Predictive Factors Of Response Research Articles

Efficacy of paclitaxel-carboplatin with bevacizumab as a late-line therapy for patients with advanced nonsquamous non-small cell lung cancer: A platinum rechallenge.

There is no well-established late-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel-carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late-line therapy in a clinical setting. Thirty patients with nonsquamous NSCLC who received paclitaxel-carboplatin with bevacizumab therapy as a late-line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated. The median progression-free survival (PFS) was 6.3 (range, 4.9-6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2-17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported. With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel-carboplatin and bevacizumab, a late-line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option.

First-line maintenance therapy with niraparib in advanced platinum-sensitive ovarian cancer: two 'long responder' case reports and review of the current literature.

The standard of care for newly diagnosed advanced ovarian cancer is surgical cytoreduction plus platinum-based chemotherapy; however, recurrent disease frequently occurs after treatment. Poly(ADP-ribose) polymerase (PARP) inhibitors as first-line maintenance therapy have been demonstrated to significantly reduce the risk of disease progression or death in patients with advanced ovarian cancer who have a complete or partial response to first-line platinum-based chemotherapy. Niraparib is the only PARP inhibitor that offers a significant progression-free survival benefit compared with placebo in this patient population regardless of the homologous recombination status. However, predictive factors for treatment responses and approaches to dose optimization remain to be investigated. In this study, two Chinese patients with newly diagnosed advanced ovarian cancer exhibited long-term responses to niraparib treatment, and hematological toxicity was successfully managed by dose adjustment. The literature on clinical trials and real-world experience on the efficacy, tolerability, and dose individualization of niraparib treatment in Western and Chinese patients was also reviewed. Future research is warranted to identify the characteristics of 'long responders' to niraparib treatment.

Precision Medicine in Inflammatory Bowel Disease.

Ulcerative colitis and Crohn's disease are traditionally defined as the two main subtypes of inflammatory bowel disease. However, a more recent view considers IBD as a spectrum of heterogeneous phenotypes with consistent differences in clinical presentation and behaviors, likely explained by differences in underlying pathogenetic mechanisms. The etiology is still elusive, and the suggested pathogenesis is a complex interplay among genetic predisposition and abnormal immune response at the mucosal intestinal level, activated by only partially identified environmental triggers leading to altered intestinal permeability and impaired handling of gut microbiota. The undeniable continuous progress of medical therapy with more frequent shifts from traditional to more advanced modalities also underlines the actual unmet needs. We are using medications with completely different mechanisms of action, with a lack of predictive factors of outcomes and response and still an unsatisfactory rate of success. In addition, we are missing still valuable and accurate markers to predict disease progression and severity in order to avoid under- or over-treatment. In such a complex scenario, it is undoubtful that the application of artificial intelligence and machine learning algorithms may improve the management and pave the way for precision and eventually personalized medicine in these patients; however, there are still several challenges that will be the focus of this review.

Circulating miR-146a predicts glucocorticoid response in thyroid eye disease.

Thyroid eye disease (TED) is an immune-mediated disorder of the eye. Intravenous glucocorticoid (GC) is the first-line treatment for patients with active moderate-to-severe TED. However, the response rate is between 50% and 80%. There are still no simple and reliable markers of responsiveness to GC therapy. We aimed to explore the possible role of miR-146a and miR-21 as predictors of responsiveness to GC treatment in TED. We carried out a prospective longitudinal study on 30 consecutive adult patients with active moderate-to-severe TED and eligible for GC therapy. All patients received the standard GC treatment with methylprednisolone i.v. In cases of progressive worsening of Gorman Score for diplopia or with duction restriction <30° in at least two consecutive controls, patients also underwent orbital radiotherapy. Response to GC treatment was defined as a decrease of two or more points in the clinical activity score (CAS) or CAS <4/10 at 24 weeks. Circulating miRNAs were extracted from patients' serum and quantified by real-time PCR. Twenty-three (77%) patients responded to GC. Thyroid surgery, higher CAS, greater proptosis and higher pre-treatment circulating levels of miR-146a emerged as predictive factors of responsiveness to GC. A ROC analysis revealed that miR-146a could predict responsiveness to GC with a positive predictive value of 100%. This is the first study investigating the role of pre-treatment circulating miR-21 and miR-146a to predict responsiveness to GC in TED. miR-146a emerged as a simple, objective, new marker of GC sensitivity that could be used to avoid ineffective administration of GC therapy to TED patients.

Prospective validation of VEGF and eNOS polymorphisms as predictors of first-line bevacizumab efficacy in patients with metastatic colorectal cancer

Bevacizumab (Bev) plus chemotherapy is a standard first-line treatment in metastatic colorectal cancer (mCRC), however to date no predictive factors of response have been identified. Results of our previous analysis on patients enrolled in a randomized prospective phase III multicenter study (ITACa study) showed a predictive value of Vascular Endothelial Growth Factor (VEGF) polymorphism (VEGF + 936), a 27-nucleotide variable number tandem repeat (VNTR) of the endothelial nitric oxide synthase (eNOS) gene and eNOS + 894 polymorphism. mCRC patients, treated with Bev plus chemotherapy, were included in this prospective validation trial. eNOS + 894G > T was analyzed by Real time PCR, while the eNOS VNTR and VEGF + 936C > T were determined by standard PCR and direct sequencing analysis. These polymorphisms were assessed in relation to progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). These three polymorphisms were not predictive of PFS (p 0.91, 0.59 and 0.09, respectively), and OS (p 0.95, 0.32 and 0.46, respectively). Moreover, the haplotype analyses did not confirm what was found in our previous study; patients bearing a specific haplotype of eNOS had not significantly improved outcomes. This prospective study failed to validate the predictive impact of eNOS and VEGF polymorphisms for response to Bev plus first-line chemotherapy in mCRC patients.

Predictive Factors of Response to Immunotherapy in Lymphomas: A Multicentre Clinical Data Warehouse Study (PRONOSTIM).

Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT.

Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is associated with significant mortality, and suboptimal antifungal treatment response. We describe predictive factors for treatment response and survival. We retrospectively analysed clinical, serological and radiological parameters at baseline and following antifungal treatment in patients with CPA and correlated with clinical and radiological response and survival. Fifty-nine patients were included with a mean age of 61 years. Thirty (51%) had a diagnosis of COPD. On clinical assessment at 6 months, 21 (36%) had clinically improved, 20 (34%) were clinically stable and 15 (25%) had deteriorated. Radiological improvement was observed in 30 (53%), stability in 11 (19%) and deterioration in 16 (28%). Only a lower C-reactive protein (CRP) at baseline was associated with a favourable clinical-radiological response. On univariate analysis, lower CRP, higher albumin, lower Aspergillus IgG and use of inhaled steroids were associated with lower mortality. An overall favourable response at 6 months was associated with lower mortality. Inflammatory markers and Aspergillus IgG were predictors of mortality in CPA. This suggests that mortality in CPA is driven mainly by the chronic fungal infection itself rather than the underlying disease, therefore early optimised treatment of CPA may lead to improved outcomes.

Stereotactic body radiation therapy for the treatment of lymph node metastases: a retrospective mono-institutional study in a large cohort of patients.

Lymph node metastases (NMs) are a common site of tumor spread that can occur at different times of the disease. Stereotactic body radiation therapy (SBRT) can be a therapeutic option for the treatment of NMs in the setting of oligometastatic disease (OMD). The aim of this study was to evaluate as primary end points the local control (LC) and secondary end points the locoregional nodal control (LRNC), distant nodal control (DNC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), and concurrently to assess the predictive factors of response. This is a retrospective study that analyzes a group of patients treated with SBRT on NMs from different primary tumors, with a of maximum five metastasis. Treated lesions were divided into four groups: oligometastatics, oligorecurrents, oligoprogressives, and oligopersistents. From 2007 to 2021, 229 NMs were treated in 174 patients with different primary tumor. The schedule most represented was 30 Gy in five fractions. The LC was obtained in 90% of NMs treated by SBRT with rates at 1, 3, and 5 years of 93%, 86%, and 86%, respectively. The LRNC was reached in 84% of cases with rates at 1, 3, and 5 years of 88%, 83%, and 77%, respectively. The DNC was obtained in 87% of cases with rates at 1, 3, and 5 years of 92%, 82%, and 78%, respectively. The DMFS was obtained in 38% of cases with rates at 1, 3, and 5 years of 57%, 40%, and 30%, respectively. The rate of PFS were 44%, 23%, and 13% at 1, 3, and 5 years, respectively. The rates at 1, 3, and 5 years of OS were 78%, 48%, and 36%, respectively. SBRT is an option for the treatment of NMS, with high rates of LC, improving survival, and with a good safety and tolerance. Tumor volume, tumor burden, lesion site, and doses can be predictive factors of response; however, multi-institutional studies with a greater number of patients could be helpful to better select patients and understand the right integrations between ablative treatment and systemic therapies.

Predictive factors associated with differential pathologic response to neoadjuvant chemohormonal therapy in high-risk localized prostate cancer

To explore the clinical parameters and molecular biomarkers that can predict differential pathologic response to neoadjuvant chemohormonal therapy (NCHT) in prostate cancer (CaP).A total of 128 patients with primary high-risk localized CaP who had received NCHT followed by radical prostatectomy (RP) were included. Androgen receptor (AR), AR splice variant-7 (AR-V7) and Ki-67 staining were evaluated in prostate biopsy specimens by immunohistochemistry. The pathologic response to NCHT in whole mount RP specimens was measured based on the reduction degree of tumor volume and cellularity compared to the paired pretreatment needle biopsy, and divided into 5 tier grades (Grades 0-4). Patients with Grades 2 to 4 (the reduction degree more than 30%) were defined as having a favorable response. Logistic regression was performed to explore the predictive factors associated with a favorable pathologic response. The predictive accuracy was evaluated by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).Ninety-seven patients (75.78%) had a favorable response to NCHT. Logistic regression showed that the preoperative PSA level, low AR expression and high Ki-67 expression in biopsy specimens were associated with a favorable pathologic response (P < 0.05). Furthermore, the AUC of the preoperative PSA level, AR and Ki-67 were 0.625, 0.624 and 0.723, respectively. Subgroup analysis revealed that the rate of favorable pathologic response to NCHT was 88.5% in patients with ARlowKi-67high, which was higher than patients with ARlowKi-67low, ARhighKi-67low, and ARhighKi-67high (88.5% vs. 73.9%, 72.9%, and 70.9%, all P < 0.05).A lower preoperative PSA level was an independent predictive factor for a favorable pathologic response. Moreover, the expression status of AR and Ki-67 in biopsy specimens were associated with differential pathologic response to NCHT, and AR low/Ki-67 high was also associated with favorable response but warrants further evaluation in this patient subgroup and future trial clinical trial design.

Imaging biomarkers on Angio-CT for predicting the efficacy of transarterial chemoembolization in hepatocellular carcinoma.

This study aimed to evaluate whether the lipiodol deposition pattern on intraprocedural Angio-CT could predict tumor treatment response in hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (c-TACE). This retrospective study enrolled intermediated and advanced HCC nodules treated with c-TACE and Angio-CT from June 2021 to June 2022. The therapeutic efficacy was evaluated according to the mRECIST standards. First, Angio-CT was used to determine lipiodol deposition at the end of c-TACE, redefined as complete, partial-complete, and incomplete groups. Second, the mean CT value of lipiodol deposition and its association with therapeutic efficacy were calculated in the complete model. Finally, the relationship between imaging biomarkers and efficacy was evaluated. A total of 45 patients with 72 HCC nodules were enrolled with 28 nodules in the complete group, 31 nodules in the partial-complete group, and 13 nodules in the incomplete group. The complete response (CR) proportion was significantly higher in patients with good lipiodol deposition compared with patients with poor lipiodol deposition (P<0.0001). There was no significantly different CR rate between CT value ≥800 and <800 HU (P=0.119) in the complete group. Meanwhile, the non-CR rate in cases with hepatic vein development was significantly higher than that in cases with no hepatic vein development in the arterial phase (P<0.0001). Complete lipiodol deposition on Angio-CT during c-TACE was a predictive factor for therapeutic response to TACE. For HCC nodules with well-deposited lipiodol, hepatic vein development on Angio-CT in the arterial phase was strongly associated with poor efficacy of TACE.

Torque teno virus viral load predicts SARS‐CoV‐2 vaccine response in kidney transplant recipients

AbstractTransplant recipients display poor responses to SARS‐CoV‐2 mRNA vaccines. In this retrospective study, we investigate torque teno virus (TTV) viral load (VL), a ubiquitous virus reflecting global immune response levels, as a predictive factor of vaccine response in kidney transplant recipients (KTR). Four hundred and fifty‐nine KTR having received two SARS‐CoV‐2 mRNA vaccine doses were enrolled, and 241 of them subsequently received a third vaccine dose. Antireceptor‐binding domain (RBD) IgG response was assessed after each vaccine dose and TTV VL was measured in pre‐vaccine samples. Prevaccine TTV VL &gt; 6.2 log10 copies (cp)/mL was independently associated with nonresponse to two doses (odds ratio (OR) = 6.17, 95% confidence interval (CI95) = 2.42–15.78) as well as to three doses (OR = 3.62, 95% CI95 = 1.55–8.49). In nonresponders to the second dose, high TTV VL in prevaccine samples or measured before the third dose were equally predictive of lower seroconversion rates and antibody titers. High TTV VL before and during SARS‐CoV‐2 vaccination schedules are predictive of poor vaccine response in KTR. This biomarker should be further evaluated regarding other vaccine responses.

Predictors of poor response to oral propranolol in infantile hemangiomas

BackgroundPropranolol is the first-line treatment for infantile hemangiomas (IH). Cases of propranolol-resistant infantile hemangiomas are rarely reported. The purpose of our study was to investigate the predictive factors for poor response to propranolol. MethodsA prospective analytical study was conducted between January 2014 and January 2022 including all patients with IH who received oral propranolol therapy at a dose of 2–3 mg/kg/day maintained for at least 6 months. ResultsA total of 135 patients with IH were treated with oral propranolol. Poor response was reported in 18 (13.4%) of the patients: 72% were girls and 28% were boys. Overall, 84% of the IH were mixed, and hemangiomas were multiple in three cases (16%), nasal tip hemangiomas accounted for four cases (22%), and 15 patients (83%) had segmental hemangiomas. There was no significant association between the age or sex of the children and type of response to treatment (p > 0.05). No significant association was found between the type of hemangioma and the therapeutic outcome as well as the recurrence after treatment discontinuation (p > 0.05). Multivariate logistic regression analysis revealed that nasal tip hemangiomas, multiple hemangiomas, and segmental hemangiomas were at greater risk of poor response to beta-blockers (p < 0.05). ConclusionPoor response to propranolol therapy has rarely been reported in the literature. In our series, it was approximately 13.4%. To our knowledge, no previous publications have focused on the predictive factors of poor response to beta-blockers. However, the reported risk factors for recurrence are discontinuation of treatment before 12 months of age, mixed or deep type IH, and female gender. In our study, the predictive factors for poor response were multiple type IH, segmental type IH, and location on the nasal tip.

IMRT-VMAT in Locally Advanced Rectal Adenocarcinoma: An Observational Multicenter Prospectic Study on Total Neoadiuvant Radiotherapy According Rapido Trial

Background: The phase III multicenter randomized RAPIDO trial (Rectal Cancer And Preoperative Induction therapy followed by Dedicated Operation) has shown the advantege of Total Neoadjuvant treatment (TNT) with short course radiotherapy (RT). However, data on local control have not been confirmed at 5.6 years median follow-up in favor of the TNT arm because patients from the experimental (EXP) group received more often 3D-CRT (p=0.029). The primary end-point of this multicentric observational prospectic study is to assess the real life safety and efficacy of RAPIDO trial protocol using VMAT and IMRT treatment in all enrolled patients. Moreover FDG-PET and MRI images for predictive features compared with cancer phenotype (status of K-ras and EGFR) and study on tumor microenviroment response to short course RT will be also provided. Methods: Locally advanced rectal cancer patients undergoing TNT as defined in RAPIDO trial will be enrolled and prospectively included in this study. MRI and FDG-PET will be performed to staging and restaging the disease. The tumor microenviroment changes assessment with immunophenotype and soluble PDL1 and on EVCs will be done. For sample size calculation, using OR 0.5, 100 patients will be enrolled into two years. Kaplan -model and proportional Cox method will be adopoted for OS, DFS and predictive factors for local control. Conclusions: The results of this study will be useful to assess prospectively the safety and effectiveness of VMAT and IMRT in short course TNT assuming predictive factors for response through radiomics, metabolomics and immunological features. Trial Registration: COMITATO ETICO UNICO REGIONALE ( CEUR ) N.50/2022; San Carlo Hospital, Potenza, Italy.

P-590 Similar mean follitropin delta daily/total doses yield satisfactory ICSI outcomes in different subgroups of maternal age and body mass index: a “real-world” experience with Rekovelle®

Abstract Study question Can similar mean follitropin delta daily/total doses yield satisfactory ICSI outcomes in different subgroups of maternal age and body mass index (BMI)? Summary answer Similar mean follitropin delta daily/total doses yield satisfactory number of oocytes and maturity rates, and pregnancy rates in different subgroups of maternal age and BMI. What is known already Rekovelle® (follitropin delta) is a novel recombinant human FSH (rFSH) expressed from a host cell line of human fetal retinal origin (PER.C6®) and is the first commercially available rFSH product derived from human cell lines. Rekovelle® allows the individualization of the initial dose of gonadotropin using predictive response factors to COS, such as anti-müllerian hormone (AMH) levels and body weight. In clinical practice different approaches can be adopted to obtain the most satisfactory response to controlled ovarian stimulation (COS). The objective of this study was to describe data on “real-world” Rekovelle® administration, regarding the response to COS and ICSI outcomes. Study design, size, duration This non-interventional study based on secondary use of data included patients undergoing ICSI in a private university-affiliated IVF center from Jan/2018 to Dec/2021. Each patient or cycle had to meet the following inclusion criteria: pre-menopausal women, undergoing COS with Rekovelle® (16 ug) daily for ICSI; diagnosed with infertility, or with partners diagnosed with male infertility factors, eligible for ICSI using fresh sperm from partner ejaculation; presenting with both ovaries. Participants/materials, setting, methods Ovarian response to stimulation and ICSI outcomes were described for 362 ICSI cycles. The primary outcome measures were the numbers of retrieved oocytes and maturity rates, and the secondary outcome were the ongoing pregnancy rates per fresh and per fresh and/or frozen-thawed embryo transfer. The results obtained with the population enrolled in the ESTHER-1 trial (extern), and a population stimulated with follitropin alpha 300 IU (on site) were recorded (data not shown, to be presented). Main results and the role of chance The mean total dose of follitropin delta administered in subgroups of age and BMI were as follows: age ≤35 y-old 156µg, 36-39 y-old 158 µg, and ≥40 y-old 157µg, and BMI: &amp;lt;18.5 165µg, 18.5-24.9 156µg, 25.0-24.9 159µg, and ≥30 171µg. Patients in the Follitropin delta group showed acceptable outcomes in different age and BMI groups (Table1). Adequate embryo morphokinetic development and euploidy rates were also observed, suggesting that the modified protocol does not interfere with oocyte/embryo competences and embryo implantation potential. This was further corroborated by satisfactory cumulative pregnancy rates. Limitations, reasons for caution Given its descriptive nature, we have focused on the number and maturity stage of retrieved oocytes instead of clinical ICSI outcomes. The use of historical cohort groups is another drawback. Despite the eligibility criteria for inclusion in the analysis, potential differences in the baseline characteristics cannot be ruled out. Wider implications of the findings Patients in different subgroups of age and BMI stimulated with similar mean follitropin delta daily and total doses showed satisfactory number of retrieved oocytes and maturity rates, and cumulative pregnancy rates without increasing OHSS, providing a rationale for conducting clinical trials to confirm the benefits of using this modified protocol. Trial registration number N/A

Construction and Evaluation of Clinical Prediction Model for Immunotherapy-related Adverse Events and Clinical Benefit in Cancer Patients Receiving Immune Checkpoint Inhibitors Based on Serum Cytokine Levels.

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of cancer therapy. This study aimed to develop novel risk classifiers to predict the risk of immune-related adverse events (irAEs) and the probability of clinical benefits. Patients with cancer who received ICIs from the First Affiliated Hospital of Xi 'an Jiaotong University from November 2020 to October 2022 were recruited and followed up. Logistic regression analyses were performed to identify independent predictive factors for irAEs and clinical response. Two nomograms were developed to predict the irAEs and clinical responses of these individuals, with a receiver operating characteristic curve to assess their predictive ability. Decision curve analysis was performed to estimate the clinical utility of the nomogram. This study included 583 patients with cancer. Among them, 111 (19.0%) developed irAEs. Duration of treatment (DOT)>3 cycles, hepatic-metastases, IL2>2.225pg/mL, and IL8>7.39pg/mL were correlated with higher irAEs risk. A total of 347 patients were included in the final efficacy analysis, with an overall clinical benefit rate of 39.7%. DOT>3 cycles, nonhepatic-metastases, and irAEs and IL8>7.39pg/mL were independent predictive factors of clinical benefit. Ultimately, 2 nomograms were successfully established to predict the probability of irAEs and their clinical benefits. Ultimately, 2 nomograms were successfully established to predict the probability of irAEs and clinical benefits. The receiver operating characteristic curves yielded acceptable nomogram performance. Calibration curves and decision curve analysis supported the hypothesis that nomograms could provide more significant net clinical benefits to these patients. Specific baseline plasma cytokines were closely correlated with irAEs and clinical responses in these individuals.

Treatment outcomes of radium-223 in patients with metastatic castration-resistant prostate cancer: An experience before National Health Insurance reimbursement in Taiwan.

Radium-223 (Ra-223), an α-particle-emitting isotope, inhibits bony metastases and prevents patients from skeletal-related events in metastatic castration-resistant prostate cancer (mCRPC). We retrospectively reviewed the treatment response, predictive factors, and adverse events (AEs) of Ra-223 before the National Health Insurance reimbursement in a Taiwanese tertiary institute. Patients treated with Ra-223 before January 2019 were enrolled and categorized into progressive disease (PD) and clinical benefits (CB) groups. Laboratory data before and after the treatment were collected, and spider plots concerning percentage changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) were prepared and calculated statistically. CB/PD, baseline ALP, LDH, and PSA levels were also adopted as stratification factors for overall survival (OS). Among 19 patients included, 5 (26.3%) and 14 (73.4%) belonged to the PD and CB groups, respectively, with no significant difference observed in the baseline laboratory data. The percentage changes in ALP, LDH, and PSA levels after Ra-223 treatment were statistically significant among the two groups (ALP: CB 54.3 ± 21.4% vs PD 77.6 ± 11.8%, p = 0.044; LDH: CB 88.2 ± 22.8% vs PD 138.3 ± 49.0%, p = 0.046; PSA: CB 97.8 ± 61.7% vs PD 277.0 ± 101.1%, p = 0.002). The trends of LDH between the two groups in spider plot were separated significantly. There were no differences in the AEs between the two groups. CB had a longer median OS than the PD group (20.50 months vs 9.43 months, p = 0.009). Patients with LDH <250 U/L at baseline tended to have longer OS but without significance. The CB rate of Ra-223 was 73.7%. No predictive factor for treatment response was obtained from pretreatment data. The mean percentage changes in ALP, LDH, and PSA levels compared with baseline significantly differed between the CB and PD groups, especially the LDH levels. The CB and PD groups showed different OS, with LDH levels exhibiting the potential to predict OS.

Identification of Predictive Factors for Pathologic Complete Response in Rectal Cancer Patients Undergoing Neoadjuvant Treatment: A Retrospective Study.

Background: Colorectal cancer is a serious illness, with rectal cancer accounting for thirty percent of all cases. For patients diagnosed with rectal cancer, neoadjuvant downstaging chemoradiotherapy is often necessary due to advanced disease at presentation. However, for certain patients, neoadjuvant chemotherapy can result in a complete response, leading to the possibility of overtreatment during subsequent definitive surgery. Methods: In order to identify predictors for clinical or pathologic complete response, we conducted a retrospective study on 231 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant treatment. Results: Our results indicate that tumor characteristics remain the primary predictive factors for treatment response in rectal cancer patients. Specifically, we found that a complete pathologic response was more likely in patients with stage I/II disease compared to stage III/IV. However, we did not identify any statistically significant associations between radiotherapy characteristics (such as fractionation, treatment technique or total dose) and complete response rates. Conclusions: In conclusion, our study highlights the importance of tumor stage in predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer patients. Other clinical and pathologic factors, such as tumor size, may also be important predictors of treatment response and should be explored in future studies.

Efficacy of immunotherapy in MSI metastatic colorectal cancer patients: A Real-World Italian multicentric retrospective study (Colon-MSI Study).

e15595 Background: The treatment with Immune checkpoint inhibitors (ICIs) is the gold standard therapy in metastatic colorectal cancer (mCRC) patients (pts) with microsatellite instability (MSI). The aim of the study was to describe a cohort of MSI mCRC pts treated with ICIs, before pembrolizumab approval, to evaluate efficacy and toxicity in a real-world setting and to identify possible predictive factors of response. Methods: We retrospectively collected data of pts with MSI mCRC treated with ICIs (anti-PD1 or anti-CTLA-4 antibodies, or in combination) before June 30, 2021, in 14 Italian Cancer Centers. The OS was calculated from the diagnosis of metastatic disease, and the PFS from the beginning of ICIs. Survival analyses were stratified between treatment naïve and pre-treated pts. We explored the correlation between clinicopathological factors and refractory pts who underwent progression disease (PD) within 3 months from the start of ICI. Results: In this preliminary analysis, we reported 60 consecutive pts with data available. Among all, 30 (50%) were male, 37 (62%) with ECOG PS 0-1; 21 (35%) were at stage IV, and 37 (62%) had right colon tumor site. The most common metastatic sites were lymph nodes, liver, and peritoneum, and 34 (57%) pts had a single metastatic site. 23 (38%) pts had a mucinous adenocarcinoma, and 20 (33%) were BRAF mutated. Nivolumab, Pembrolizumab, and Ipilimumab plus Nivolumab were administered in 24 (40%), 34 (57%), and 2 (3%) pts, respectively, and as first-line therapy in 13 (22%) pts. The median duration of treatment was 22 months (0-43), with 21 pts still ongoing. 13 (22%) pts were refractory to ICIs, and only 4 (7%) pts discontinued treatment for G3-G4 adverse events. The OS, PFS and DCR were different between treatment naïve and pre-treated pts with a positive trend (not statistically significant) toward untreated pts (Table 1). Male gender (p = 0.03), stage IV (p = 0.04), and ≥ 2 metastatic sites (p = 0.01) were significantly associated with refractory ICIs pts, but none of these factors was correlated with poor outcomes in multivariate analysis. Conclusions: Our preliminary data confirm that immunotherapy is an effective and well-tolerated treatment in MSI mCRC pts, with long-term clinical outcomes reported. These results suggest better outcomes when ICIs are administered in the first-line setting. Further analysis will be provided after the completion of the accrual. [Table: see text]

Impact of SPARC expression on pembrolizumab treatment response and prognostic role in advanced stage non-small cell lung cancer.

e21042 Background: Secreted protein acidic and cysteine-rich (SPARC) was highly expressed in non-small cell lung cancer (NSCLC) tissue. Studies have indicated the association between SPARC expression and immune-cell infiltration and the prognosis of lung cancer. Despite the optimal first-line treatment approach in advanced NSCLC that lacks a driver mutation includes immunotherapy with or without chemotherapy, a well-defined tool or test for predicting response has yet to be created. We aimed to elucidate the influence of SPARC expression terms of clinicopathology, pembrolizumab response and prognosis in metastatic NSCLC patients. Methods: Thirty-six patients diagnosed with advanced-stage NSCLC without actionable driver mutation and recieved pembrolizumab in the first line setting were included in this study. Programmed death ligand-1(PD-L1) and SPARC expression were assessed by means of PD-L1 IHC 22C3 pharmDx and BenchMark ULTRA assay(Ventana Medical Systems, Tucson, AZ) in paraffin-embedded blocks. The expressions were categorised according to the tumor proportion score. Staining intensity of SPARC was graded according to the following criteria: 1+ (weak), 2+ (moderate), and 3+(strong). Results:The median age was 62 (range 45-81). One patient was female, and four patients did not have a smoking history.Twenty-seven of tumor were adenocarcinoma, and six were squamous cell carcinoma. PDL-1 status was &lt; 1% in 4 (11.4%), 1-49% in 12 (34.3%), and &gt; 50% in 20 (54.3%) patients.There was no significant correlation between SPARC expression and smoking status, histologic type of tumour, T and N status, and liver and bone metastasis. Central nervous system (CNS) metastasis and progression was seen in 8 (57.1%), 2 (12.5%), and 1 (16.7%) and in 6 (16.7%), 0, and 6 (37.5%) patients with SPARC 1+,2+, and 3 +, respectively. Controversially, higher SPARC expression was significantly correlated with lower rates of brain metastasis but higher rates of CNS progression (p = 0.022 and p = 0.011, respectively). While PD-L1 and SPARC expression were not significantly correlated, a trend toward low SPARC expression was seen in patients with PD-L1 &gt; 50%. The objective response rate (ORR) trended to be higher in the SPARC 1+ group (85.7%, 43.8%, and 50.0% in SPARC 1+, 2+ and 3+ group, respectively, p = 0.052). Univariate analysis revealed that SPARC expression was not a significant prognostic factor for both PFS (p = 0.7) and OS (p = 0.07). But, low SPARC expression was a significant predictive factor for the first-line pembrolizumab treatment response (p = 0.04, OR:0.11, 95%CI 0.01-0.92) in NSLC patients. Conclusions: Our study lightened a new area in the literature that SPARC expression might predict the pembrolizumab response and might be a marker for CNS progression in NSLC patients. These results should be explored in further studies to address the potential therapeutic implications of SPARC expression.

Analyzing Predictive Factors for Pathologic Complete Response for Locally Advanced Rectal Cancer

Analyzing Predictive Factors for Pathologic Complete Response for Locally Advanced Rectal Cancer