Histological Response Rate Research Articles

Li-Fraumeni-associated osteosarcomas: The French experience.

Describe clinical characteristics and outcome of Li-Fraumeni syndrome (LFS)-associated osteosarcomas. TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) for patients of the same age group. Median age at first osteosarcoma diagnosis was 13.7years (range: 5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients less than 10years of age (23% vs. 9%), and when compared with osteosarcomas in patients less than 25years were characterized by an excess of axial (16% vs. 10%) and jaw sites (15% vs. 3%) and histology with predominant chondroblastic component and periosteal subtypes (17% vs. 1%). Metastases incidence (25%) was as expected in osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%, 95% confidence interval [CI]: 42.6-71.1) were as expected in unselected series of osteosarcomas, whereas the 5-year event-free survival was 36.5% [95% CI: 25.3-52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 43.4% [95% CI: 28.5-57.5]. In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype, and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up.

Clinical significance of the maximum standardized uptake value on positron emission tomography to predict treatment response and outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy.

The association between the reduction rate of the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) during neoadjuvant chemoradiotherapy (NACRT) and the prognosis in patients with locally advanced rectal cancer is unknown. We retrospectively analyzed 62 patients with locally advanced rectal cancer who underwent curative surgery after NACRT at Kobe University between 2008 and 2021. The SUVmax reduction rate was calculated from preoperative and postoperative PET scans, and its association with the prognosis was investigated. The cutoff value for SUVmax reduction rate was 61.5%. Twenty patients had an SUVmax reduction rate > 61.5% (SUV responder group) and 38 patients had an SUVmax reduction rate ≤ 61.5% (SUV nonresponder group). Regarding pathological outcomes, the rate of a good histological response was significantly higher in the SUV responder group than in the SUV nonresponder group (80.0% vs. 21.1%, p < 0.001). Both the overall (OS) and relapse-free survival (RFS) rates were significantly better in the SUV responder group than in the SUV nonresponder group (OS, p = 0.035; RFS, p = 0.019). In the SUV responder group, only 1 case of recurrence was observed, with a median follow-up period of 56months. The rate of SUVmax reduction during NACRT might predict the long-term prognosis of patients with locally advanced rectal cancer.

Feasibility study of focused ultrasound in the treatment of vulvar low-grade squamous intraepithelial lesions with persistent symptoms

Objective This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms. Methods This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy. Results A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period. Conclusion This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

Comparison of budesonide vehicles in inducing histologic remission in pediatric eosinophilic esophagitis.

Oral viscous budesonide (OVB) is a common medication used to treat eosinophilic esophagitis (EoE). It is typically mixed with Splenda to produce a slurry, but other delivery vehicles have been used in clinical practice. We aimed to evaluate outcomes of pediatric EoE patients treated with OVB using different drug delivery vehicles. We performed a retrospective chart review of pediatric EoE patients treated with OVB. The primary aim was to evaluate rates of histologic remission (defined by <15 eos/HPF in both mid and distal esophagus) after 6-12 weeks of OVB treatment for each delivery vehicle. Secondary aims were to evaluate histologic response and endoscopic response and remission of different delivery vehicles, and to compare the efficacy of different treatment regimens. A total of 111 patients were included in the study. Median treatment duration was 3.4 months. Overall rate of histologic remission with OVB was 52.6%. There was no difference in rates of histologic remission (p = 0.313) or response (p = 0.195 and p = 0.681 in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission and response among the different vehicle types (p = 0.853 and p = 0.727) or treatment regimens (p = 0.244 and p = 0.157). Patients who achieve histologic remission were more likely to be non-Hispanic Caucasian. Our findings suggest there is no difference in histologic and endoscopic outcomes with various delivery vehicles or combination therapy with OVB in the treatment of EoE. More palatable and cost-effective vehicles can be used to treat EoE.

Systematic review and meta-analysis: the efficacy and safety of radiofrequency ablation for early superficial esophageal squamous cell neoplasia

Background and AimEsophageal squamous cell neoplasia (ESCN) is predominant in Asia. Endoscopic mucosal resection and endoscopic submucosal dissection (ESD) have both been recommended worldwide, however the application of endoscopic radiofrequency ablation (RFA) for treatment of early superficial ESCN remains inconclusive. We conducted a meta-analysis to study the effectiveness of RFA for early superficial ESCN.MethodsThree major bibliographic databases were reviewed for the enrollment of case series and cohort trials prior to August 23, 2023. We included adults diagnosed with early superficial ESCN who had been receiving endoscopic RFA or ESD if the treatments were available. Our focus was on the 12-month histological complete response rate (CR) and 3-month histological CR, as well as the acute and late postoperative adverse events (AEs) rate during the at follow-up periods.ResultsNine studies were enrolled for qualitative synthesis of narrative review, with eight trials involving a total of 447 participants for analysis. The pooled 12-month and 3-month histological CR were 0.83 (95% CI, 0.59–0.94, I2 = 80%) and 0.74 (95% CI, 0.67–0.80, I2 = 0%), respectively. As for safety, the acute and late postoperative AEs were 0.11 (95% CI, 0.05–0.26, I2 = 68%) and 0.19 (95% CI, 0.14–0.26, I2 = 0%), respectively. In subgroup analysis, the incidence of bleeding, laceration and perforation after endoscopic RFA showed 0.06, 0.06 and 0.02, respectively. When compared with ESD, RFA showed lower acute AEs and late AEs without any obvious significance.ConclusionsFor early superficial ESCN, endoscopic RFA achieved both higher 12-month complete remission and late complication postoperatively when compared to 3-month histological CR and acute AEs separately, while the stricture was encountered most commonly. The choice between endoscopic RFA and ESD remains inconclusive.

Twice-Daily Proton Pump Inhibitor Induces Higher Remission Rate in Eosinophilic Esophagitis Than Once-Daily Regimen Regardless of Total Daily Dose.

The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.

Findings in magnetic resonance imaging for restaging locally advanced rectal cancer

PurposeWe aimed to assess the prognostic value of restaging magnetic resonance imaging (MRI) in rectal cancer after neoadjuvant therapy and compare long-course chemoradiotherapy (LC-CRT) to short-course radiotherapy with delayed surgery (SCRT-delay).MethodsThis retrospective study included 267 patients with locally advanced rectal cancer (LARC) operated on between January 2016 and April 2019, all of whom received either LC-CRT or SCRT-delay in the neoadjuvant setting. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS) based on radiological response assessed using the magnetic resonance tumor regression grade (mrTRG).ResultsIn the LC-CRT group, cumulative 1-, 3-, and 5-year OS rates were 94.8%, 86.4%, and 79.0%, while in the SCRT-delay group, they were 83.3%, 68.9%, and 68.9% (P = 0.017). For CSS in the LC-CRT group, cumulative rates were 96.9%, 90.3%, and 85.0%, and in the SCRT-delay group, they were 88.6%, 81.4%, and 81.4% (P = 0.222). There were no significant differences in total histological response rates or local recurrence rates between the treatment groups. The good and moderate response group (mrTRG 1–3) had significantly better cumulative 1-, 3-, and 5-year OS and CSS compared to the poorer response group (mrTRG 4–5) (P = 0.023 for OS and P = 0.048 for CSS).ConclusionUnfavorable MRI response is a sign of poor prognosis in LARC. SCRT-delay is comparable to LC-CRT concerning the oncological outcome.

A phase II study of perioperative capecitabine plus oxaliplatin (CapeOx) therapy for advanced gastric cancer with multiple lymph node metastases (OGSG 1701).

304 Background: Gastric cancer with paraaortic lymph node metastasis or bulky lymph node metastasis is difficult to undergo curative resection without preoperative chemotherapy. Even if curative resection can be performed, the prognosis is extremely poor. The purpose of this study was to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin combined chemotherapy (CapeOx) for such advanced gastric cancer with multiple lymph node metastases. Methods: In this phase II trial, eligibility criteria were as follows; histologically proven gastric carcinoma; HER2 negative or unknown; with paraaortic lymph node metastases (#16a2/16b1) &gt; 10 mm and/or bulky lymph node metastases located at celiac axis, common hepatic artery, splenic artery and/or upper mesenteric vein which make a huge bulk &gt; 3.0 cm and/or multiple large bulks &gt; 1.5 cm; without any other metastatic lesions; not a large (≥ 8 cm) type 3 or type 4 gastric cancer; and age between 20 and 80 years old. Treatment included three cycles of preoperative CapeOx (capecitabine; 2,000 mg/m2 for 14 days, oxaliplatin; 130 mg/m2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after radical gastrectomy. The primary endpoint was response rate according to the RECIST v1.0. The planned sample size was 30 patients calculated on the hypothesis that the expected response rate was 65% and the threshold was 50%, with one-sided alpha of 0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. The number of patients with compete response, partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1, and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of 50.1 - 80.7% ( p = 0.049). The curative resection rate was 93.3%. The protocol treatment completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for oxaliplatin on preoperative CapeOx, and 80.8% for capecitabine and 64.2% for oxaliplatin on postoperative CapeOx. The histological response rate (Grade ≥ 1b) was 66.7%. The adverse events of Grade ≥ 3 included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10% on preoperative CapeOx, and neutropenia in 23.8% and diarrhea in 9.5% on postoperative CapeOx. The final results of the survival analysis are yet to come. Conclusions: Perioperative CapeOx therapy for advanced gastric cancer with multiple lymph node metastasis showed favorable response rate, curative resection rate and acceptable adverse events, and was considered a promising treatment regimen. Clinical trial information: UMIN000028749 .

Second annual report from the ISSPP PIPAC database.

To monitor the results of PIPAC directed therapy based on data from the International Society for the Study of the Pleura and Peritoneum (ISSPP) PIPAC database. Analysis of data from patients entered between June 15th, 2020, and February 28th, 2023. Twelve centers reported 2,456 PIPAC procedures in 809 patients (median 2, range 1-18) with peritoneal metastasis (PM) from different primary tumors. Approximately 90 % had systemic chemotherapy prior to PIPAC. Twenty-eight percent were treated in prospective protocols. Overall non-access rate was 3.5 %. Concomitant surgical procedures were performed during PIPAC in 1.6 % of the patients. Median length of stay was 2days. A total of 95 surgical complications were recorded, but only 22 % of these were graded≥3b. Seventeen-hundred-and-three adverse events were noted, and 8 % were classified≥3. The rate of complete or major histological response (peritoneal regression grade score, PRGS≤2) increased between the first and the third PIPAC in the group of patients who were evaluated by PRGS, and a PRGS≤2 or a reduction of the mean PRGS of at least 1 between first and third PIPAC were observed in 80 %. Disease progression (50 %) or technical issues (19 %) were the most important reasons for stopping PIPAC treatment. Median overall survival from first PIPAC directed treatment varied from 10.7months (CI 8.7-12.5) in gastric cancer to 27.1months (16.4-50.5) in mesothelioma. The ISSPP PIPAC database provides substantial real-world data supporting the use of PIPAC directed therapy in patients with PM from different primary tumors.

Diagnostic and therapeutic profile of patients treated for breast cancer in a radiotherapy unit: case of Dalal Jamm Hospital, Senegal

Objective: Describe the epidemiological, diagnostic and therapeutic profile of breast cancer in Senegal. Patients and Methods: One hundred and sixty patients with histological confirmation of breast cancer, treated consecutively between June 2018 and December 2020, were retrospectively included. Predefined clinical data were extracted from medical records containing patient demographic information, medical history, diagnostic features, and different treatment types. Data were collected, entered and analyzed using SPSS version 23.0 software. Results: The median age of the participants was 48 years with extremes of 27 and 81 years. The average consultation time was 4 (± 2.6) months. Breast cancer was mainly discovered to clinical signs (91.3%). Screening mammography revealed only 5% of cases. The vast majority of patients had a tumor larger than 3 cm (78.2%). Molecular characterization by immunohistochemistry was studied in 87 patients (54.3%) with a predominance of the triple negative profile (36.8%). Neoadjuvant chemotherapy was performed in 111 patients (74%). One hundred and thirty-five patients (92.5%) had undergone a mastectomy with modified Patey type dissection and only 11 patients (7.5%) had conservative treatment. The histological complete response rate after neoadjuvant chemotherapy was 17.1%. The median time between surgery and radiotherapy was 6 months. All patients in the series received radiotherapy. It was adjuvant in 142 patients and exclusive for palliative purposes in 18 patients. It was moderately hypofractionated in 105 patients (65.6%); classic in 52 patients (32.5%). Acute toxicities of radiotherapy were mainly represented by grade 1 radiodermatitis (22.5%). Conclusion: The descriptive analysis of these results shows the young age of the patients, the late diagnosis of breast cancer in our context and a treatment which is essentially based on neo-adjuvant chemotherapy and radical mastectomy.

Effects of Mirikizumab on Histologic Resolution of Crohn's Disease in a Randomized Controlled Phase 2 Trial

Histologic evaluation of mucosal healing in Crohn's disease (CD) is an evolving treatment target. We evaluated histologic outcomes for mirikizumab efficacy and associations with endoscopic and 1-year outcomes. Biopsies from 1 ileal and 4 colonic segments were evaluated at Weeks 0, 12, and 52 from each 170 SERENITY participants. Criteria for the Weeks 12 and 52 histologic response (a) no epithelial neutrophils or epithelial damage, or (b) >50% decrease in either Robarts Histopathology Index or active Global Histologic Disease Activity Score and remission (no mucosal neutrophils and no epithelial damage) had to be met in all biopsies. Agreement was evaluated between histologic and endoscopic endpoints. Associations between 1-year outcomes and Week 12 histologic and endoscopic response were evaluated. At Week 12, 1000 mg mirikizumab resulted in greater rates of histologic response (66% vs 27%, P<0.001) and remission (26% vs 6%, P<0.01) than placebo. Rates were numerically similar at 1-year (mirikizumab pooled response: 46-69%, remission: 13-31%). Agreement between Week 12 histologic and endoscopic response was 69% (Cohen's Kappa coefficient (κ)=0.40) and remission was 83% (κ=0.38) in all pooled arms, including placebo. At 1-year, the percentage of participants who received any dose of mirikizumab and achieved endoscopic remission differed by their Week 12 response: histologic (20%), endoscopic (25%), combined histology-endoscopy (45%), or neither (4%) (.003). In a post-hoc analysis of phase 2 data, mirikizumab induced and sustained histologic response and remission in CD over 52 weeks. Early combined histologic-endoscopic response was associated with endoscopic remission after 1 year of treatment with mirikizumab (ClinicalTrials.gov NCT02891226.

Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis.

Differences in eosinophilic esophagitis (EoE) presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic response. Hispanic EoE patients were compared with non-Hispanics at baseline and before and after treatment. The same analyses were repeated for White vs non-Whites. Of 1,026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis and had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; P = 0.01), and odds of histologic response remained lower after controlling for potential confounders (adjusted odds ratio 0.40, 95% confidence intervals: 0.19-0.87). Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS.

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis

Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE. We conducted a retrospective cohort study of EoE patients prescribed dupilumab and who were treatment-refractory to standard modalities. Patient demographics, clinical characteristics, EoE history, and procedural data (including the histologically worst, predupilumab, and postdupilumab endoscopies) were extracted from medical records. Symptomatic, endoscopic, and histologic responses were assessed for the worst and predupilumab endoscopies compared with the postdupilumab endoscopy. We identified 46 patients with refractory fibrostenotic EoE who were treated with dupilumab. Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the predupilumab esophagogastroduodenoscopies. The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively, and the Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all). Although the proportion of strictures was stable, there was a significant increase in the predilation esophageal diameter (from 13.9 to 16.0 mm; P < .001). Global symptom improvement was reported in 91% (P < .001). In this population of severe, refractory, and fibrostenotic EoE patients, most achieved histologic, endoscopic, and symptom improvement with a median of 6 months of dupilumab, and esophageal stricture diameter improved. Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials.

Additional value of interleukin-6 level to predict histopathological features of hepatocellular carcinoma before liver transplantation

Background & AimsInflammatory biomarkers are increasingly used as outcome predictors in the field of oncology and liver transplantation for HCC, but no study has shown the prognostic value of IL6 after LT.The goal of this study was to evaluate the predictive value of IL-6 on histopathological features of HCC on explant, its predictive value on recurrence risk and its additional value to other scores and inflammatory markers at the time of transplantation. MethodsFrom 2009 to 2019, all adults transplanted with a first liver graft and diagnosed with HCC on the explant analysis were retrospectively included (n = 229). Only patients who had a pre-LT IL6 level determination were analysed in this study (n = 204). ResultsHigh IL-6 level at transplantation was associated with a significantly higher risk of vascular invasion (15% vs 6%; p = 0.023), microsatellitosis (11% vs 3%; p = 0.013), lower rate of histological response both in terms of complete response (2% vs 14%, p = 0.004) and of necrosis (p = 0.010).Patients with pre-LT IL-6 level > 15 ng/ml had a lower overall and cancer-specific survival (p = 0.013).Recurrence-free survival was lower in patients with IL-6 > 15 ng/ml with a 3-year recurrence-free survival of 88% versus 78% (p = 0.034). IL6 levels were significantly higher in patients with early recurrence compared to patients without (p = 0.002) or with late recurrence (p = 0.044). ConclusionsIL6 level at transplantation is an independent predictor of pejorative histological features of HCC and is associated to the risk of recurrence.

Phase II neoadjuvant trial of albumin-bound paclitaxel, trastuzumab and pertuzumab followed by anthracycline based regimens in patients with operable HER2 positive breast cancer (OMC-BC05).

e12594 Background: Anthracycline and Taxane have been widely used and studied in neoadjuvant setting for treatment of locally advanced breast cancer. Various regimens have explored the addition of newer agents to determine safety and efficacy, and pathological complete response(pCR) has been demonstrated to be associated with favorable overall survival in primary breast cancer. Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to Trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (Her2)-positive breast cancer. In addition, APHINITY trial showed that Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to Tastuzumab and chemotherapy. We conducted a clinical phase II neoadjuvant trial of nab-Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline Based Regimens in Patients with Operable Her2 Positive Breast Cancer. Methods: The study is designed to evaluate nab-paclitaxel, Trastuzumab and Pertuzumab followed by EC or AC or FEC as neoadjuvant therapy in patients with Her2 positive operable breast cancer. Patients are treated with neoadjuvant nab-paclitaxel(260 mg/m2 ), Trastuzumab and Pertuzumab followed by EC(Epirubicin 90 mg/m2 , Cyclophosphamide 600 mg/m2) or AC(Doxorubicin 60 mg/m2 , Cyclophosphamide 600 mg/m2) or FEC(Fluorouracil 500mg/m2, Epirubicin 100 mg/m2 , Cyclophosphamide 500 mg/m2 ) q21d x 4. Patients undergo surgery 4-6 weeks later from completing chemotherapy. The primary endpoint, pCR is defined as no evidence of invasive tumors in the final surgical sample both in the breast and axillary lymph nodes. Secondary endpoints include overall response rate, disease-free survival, rate of breast conserving surgery, histological response rate, rate of sensory neuropathy ant the safety of the treatment. Results: In 30 evaluable patients, the pCR rate was 50%; 6/19 (31.6%) in ER-positive and 9/11 (81.8%) in ER-negative, 1/7 (14.3%) in IHC 2+, FISH positive and 14/23 (60.9%) in IHC 3+ . Of the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; no patient required a dose reduction for nab-PTX because of peripheral neuropathy. Conclusions: Neoadjuvant treatment using albumin-bound Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline based regimens appears to be effective especially in pure HER2 type or IHC 3+ cases.

Topical instillation of BCG immunotherapy for biopsy-proven primary upper urinary tract carcinoma in situ: A single institution series and systematic review.

Primary upper tract carcinoma in situ (UTcis) is a rare disease whose diagnosis and natural history are poorly understood. Radical nephroureterectomy is the standard of care but in imperatives or selected cases, topical instillations of Bacillus Calmette-Guérin (BCG) may represent a good alternative. The aim of this study was to report the histologic response to BCG instillations for the treatment of biopsy-proven UTcis and to systematically assess the current evidence on topical BCG instillation for the treatment of UTcis. This is a retrospective analysis of patients with biopsy-proven UTcis treated with BCG instillation between 1995 and 2020 in an expert center. The initial diagnosis was performed by a standardized random biopsy scheme during ureterorenoscopy (URS) in patients with positive cytology but negative CT and bladder biopsies. BCG course consisted of 6 weekly instillation of 81 mg Immucyst (Sanofi Pasteur MSD AG, Baar, Switzerland). Administration techniques were single-J, double-J and nephrostomy tube. The primary outcome was the rate of complete histological response at the 3-month 2nd-look-URS. Kaplan-Meier analysis curves assessed recurrence- and progression-free survival. A total of 22 patients (23 renal units) were included. Twenty-one (91.3%) patients completed the planned 6-week instillation cycle. Only one major complication was recorded (renal tuberculosis). Twenty patients had a 3-month 2nd-look-URS, with a complete histological response achieved in 17/20 cases (85%). After a median time of follow-up of 40 months (30-62), 8/20 patients harbored disease recurrence, including 5 cases of disease progression (≥pT2). The main limitations are the retrospective and non-comparative design of the study. Our systematic review (CRD42022324876) identified 15 studies (289 renal units). UTcis suffers from the lack of a standardized definition, and considerable heterogeneity has been found in making the diagnosis and assessing the response to treatment. Our study is the first to propose a histological diagnosis of UTcis as well as a histological re-evaluation of the response to treatment. Topical instillations of BCG appear to be a promising alternative, avoiding radical treatment in the majority of cases.

Endoscopic and Histological Placebo Rates in Crohn's Disease Clinical Trials: A Systematic Review and Meta-analysis.

Precise estimates of placebo response rates help efficient clinical trial design. In this systematic review and meta-analysis, we assessed contemporary placebo endoscopic and histological response rates in Crohn's disease (CD) clinical trials. MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to April 2022 to identify placebo-controlled studies of pharmacological interventions for CD. Endoscopic response, remission, and mucosal healing rates for participants assigned to placebo in induction and maintenance studies were pooled using a random-effects model. Point estimates and associated 95% confidence intervals (CIs) were calculated. In total, 16 studies (11 induction, 3 maintenance, 2 induction and maintenance) that randomized 1646 participants to placebo were eligible. For induction trials, the pooled placebo endoscopic response, endoscopic remission, and mucosal healing rates in participants assigned to placebo were 13% (95% CI, 10-16; I2 = 14.1%; P = .14), 6% (95% CI, 3-11; I2 = 74.7%; P < .001), and 6% (95% CI, 4-9; I2 = 26.9%; P = .29), respectively. The pooled endoscopic remission rate in patients who were bio-naïve was 10% (95% CI, 4-23) compared with only 4% (95% CI, 3-7) in bio-experienced patients. For maintenance trials, the pooled endoscopic response, remission, and mucosal healing rates were 7% (95% CI, 1-31; I2 = 78.2%; P = .004), 11% (95% CI, 4-27; I2 = 70.8%; P = .06), and 7% (95% CI, 3-15; I2 = 29.7; P = .23), respectively. Only 3 trials assessed histological outcomes. Endoscopic placebo rates vary according to trial phase and prior biologic exposure. These contemporary data will serve to inform CD trial design, sample size calculation, and end point selection for future trials.

A180 PLACEBO RATES IN MICROSCOPIC COLITIS RANDOMIZED TRIALS: APPLICATIONS FOR FUTURE DRUG DEVELOPMENT USING A HISTORICAL CONTROL ARM

Abstract Background There remains a need to develop effective medical therapies for patients with microscopic colitis (MC) who do not respond, are intolerant, or relapse on budesonide. Conducting randomized trials in MC is logistically and ethically challenging: budesonide is highly effective, and therefore, some institutional review boards have not allowed trials that randomize MC patients to placebo. However, comparing an investigational drug to budesonide is statistically infeasible: powering a non-inferiority study against a budesonide comparator arm with 90% power for a 10% non-inferiority margin would require over 700 subjects, yet fewer than 400 patients have been randomized in all historical MC trials. Therefore, alternative trial designs should be explored in MC, including the use of a historical control arm. Purpose To conduct a systematic review and meta-analysis to determine the proportion of placebo responders in MC trials that will inform future trials using a historical placebo comparator, and evaluate factors associated with placebo response. Method EMBASE, MEDLINE, and CENTRAL were searched from inception to January 7, 2022, and supplemented with conference abstracts to identify randomized controlled trials (RCTs) using a placebo comparator in adult patients with confirmed MC (either lymphocytic, collagenous, or mixed populations but excluding incomplete MC). The proportion of clinical and histologic responders in the placebo arms were pooled using random-effect models, statistical heterogeneity was evaluated using the I2 method, and the Freeman-Tukey double arcsine transformation was used to compute 95% confidence intervals (CI) using the score statistic and exact binomial method. All analyses were conducted in Stata 17.0. Result(s) Twelve placebo controlled RCTs were included, evaluating a total of 391 patients (163 randomized to placebo). The pooled placebo clinical response rate was 24.4% [95% CI 12.4%, 38.4%] (Figure 1), with substantial heterogeneity (I2=60.8%, p&amp;lt;0.01). The pooled histologic response rate was 19.9% [95% CI: 5.3%, 39.0%], with substantial heterogeneity (I2=66.4%, p&amp;lt;0.01). Subgroup analysis demonstrated higher placebo responses in lymphocytic colitis (39.9% [95% CI: 23.9%, 56.7%]) compared to collagenous colitis (19.8% [95% CI: 5.9%, 37.8%]), but not by allowance of baseline anti-diarrheals. Leave-one-out meta-analysis showed a reduction in heterogeneity after removal of Miehlke et al. 2014 (placebo response 21.0% [95% CI: 11.5%, 32.1%], I2=28.6%, p=0.17). Image Conclusion(s) Approximately 1 in 4 patients in MC trials will respond clinically to placebo and 1 in 5 will demonstrate a histologic response, although with substantial heterogeneity. T his highlights the need for standardized outcome definitions in MC trials and can serve to inform a Bayesian prior estimate for future trials that may consider using a historical placebo comparator. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest P. Hamilton: None Declared, K. Buhler: None Declared, G. Kaplan Grant / Research support from: Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire, Consultant of: AbbVie, Janssen, Pfizer, Amgen, Takeda, and Gilead, C. Lu Consultant of: Abbvie, Janssen, Ferring, and Takeda, Speakers bureau of: Janssen and Abbvie, C. Seow Consultant of: Advisory Boards: Janssen, Abbvie, Takeda, Ferring, Shire, Pfizer, Sandoz, Pharmascience, Fresenius Kabi, Amgen, Speakers bureau of: Janssen, Abbvie, Takeda, Ferring, Shire, Pfizer, Pharmascience, K. Novak Grant / Research support from: AbbVie and Janssen, Consultant of: Advisory board fees from AbbVie, Janssen, Pfizer, Ferring, and Takeda, speaker’s fees from AbbVie, Janssen, and Pfizer, R. Panaccione Consultant of: Abbott, AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, UCB. Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, Speakers bureau of: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals, C. Ma Grant / Research support from: Ferring, Pfizer, Consultant of: AbbVie, Alimentiv, American College of Gastroenterology, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Sanofi/Regeneron, Takeda, Pendopharm, Pfizer, Roche, Speakers bureau of: : AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer

Meta-analysis: Placebo rates in microscopic colitis randomised trials and applications for future drug development using a historical control arm.

Effective medical therapies for patients with microscopic colitis (MC) who fail budesonide are lacking. However, conducting randomised controlled trials (RCTs) in MC has been challenging due to small sample sizes. Understanding placebo responses can help inform more efficient future trials. The aim of this study is to estimate clinical and histologic placebo response rates and to determine factors associated with placebo response in MC. EMBASE, MEDLINE, and CENTRAL were searched until 7 January 2022, to identify placebo-controlled RCTs in adult patients with MC. Clinical and histologic response in the placebo arms were pooled using random-effects models. Stratified analyses based on disease- and trial-level characteristics, leave-one-out meta-analysis, and cumulative meta-analysis were performed. Twelve RCTs enrolling a total of 391 patients (placebo n= 163) with MC were included. Pooled clinical and histologic placebo response rates were 24.4% (95% CI: 12.4%-38.4%), I2 = 60.8%, p < 0.01, and 19.9% (95% CI: 5.3%-39.0%), I2 = 66.4%, p= 0.01 (tests for heterogeneity), respectively. Clinical response to placebo was numerically higher in patients with lymphocytic compared to collagenous colitis (39.9% vs. 19.8%, p=0.08). Heterogeneity in clinical response to placebo was significantly reduced when the Miehlke 2014 RCT was excluded in the leave-one-out meta-analysis or when a more stringent secondary definition of response based on the Hjortswang criteria was applied. Approximately one-quarter of patients in MC trials respond to placebo, although with substantial heterogeneity, reflecting the need for standardised outcome definitions and study designs for MC. This analysis also serves to inform future MC trials that may consider incorporating an external, historical placebo control arm, rather than directly randomising patients to placebo.

S502 Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis

Introduction: Differences in EoE presentation or treatment response by ethnic or racial minority status remains understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-white race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. Methods: We conducted a retrospective cohort study of the UNC EoE Clinicopathologic database with subjects of any age with a new diagnosis of EoE. Ethnicity and race were recorded as documented in the chart. For the subset who had treatment with a tCS and a follow-up endoscopy/biopsy, we assessed histologic response (< 15 eosinophils/hpf), global symptom response, endoscopic response, EREFS, and an endoscopic severity score (ESS). Hispanic EoE patients were compared to non-Hispanics at baseline, and before and after treatment. The same analyses were repeated for white vs non-whites. Results: Of 1026 EoE patients with ethnicity data, 23 (2%) were Hispanic and most clinical features at presentation were similar to non-Hispanic EoE patients. Out of 466 patients who received tCS, 8 were Hispanic and had numerically higher eosinophil counts (47.0 vs 24.5; p=0.09) and numerically lower histologic response (38% vs 57%; p=0.27) post-treatment. When comparing EoE patients in terms of race, non-white patients (13%) had many differences in presentation: younger age at diagnosis, less insurance, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. On multivariate analyses, age, vomiting, and furrows remained independently associated with non-white race. Of 475 patients with race data treated with tCS, the 49 non-whites had a significantly lower histologic response rate (41% vs 59%; p=0.01) (Table). After controlling for age, insurance, symptom length prior to diagnosis, total steroid dose, and whether dilation was performed, non-whites were less than half as likely to have histologic response (aOR 0.42, 95%CI: 0.21-0.83). Conclusion: Only 2% of EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. While treatment response was lower, this assessment was limited by a small sample size. The non-white EoE group was larger (13%), and presentation was less dysphagia-specific. Non-white patients also had a lower histologic response to tCS which persisted after accounting for differences in presentation.