymorphism variants at codon 72 with the complete pathological response to neoadjuvant chemotherapy. Casuistic and Methods: The study was carried out at an oncology center in the state of Sergipe, in northeastern Brazil. A total of 206 patients with breast cancer who underwent neoadjuvant chemotherapy and core needle biopsy of the breast at the beginning of treatment were included in the stud,in the period from 2019 to 2022. From these patients, oral swab samples were collected for PCR evaluation of the P53 polymorphism at codon 72. The polymorphisms were studied using the Sanger technique at the Sao Paulo School of Medicine of the Federal University of São Paulo (UNIFESP). Patients were prospectively evaluated after surgery to verify the surgical pathological response after chemotherapy. Pathologic response was assessed using the RECIST criteria. The study was evaluated and approved by the ethics and research committee of UNIFESP and all patients signed an informed consent form. Results: Of the 206, 18.4% met the exclusion criteria (did not undergo surgery, interrupted chemotherapy treatment, insufficient genetic material in the swab, loss of follow-up). Of the 168 patients analyzed, 44.6% were Arg/Arg, 17.3% Pro/Pro and 38.0% Arg/Pro. Complete pathological response (PCR) was obtained in 21.4% of the patients, 10.1% had progressive disease (PD), 13.7% had stable disease (SD) and 54.2% had partial pathological response (PPR). Of the patients who achieved RPC, 47.2% were Arg/Arg, 38.9% Arg/Pro and 13.9% Pro/Pro without statistical significance, among the variants of polymorphisms. The only predictor of CPR in multivariate regression was immunohistochemistry (p< 0.001). The only predictor of CPR in multivariate regression was immunohistochemistry (p< 0.001) Conclusion: The P53 polymorphism at codon 72 is not a predictor of complete pathological response, but the Arg/Pro and Pro/Pro polymorphisms increase the chances of stable disease after neoadjuvant chemotherapy. Citation Format: Jussane Vieira, Afonso Nazário, João Pesquero. TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-02.

Termination of trastuzumab in HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression

The purpose of the study was to assess the prognosis of HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression and investigate the predictors of complete response. HER2-positive metastatic breast cancer patients who received long-term trastuzumab were included in the study. Predictors of complete response were analyzed with binary regression analysis. The prognosis of patients who had their trastuzumab-based treatment terminated was assessed. Eighty patients were involved in the study. The patients were received with trastuzumab for a median of 62 months (12–191). A complete response was observed in 60 (75%) patients. The median duration to development of complete response was found as 14.8 months (2.4–55). In logistic regression analysis: using endocrine therapy with trastuzumab (p = 0.04), menopausal status (p = 0.03), and the number of metastatic sites (p = 0.01) were found to be statistically significant factors for a complete response. Trastuzumab-based therapy of fifteen patients was terminated, six (40%) patients continued to receive an aromatase inhibitor, and nine (60%) patients were followed up without treatment. After termination of trastuzumab, at a median follow-up of 32 months (11–66), recurrence was detected in two (13.3%) patients. We detected that menopausal status, the number of metastatic sites, and using endocrine therapy with trastuzumab were predictors of complete response in HER2-positive metastatic breast cancer patients who received long-term trastuzumab-based therapy. We observed that HER2-positive metastatic breast cancer patients may be completely cured with trastuzumab-based therapy. There are no defined criteria for termination of trastuzumab treatment in this selected patient group. It is necessary to confirm our data with multicenter studies involving a large number of patients.

Relative impact of diagnosis and clinical stage on response to electroconvulsive therapy: a retrospective cohort.

Electroconvulsive therapy (ECT) is commonly indicated for refractory psychiatric disorders. However, response comparison across diagnoses is scantly investigated. Here, we aimed to evaluate the relative impact of diagnosis and clinical staging as response predictors in a cross-diagnostic sample. We investigate, in a retrospective cohort of adult inpatients (N=287) who underwent at least six sessions of ECT, predictors of complete response (a clinical global impression of 1) to ECT. We use adjusted regression models to estimate the impact of clinical diagnosis and staging on complete response and dominance analysis to assess the relative importance of these predictors. Those with a depressive episode as a primary indication for treatment were more likely than all the other groups to have complete improvement, while those with psychosis were the least likely; clinical stage had a significant influence on outcome in all diagnoses. A diagnosis of psychosis stood as the strongest predictor of non-response. An indication of ECT for psychosis (mostly schizophrenia) had a dominant impact in our cohort, indicating a worse chance of response. We also demonstrate that clinical staging can aggregate information on response to electroconvulsive therapy that is independent of clinical diagnosis.

Reduction of Tumor Length by >50%, Post Neoadjuvant Chemoradiation as a Predictor for Complete Response and Organ Preservation in Rectal Cancer

<h3>Purpose/Objective(s)</h3> 20-30% of the locally advanced rectal cancer patients undergoing neoadjuvant chemoradiation (NACRT) have complete response (CR) and are suitable for wait and watch approach. This tumor response can be enhanced by radiotherapy dose escalation such as brachytherapy which is typically given at the end of NACRT. However, there is no data so as to which patients are likely to benefit by brachytherapy to achieve CR. We aimed to identify decrease in tumor length following CTRT, as predictor of CR, and eventual organ preservation. <h3>Materials/Methods</h3> Patients diagnosed with T2-T4, N0-N2 distal rectal cancer treated from December 2017 to March 2021 were retrospectively reviewed. All were treated with radiation dose of 50 Gray (Gy) in 25 fractions (#) with concurrent capecitabine. All patients received escalated dose of radiation by high dose rate endorectal brachytherapy of 8-12 Gy in 2-3 #s within 2 to 3 weeks post CTRT. Baseline tumor length (MRI) and residual tumor length after CTRT during brachytherapy (assessed with planning MRI) were compared for response. Statistical analysis was done to determine decrease in tumor length as predictor of CR. <h3>Results</h3> One hundred patients records were reviewed. Disease and treatment characteristics are provided in table 1. Median length of tumor at baseline was 4.9 cm (3.8-6 cm). 39 patients had >50% decrement in tumor length (median length 3 cm) from baseline post CTRT, whereas 61 patients had <50% response. Out of 39 patients with>50% response, 26 patients achieved CR (66.7%) while 13 patients had partial or no response (33.3%), while out of 61 patients with <50% decrease in tumor length, 27 achieved CR (44.2%) and 34 had partial or no response (55.8%). The patients who had >50% reduction in tumor length had higher probability of achieving CR than the patients with <50% reduction (66% vs 44% p=0.029). <h3>Conclusion</h3> Response assessment at the end of CTRT with respect to decrease in length of tumor may predict CR and thus can lead to better selection of patients for escalated radiation dose via endorectal brachytherapy leading to higher rate of organ preservation.

Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer.

Simple SummaryThere are differences and similarities when assessing the short-term therapeutic response of chemotherapy and chemotherapy plus immunotherapy using imaging techniques, which may be necessary to make treatment decisions in malignant head and neck tumors. After both chemo- and immunochemotherapy, remission becomes measurable in cross-sectional and metabolic diagnostics after only one cycle of therapy, with 18FDG-PET/CT predicting complete remission of tumor cells in a representative biopsy better than MRI/CT examination in both therapeutic modalities. While complete tumor remission is highly likely (88%) after immunochemotherapy in tumors with low residual activity (≤40% of initial SUV), this is less common after chemotherapy alone (65%). In metabolic nonresponse with more than 80% residual activity, the probability of complete remission nevertheless is low after chemotherapy alone (6%). After immunochemotherapy, these false nonresponders are common (35%), requiring additional diagnostics by deep biopsy. Cases of pseudoprogression with an increase of SUVmax of more than 125% of the baseline were not observed.Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.

Early efficacy prediction of nasopharyngeal carcinoma based on 3D-ADC value acquired during radiotherapy: A phase II prospective study.

e18018 Background: Concurrent chemoradiotherapy (CCRT) is the main treatment for locally advanced nasopharyngeal carcinoma (LANPC). The prognosis of the patients with the same stage receiving the same treatment varies greatly. We aimed to investigate the dynamic changes of apparent diffusion coefficient (ADC) map from diffusion weighted MRI (DWI) of primary tumor (PT) and metastatic lymph nodes (LN) for NPC patients during RT process, and analyzed the potential correlations with volume reduction and objective response rate (ORR). Methods: A total of 50 NPC patients treated with CCRT were enrolled in this prospective study. All patients received a planned total dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The CCRT protocol was cisplatin (80-100mg/m2) every 3 weeks for 3 cycles. All patients received DWI scan at pre-RT, the 5th and 15th fractions and immediately post-RT on a 3.0T MRI system (b=0, 500, 800s/mm2) system. The ADC values of PT and LN were acquired on ADC map. RECIST1.1criteria was used to evaluate the ORR for both PT and LN. Clinical predictors of complete response (CR) were evaluated using log-rank test. Multivariate analyses were calculated using the logistic regression model. Receiver-operating characteristic (ROC) curve was used to determine the cut-off value of ADC value. P &lt;0.05. Results: After the completion of C CRT, the ORR of the PT was 100% (CR 75%, PR 25%), and that of the LN also reached 100% (CR 52%, PR 48%). Mean ADC increases and volume reductions in PT and LN were observed during RT. In the first stage (from pre-RT to the 5th fraction), the mean ADC increased significantly by 20.78% (PT), 22.96% (LN), while the volumes of PT and LN had minimal changes (PT:18.42cm3vs 16.72cm3, LN: 4.67cm3 vs 4.12cm3). In the second stage (from the 5th fraction to post-RT), the mean ADC increased by 45.58% (PT), 41.2% (LN), the volumes decreased by 86.07% (PT), 61.6% (LN). The increased mean ADC at the first stage had a positive correlation with the volume reduction after RT (r PT=0.32; r LN=0.40). Univariate analysis showed significant differences in the age, the changes of 3D-ADC at the 5th RT and the volume of PT and LN before RT (VPT, VLN) between CR group and PR group(p&lt;0.05), The binary logistic regression analysis demonstrated the ADC changes and the VPT, VLN were predictor of PT and LN efficacy evaluation. ROC analysis suggested the ADC changes had the better performance for PT and LN efficacy evaluation. The cut-off the ADC value changes of PT and LN was 193.52mm2/s (AUC = 0.750, p = 0.008) , 173.80mm2/s (AUC = 0.822, p &lt; 0.001) respectively. Conclusions: 3D-ADC values of PT and LN increased dramatically during RT for NPC patients. The 3D-ADC value of PT and LN was an independent prognostic factor for NPC patients. Early ADC changes at the 5th fraction might be a new and sensitive biomarker to predict the efficacy for NPC patients.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma: Virtual Tumor Absorbed Dose as a Predictor of Complete Response.

To evaluate the impact of virtual tumor absorbed dose (vTAD) on tumor response in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization. The institutional review board approved this retrospective single center study, which comprised 100 patients with nodular HCC who underwent yttrium-90 radioembolization between November 2015 and December 2019. The vTAD was calculated assuming that all infused microspheres were distributed only in the tumor. The ability of mean absorbed dose (mAD) and vTAD in predicting complete response were evaluated by receiver operating characteristic (ROC) curve analyses. The mAD was 263.9 Gy ± 125.8, and the mean vTAD was 2005.8 Gy ± 2348.9. In terms of tumor response, 63 patients had complete response, 25 partial response, and 12 stable disease. For predicting complete response, ROC curve analyses revealed that the area under the curve (AUC) value of the vTAD was significantly higher (p<0.001) than that of the mAD. Multivariate analysis revealed that Child-Pugh class A5, unilobar disease, and vTAD (>952 Gy) were significant factors in predicting complete response. High vTAD (>952 Gy) plays a significant role in complete response in patients with nodular HCC.

Predictors of Complete Response in Patients with Hepatocellular Carcinoma Treated with Trans-Arterial Radioembolization.

Background: Trans-arterial radioembolization (TARE) has shown promising results in treating hepatocellular carcinoma (HCC). We identified independent predictors of radiological complete response (CR) in patients with intrahepatic HCC who were treated with TARE. Methods: Patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited. CR was defined according to the modified Response Evaluation Criteria in Solid Tumors. Cox regression analysis was used to determine independent predictors of CR. Results: The median age of study participants (83 men and 19 women) was 64.3 years. The mean survival after TARE was 55.5 months, and 21 (20.6%) patients died during the study period. Patients who achieved CR (14 patients, 13.7%) had significantly higher serum albumin level (median 4.1 vs. 3.9 g/dL), lower total bilirubin level (median 0.6 vs. 0.7 mg/dL), lower aspartate aminotransferase level (median 30.0 vs. 43.0 IU/L), lower alkaline phosphatase level (median 79.0 vs. 103.0 IU/L), lower alpha-fetoprotein level (median 12.7 vs. 39.9 ng/mL), lower des-gamma-carboxyprothrombin level (median 575.5 vs. 2772.0 mAU/mL), lower model for end-stage liver disease (MELD) score (median 6.0 vs. 7.0), and smaller maximal tumor diameter (median 6.3 vs. 9.0 cm) compared to those who did not achieve CR (all p < 0.005). Multivariate Cox regression analysis showed that lower MELD score (hazard ratio (HR) = 0.436, p = 0.015) and maximal tumor size < 9 cm (HR = 11.180, p = 0.020) were independent predictors of an increased probability of radiological CR after TARE. Conclusions: Low MELD score and small maximal tumor size were independently associated with an increased probability of CR after TARE in patients with intrahepatic HCC.

Abstract PS10-44: Termination of trastuzumab-based treatment after complete response in HER2-positive metastatic breast cancer

Abstract Background: Trastuzumab has been used for HER2 positive breast cancer treatment for more than 20 years. The ratio of HER2 overexpression in breast cancer patients is about 20%. In this study, we aim to evaluate the prognosis of HER2 positive breast cancer patients with long term received trastuzumab and examined the predictors of complete response. Method: In this study, we included the patients with HER2 positive metastatic breast cancer received long-term trastuzumab. Demographic, clinical, pathological, and treatment data of the patients retrospectively recorded. Response rates of trastuzumab-based treatment evaluated by RECIST. The prognosis of the patients and predictors of complete response assessed with Kaplan-Meier analysis and logistic regression analysis, respectively. Also, the prognosis of the patients whose trastuzumab-based treatment was terminated was evaluated. Results: Median follow-up was 123.3 months (range, 32.2-330.3). Eighty patients included the study, and the median age of the patients was 43 (22-68). The patients received trastuzumab-based treatment with a median of 62 months (range, 12-191). The number of de-novo metastatic patients was 27 (33.8%). All patients had a pathological HER2 overexpressed tumor that scored 3+ (71.3%) by ımmunohistochemistry (IHC) or scored 2+ (28.7%) by IHC confirmed with FISH. In all patients, five-, ten-, and, fifteen – years overall survival were 96.1%, 86.8%, and 60.5%, respectively. A complete response was detected at 60 (75%) of the patients. The median time to complete response was 14.4 months (range, 2.4-47.8). In logistic-regression analysis: age at diagnosis (p=0.543), menopausal status (p=0.074), bisphosphonates treatment (p=0.682), palliative radiotherapy (p=0.935), and de-novo metastatic disease (p=0.405) were not statistically significant predictors for complete response. However, the number of metastatic sites (p=0.016), and the use of endocrine therapy (p=0.019) with trastuzumab were statistically significant. During the study period, trastuzumab-based treatment of twelve patients was terminated, four (33.3%) patients continue to receive aromatase inhibitör, and eight (66.7%) patients received no treatment. After termination of trastuzumab, at a median follow-up 44.7 months (range, 11.6-66.6), recurrence was not detected in the patients. Conclusions: In this study, we found that trastuzumab-based therapy can provide full recovery of HER2 positive metastatic breast cancer. For the patients with a long-term complete response, discontinuation of trastuzumab-based treatment should be considered. Also, hormone-positive patients should continue to receive aromatase inhibitör. The use of endocrine therapy with trastuzumab and the number of metastatic sites are predictors of the complete response Citation Format: Izzet Dogan, Esra Aydın, Nijat Khanmammadov, Adnan Aydıner, Pınar Saip. Termination of trastuzumab-based treatment after complete response in HER2-positive metastatic breast cancer [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 PS10-44.

Omalizumab in Chronic Inducible Urticaria: a Real-Life Study of Efficacy, Safety, Predictors of Treatment Outcome, Time to Response and Relapse

Clinical trials have shown the efficacy of omalizumab in some forms of chronic inducible urticaria (CIndU), but real-life evidence is limited. Specifically, little is known about the long-term efficacy and safety of omalizumab in the treatment of patients with CIndU, and predictors of complete response and time to response remain unknown.

Live births and maintenance with levonorgestrel IUD improve disease-free survival after fertility-sparing treatment of atypical hyperplasia and early endometrial cancer

ObjectiveOur objectives were to (1) compare different regimens of hormonal therapy (HT) in young women with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC), (2) assess reproductive and oncologic outcomes and (3) explore possible predictors of complete response (CR) and disease free survival (DFS). MethodsReproductive age women with AEH and Grade 1–2 endometrioid EC with no or minimal myometrial invasion on MRI treated with different regimens of HT were prospectively analyzed. Treatment protocols included levonorgestrel intrauterine device (LNG IUD), gonadotropin-releasing hormone agonist (aGnRH) or high-dose oral medroxyprogesteron acetate (MPA) separately and in combinations. ResultsTotal of 418 patients with AEH (n = 228) and EC (n = 190) aged 19–46 years received HT. Overall CR rate was 96% in AEH and 88% in EC patients (р < 0.001). None of the regimens used in AEH (LNG IUD + 2 D&C vs. LNG IUD + aGnRH vs. LNG IUD + 3 D&C) was found inferior to the others (CR of 98%, 95%, 100%, respectively, p > 0.05) except for MPA alone (CR 87%, р = 0.009). Out of four HT regimens used in EC LNG IUD + aGnRH+3 D&C was superior to all others (CR 96%, р = 0.026) where 2 D&Cs were performed or oral MPA was prescribed. The median follow-up for 339 patients was 33 months (range: 3–136), 68% of patients (n = 232) attempted conception, 38% (n = 89) of them used ART. The birth rate was 42% (n = 97). The rate of recurrence was 26% (50/196) in AEH group and 36% (51/143) in EC group (p = 0.05). Birth after treatment (HR = 0.24) or LNG IUD maintenance (HR = 0.18) were associated with superior DFS (p < 0.001 for both). ART use did not influence DFS. ConclusionHormonal therapy of AEH and early EC with LNG IUD is superior to MPA-containing regimens, however still carries high risk of recurrence. Post-treatment pregnancy rates are satisfactory and can be further improved by broader ART use which was proven safe. Initial diagnosis of AEH, post-treatment child birth and LNG IUD maintenance were associated with decreased rates of recurrence.

Elevated level of peripheral blood T lymphocytes are predictors of complete response to chemoradiotherapy in patients with locally advanced rectal cancer

Elevated level of peripheral blood T lymphocytes are predictors of complete response to chemoradiotherapy in patients with locally advanced rectal cancer

Combined mepacrine-hydroxychloroquine treatment in patients with systemic lupus erythematosus and refractory cutaneous and articular activity.

Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such patients.

Can We Reliably Predict a Clinical Complete Response in Rectal Cancer? Current Trends and Future Strategies

Prediction of clinical complete response is pivotal in the management of patients with rectal cancer. The ability to determine tumor response to neoadjuvant therapy in rectal cancer might guide subsequent treatment modalities. We review the current literature on predictors of complete response after neoadjuvant for rectal cancer with an emphasis of clinical complete response rather than pathological complete response. Clinical and radiological findings have been used to predict response, as well as a myriad of biomarkers. There is limited evidence validating most of these strategies. The role of imaging in defining tumor response has been assessed retrospectively. The TRIGGER trial is a randomized trial that will evaluate stratified management of rectal cancer based on their tumor regression grade. The management of locally advanced rectal cancer is evolving. The ability to predict clinical complete response in patients that have undergone neoadjuvant chemoradiation will allow us to select potential patients that can benefit from a “watch and wait” strategy. Identifying patients that will have a complete response will result in decreased surgical overtreatment, favoring organ-sparing strategies. Treatment individualization will require further research. Emphasis should be made in validating prediction markers; these should be cost-effective and of minimally invasive retrieval. Surveillance protocols to assess for tumor regrowth are yet to be determined.

Synchronous Adie's syndrome and type 1 antineuronal nuclear antibody (anti-Hu)-related paraneoplastic neurological syndromes as predictors of complete response in limited-stage small-cell lung cancer: A case report.

Adie's syndrome (AS) and paraneoplastic sensorimotor neuropathy with cerebellar ataxia (PSN CA) are extremely rare, rapidly progressive, autoimmune diseases associated with the development of antibodies against neuronal-specific Hu proteins that are abnormally expressed in small-cell lung cancer (SCLC). We herein present the unique case of a 55-year-old obese woman, previous heavy smoker, who, during treatment with standard cisplatin-etoposide chemotherapy for limited-stage SCLC, developed simultaneous AS and worsening symptoms consistent with PSN CA that led to significant neurological disability and severe axonal electrophysiological pattern on nerve conduction studies. Serology confirmed the presence of low-titre type 1 antineuronal nuclear antibodies (ANNA-1), previously referred to as anti-Hu antibodies. Following plasmapheresis, immunosuppressive therapy and physical rehabilitation, the neurological symptoms progressively improved. The tumour completely regressed, with no recurrence detected on subsequent radiological examinations. The aim of this case was to highlight the importance of a multidisciplinary team approach for early recognition and rapid treatment of paraneoplastic neurological syndromes (PNS) as key to achieving significant recovery and marked improvement of the neurological deficit. This report extends the literature by confirming earlier studies showing that the presence of serum ANNA-1 in SCLC, an aggressive type of pulmonary carcinoma that is challenging to treat, may portend a more favourable prognosis and response to chemotherapy. Thus, patients with SCLC and new-onset neurological symptoms should be tested for ANNA-1. The role of a multimodality approach to treating PNS is also emphasized.

Elevated levels of peripheral blood T lymphocytes are predictors of complete response to chemoradiotherapy in patients with locally advanced rectal cancer

Elevated levels of peripheral blood T lymphocytes are predictors of complete response to chemoradiotherapy in patients with locally advanced rectal cancer

Measurement of Phosphorylated ERK As a Prognostic and Predictive Marker for MEK Inhibition in Pediatric B-Lymphoblastic Leukemia: A Pilot Study

Abstract Background: Outcomes for patients with relapsed B- acute lymphoblastic leukemia (B-ALL) remain suboptimal. We and others have identified the Mitogen activated protein kinase/ Extracellular signal regulated kinase (MAPK/ERK) pathway as a primary driver of drug resistance in pediatric B-ALL. Constitutive activation of ERK has been found to be an independent predictor of complete response and is associated with other poor prognostic factors in adults with B-ALL. Mutations that affect activation of the Ras/Raf/MEK/ERK pathway have been found in up to 40% of children with newly diagnosed and relapsed ALL and these mutations correlate with early relapse and poor overall survival. However, we have demonstrated MAPK activation in the absence of Ras pathway mutations, suggesting alternative mechanisms of activation. Hypothesis: We hypothesize that activation of the MAPK pathway drives drug resistance in pediatric B-ALL. Activation of this pathway at diagnosis may portend a high likelihood of relapse and inhibition of the MAPK pathway may restore chemosensitivity to conventional agents. Methods: For our initial pilot study, a total of 24 patient samples from initial diagnosis obtained from Children's Oncology Group cell bank and from NYU, were thawed and placed either in serum-free media or media containing Trametinib (MEK1/2 inhibitor) at 1µM for 4 hours. Samples were then stimulated with Phorbol 12-myristate 13-acetate (PMA), a specific activator of Protein Kinase C, which activates MEK via Ras. Samples were then fixed with 4% paraformaldehyde, permeabilized with 95% methanol, and stained for Caspase 3, CD10, phosphorylated ERK (p-ERK), and p-AKT. All samples were simultaneously processed on the BD LSRII HTS and analyzed on FlowJo software (Treestar, V.10). Viable leukemic blasts were identified as CD10 positive and Caspase 3 negative cells, which were gated on for further analysis. Median fluorescence intensity (MFI) for phosphorylated proteins was measured, expressed as a ratio to isotype controls and compared between samples. MAPK activation was defined by maximal p-ERK levels upon stimulation with PMA. Inhibition was quantified as percentage decrease in maximal p-ERK levels (upon PMA stimulation) after treatment with Trametinib. Targeted Sanger sequencing of commonly mutated exons of Ras pathway genes (NRAS, KRAS, FLT3 and PTPN11) was performed on 14 samples based on availability of DNA. Results: Of our 24 samples, 4 samples were excluded from analysis due to poor viability (&lt;40% live cells), giving an assay success rate of 83.3%. We were able to successfully measure p-ERK in all 20 viable patient samples and also measure levels of baseline p-AKT in 16 samples. A wide range of p-ERK levels and MAPK activation was observed within patient samples (median activation ratio 12.3, range 4.4-44.7) and 7 samples showed markedly higher levels of activation with ratios between 21.9 - 44.78. Levels of inhibition by Trametinib ranged from 0-82.2%, with a median of 43%. Greater degree of MAPK activation was found to correlate strongly with higher levels of inhibition by Trametinib (overall correlation coefficient 0.72). In 2 samples, the levels of inhibition by Trametinib seemed lower than anticipated for levels of MAPK activation, but both of these samples showed higher than average levels of p-AKT (p-AKT to isotype ratio of 12.3-12.9, median of 2.4 in rest of the samples), suggesting a possible alternative mechanism of activation via the PI3K/AKT signaling pathway. DNA was obtained for Sanger sequencing in 14 of the 20 viable patient samples. Three of the 14 samples had point mutations in Ras pathway genes of which two had mutations in exon 2 of NRAS while one had a mutation in exon 14 of FLT3. Two of the seven patient samples with the highest MAPK activation had Ras mutations, which is consistent with our prior data showing that additional mechanisms of pathway activation are operative. Conclusion: We have successfully established a phospho-flow protocol that enables the measurement of MAPK activation in real time in patient samples. Based on our pilot data, we also conclude that MAPK activation in itself serves as a better predictive marker for susceptibility to MAPK inhibition, as opposed to Ras pathway mutation status alone. Ongoing investigation will allow correlation with outcome and the assay could serve in the future to identify those patients who might benefit from MEK inhibition or other nodes in the pathway. Disclosures Loh: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding.

Predictors of Complete Response and Disease Recurrence Following Chemoradiation for Rectal Cancer.

Approximately 10-40% of rectal patients have a complete response (CR) to neoadjuvant chemoradiation (CRT), and these patients have improved survival. Thus, non-operative management ("watch-and-wait" approach) may be an option for select patients. We aimed to identify clinical predictors of CR following CRT. Patients treated with definitive CRT for T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal cancer from August 2004 to February 2015 were retrospectively reviewed. Most patients were treated with 50.4 Gy radiation and concurrent 5-fluoruracil or capecitabine. Patients were considered to have a CR if surgical pathology revealed ypT0N0M0 (operative management), or if they had no evidence of residual disease on clinical and radiographic assessment (non-operative management). Statistical analysis was carried out to determine predictors of CR and long-term outcomes. Complete records were available on 138 patients. The median follow-up was 24.5 months. Thirty-six patients (26.3%) achieved a CR; 30/123 operatively managed patients (24.5%) and 6/15 (40%) non-operatively managed patients. None of the 10 patients with mucinous adenocarcinoma achieved a CR. Carcinoembryonic antigen (CEA) ≥5 μg/L at diagnosis (OR 0.190, 95% CI 0.037-0.971, p = 0.046), tumor size ≥3 cm (OR 0.123, 95% CI 0.020-0.745, p = 0.023), distance of tumor from the anal verge ≥3 cm (OR 0.091, 95% CI 0.013-0.613, p = 0.014), clinically node-positive disease at diagnosis (OR 0.201, 95% CI 0.045-0.895, p = 0.035), and interval from CRT to surgery ≥8 weeks (OR 5.267, 95% CI 1.068-25.961, p = 0.041) were independent predictors of CR. The CR group had longer 3-year distant metastasis-free survival (DMFS) (93.7 vs. 63.7%, p = 0.016) and 3-year disease-free survival (DFS) (91.1 vs. 67.8%, p = 0.038). Three-year locoregional control (LRC) (96.6 vs. 81.3%, p = 0.103) and overall survival (97.2 vs. 87.5%, p = 0.125) were higher in the CR group but this did not achieve statistical significance. CR was not an independent predictor of LRC, DMFS, or DFS. CEA at diagnosis, tumor size, tumor distance from the anal verge, node positivity at diagnosis, and interval from CRT to surgery were predictors of CR. These clinical variables may offer insight into patient selection and timing of treatment response evaluation in the watch-and-wait approach.