Pathological Complete Remission Research Articles

Efficacy of sintilimab combined with neoadjuvant chemotherapy and trastuzumab in conversional treatment of locally advanced HER2-positive gastric cancer: case analysis and literature review

BackgroundRegional lymph nodes that are fixed and fused into clusters or those exhibiting metastases outside the regional lymph nodes are generally classified as stage IV (M1) or unresectable. Patients with such nodes almost always need pre-operative treatment so that they can undergo surgical resection. Combining immunotherapy with trastuzumab and chemotherapy significantly improved the prognosis of HER-2 positive gastric/gastroesophageal junction (G/GEJ) cancer. However, very few reports are available on the role of immunotherapy in converting patients with unresectable cancer to resectable cancer.MethodsIn this study, we report on four patients with GC who were preoperatively treated with a combination of sintilimab, trastuzumab, and chemotherapy at Hubei Cancer Hospital, China, from January 2022 to October 2023. Both preoperative and postoperative clinical and pathological characteristics of each patient were analyzed. The preoperative tumor stage was cT4N3M1.ResultsPostoperative pathological results showed that two patients achieved pathological complete remission (pCR), while the pathological stage in the other two patients decreased to ypT1N0M0 and ypT2N0M0. None of them had nerve or vascular invasion. None of the patients had recurrences or metastases until the last follow-up (October 2024) after primary surgery. The present case report suggests that a combination of immunotherapy comprising trastuzumab and chemotherapy can improve the efficiency of conversion therapy for patients with HER-2 positive locally advanced G/GEJ cancer. This study also demonstrates the safety of immune checkpoint inhibitors in a conversional treatment approach.ConclusionWe showed that a pathological complete response (pCR) can be obtained even with unresectable advanced GC through treatment with sintilimab combined with neoadjuvant chemotherapy and trastuzumab.

S-1/irinotecan/oxaliplatinchemotherapy achieved a pathological complete remission in advanced pancreatic carcinoma.

Chemotherapy has been developed for many years for malignancies, including advanced pancreatic cancer, downsizing the primary site, thereby enabling complete cure with the combination of conversion surgery. Pathological complete remission from operation samples was usually identified as a promising indication for a good prognosis for many carcinomas. Several case reports consisting of pathological complete remission after chemotherapy application have been reported but no case of pathological complete remission that resulted from successful extensive resection by surgery after S-1, irinotecan, and oxaliplatin (SIROX) chemotherapy. A 48-year-old male patient was hospitalized due to abdominal pain which turned out to be a 25mm-sized advanced uncinate process of pancreatic cancer with possible duodenum invasion and hepatic metastasis. The tumor had decreased after administering 23 sessions of modified SIROX chemotherapy, and he underwent pylorus-preserving pancreaticoduodenectomy with portal vein resection. He was successfully managed with conservative treatment and discharged 12days postoperatively despite his postoperative weakness. He had been taking S-1 pills for 6months and until now, 3years postoperatively, with no relapse. The final pathology reported complete tumor regression. Therefore, we emphasize the oncologic significance of chemotherapy in the uncinate process of pancreatic cancer and the potential role of conversion surgery.

Transarterial Infusion Chemotherapy and Embolization for Patients With Unresectable Advanced Cancer of Stomach or Gastroesophageal Junction: A Retrospective Study.

The feasibility of transarterial infusion chemotherapy and embolization (TAICE) in the treatment of advanced gastric cancer remains unclear. This study explored the value of TAICE in patients with unresectable locally advanced or metastatic cancer of stomach or gastroesophageal junction (GEJ). Patients with unresectable gastric cancer who received TAICE for tumor hemorrhage cessation were enrolled in this retrospective study. TAICE was performed using the Seldinger method. The tumor feeding artery was selected for infusion chemotherapy and then was embolized by microspheres or gelatin sponge. Patients involved in this study received one to four cycles TAICE with one to three drugs in the regimen. The possibility of surgery was evaluated after TAICE. Objective response rate (ORR), disease control rate (DCR), R0 resection rate, pathological complete remission (pCR) rate, major pathological remission (MPR) rate, progression-free survival (PFS), overall survival (OS), and safety were analyzed. Between January 2015 and December 2020, a total of 27 patients received a median of 2 (range, 1-4) cycles of TAICE. ORR and DCR were 33.3% and 74.0%, respectively. Eighteen patients received surgery, and 15 of them underwent gastrectomy and D2 lymph node dissection, with an R0 resection rate of 83.3% (15/18). Four (26.7%, 4/15) patients achieved MPR, but none achieved pCR. The median PFS was 19.8 months (95%CI, 12.1-40.0), and the median OS was 36.1 months (95%CI, 21.0-not reached). Patients with gastrectomy had significantly longer PFS (40.0 vs. 9.5 months, p < 0.0001) and OS (not reached vs. 16.6 months, p < 0.0001) than those without gastrectomy. All the TAICE-related adverse events were manageable, with the most common being fatigue (100%), nausea (63.0%), and vomiting (55.6%). No severe surgical complications occurred. TAICE was well-tolerated and could be a potential therapy to provide opportunity of surgery for patients with unresectable advanced gastric or GEJ cancer.

Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma

BackgroundThe current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma.MethodsPatients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety.ResultsForty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1–28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3–4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034–0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not.ConclusionsConversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma.

Neoadjuvant Chemotherapy With the Angiogenesis Inhibitor Bevacizumab for Locally Advanced Cervical Cancer.

We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy - whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven - could optimize the therapy regimen, leading to improved response rates and survival outcomes. Forty patients with histologically confirmed cervical cancer with FIGO stage IB3-IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated. Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progression-free survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098). While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach.

Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center.

Breast cancer is a primary cause of cancer-related death among women worldwide. Neoadjuvant chemotherapy (NACT) is a cornerstone treatment for locally advanced, non-metastatic breast cancer. Achieving pathological complete response (pCR) is often used as a surrogate marker for long-term outcomes. This study examines the impact of obesity, defined by a body mass index (BMI) over 30kg/m2, on achieving pCR in patients with early stage breast cancer (eBC) undergoing NACT. A retrospective analysis was conducted on patients with eBC treated with NACT at the University of Tübingen. The primary objective was to assess the impact of obesity on achieving pCR. Logistic regression analysis was used to determine the association between pre-treatment BMI and pCR, adjusting for covariates such as age, tumor stage, grading, and chemotherapy intensity. The study included 325 patients, with 24% classified as obese. While the univariate logistic regression analysis showed no significant impact of obesity on the odds ratio of achieving pCR, the multivariate analysis, accounting for covariates, demonstrated that obese patients had a significantly higher likelihood of achieving pCR. In this retrospective study, obesity significantly affected the likelihood of achieving pCR in patients with eBC cancer undergoing NACT after adjusting for covariates. While obesity is a known risk factor for breast cancer development and progression, its impact on the efficacy of NACT in terms of achieving pCR was positive in our study. These findings contribute to the ongoing debate in the literature, though the retrospective design and potential uncontrolled factors should be considered.

The dyslipidemic effect of cytostatics in the treatment of early breast cancer as a serious risk factor of cardiovascular diseases.

The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.

Two versus three to four cycles of neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma in real-world practice.

There is currently no consensus on whether intensive cycles of neoadjuvant immunochemotherapy provide greater benefit than do less intensive cycles (two cycles) in esophageal cancer (EC). Therefore, in this study, we assessed the efficacy and safety of three to four cycles of neoadjuvant immunochemotherapy compared to two cycles for treating patients with locally advanced esophageal squamous cell carcinoma (ESCC). This is a retrospective study of patients enrolled on previous clinical studies involving locally/regionally advanced ESCC (St. II-IVA) who received preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2021. In this study, patients were planned to receive 2-4 cycles of chemoimmunotherapy. In this secondary analysis, patients who received three to four cycles of neoadjuvant immunochemotherapy were compared to those receiving two cycles in terms of safety and oncologic outcomes. The follow-up duration required for inclusion was at least one year following surgery, or until the patient died or independently elected to cease treatment if less than one year. Our study identified a total of 142 participants, who were categorized into two groups based on the number of neoadjuvant treatment cycles: the two cycles group (2 cycles) (n=65) and the three to four cycles group (3-4 cycles) (n=77). Regarding the rate of major pathologic response (MPR), the rates for the 3-4 cycles and 2 cycles groups were 22.1% and 20.0%, respectively, although this difference was not statistically significant (P=0.25). Similarly, the rate of pathologic complete remission (pCR) was higher in the 3-4 cycles group at 14.3% compared to 7.7% in the 2 cycles group, but the difference did not reach statistical significance (P=0.07). However, the incidence of adverse events (AEs) classified as grade 3 or 4 was significantly higher in the 3-4 cycles group than in the 2 cycles group (36.4% vs. 18.5%; P=0.02). The median disease-free survival (DFS) for the 3-4 cycles group was 30.8 months [95% confidence interval (CI): not reached to not reached] and was not reached in the 2 cycles group (hazard ratio 2.35, 95% CI: 1.134-4.86; P=0.02). The 2 cycles group did not reach the median overall survival (OS) (hazard ratio 2.47, 95% CI: 1.08-5.53; P=0.045), with that in the 3-4 cycles group 34.9 months (95% CI: 24.5 to not reached). Interestingly, the survival outcomes were more favorable in the 2 cycles group for certain subgroups of patients: those who were male, those with a history of smoking, those with a history of drinking, and those who did not achieve MPR. Two cycles of neoadjuvant immunochemotherapy can be considered in locally advanced ESCC at high risk of developing toxicity with 3-4 cycles with similar oncologic outcomes.

Treatment Outcomes after Postoperative Radiotherapy in Triple-Negative Breast Cancer: Multi-Institutional Retrospective Study (KROG 17-05).

We designed a multi-institutional retrospective study to investigate the previously unreported failure pattern, survivals, and prognostic factors after postoperative radiotherapy (PORT) in triple negative breast cancer (TNBC) patients in South Korea. We retrospectively reviewed 699 patients with TNBC who underwent PORT at six institutions between 2008 and 2010. The median follow-up period was 94 months (range: 7-192 months). There were 216, 380, and 100 patients in stages I, II, and III, respectively. After 94 months post-treatment, all patients with pathologic complete remission after neoadjuvant chemotherapy were alive without any failure. Distant metastasis was the main cause of failure. The 5-year overall survival rate was 91.4%, 5-year loco-regional relapse-free survival rate (LRRFS) was 92.3%, 5-year distant metastasis-free survival rate (DMFS) was 89.4%, and 5-year disease-free survival rate (DFS) was 85.2%. On multivariate (Cox) analysis, T and N stages were significant prognostic factors for survival, and lympho-vascular invasion (LVI) was a significant factor for LRRFS and DMFS. Ki-67 expression was significantly associated with LRRFS and DFS. We verified that T and N stages, LVI, and Ki-67 expression were significantly associated with survival outcomes after PORT in TNBC.

625. PHASE II TRIAL OF INDUCTION CHEMOTHERAPY FOLLOWED BY CHEMORADIATION AND MINIMALLY INVASIVE SURGERY FOR LOCALLY ADVANCED CARCINOMA OF THE ESOPHAGUS

Abstract Background Most patients with esophageal cancer (EC) present locally advanced disease. Currently, multimodal strategies as neoadjuvant chemoradiotherapy or perioperative chemotherapy are employed, but still have high local and distant failures rates. This study evaluated the results of a phase II protocol with induction chemotherapy (IC) and concurrent chemoradiation (CR) before surgery for locally advanced carcinoma of the esophagus and esophagogastric junction (EGJ). The primary end point was to evaluate pathological complete remission (PCR) rate at surgical specimen. A PCR ≥ 30% was considered promising for further study. Methods Patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus and JEG, clinical stage T1b-3, N0-2, M0, PS 0-2, underwent two cycles of IC with carboplatin and paclitaxel followed by CR with the same agents and minimally invasive esophagectomy. At the screening, 14 days after the first cycle of IC and 6-8 weeks after the CR, metabolic responses were accessed by PET-CT and classified according the PERCIST criteria. Results One hundred and twenty-nine patients were accrued from January 2017 to April 2023. Forty-seven patients started the trial and 45 completed the neoadjuvant part of the protocol. Most patients were male (73.3%), the median age of was 55 years and AC was the most prevalent histological subtype (53.3%). Grade 3/4 toxicity during IC were infrequent and included neutropenia (12.5%), anemia (6.2%) and dysphagia (10.4%). Lymphopenia (10.7%) and dysphagia (6.5%) were the most common grade 3/4 toxicity during CR. All cases received the full radiotherapy dose of 45 Gy by IMRT technique. Thirty-seven patients underwent surgery and 31 had minimally invasive MacKeown esophagectomy with complete tumor resection (R0). Sixty-four percent of all included patients completed the neoadjuvant therapy and survived for 30 days after surgery. The most prevalent postoperative complications were anastomotic fistula (29%) and pneumonia (19%). Median hospital stay was 12 (7-56) days. Six patients (19.3%) had major postoperative morbidity (Clavien-Dindo ≥ IIIb), 4 were reoperated and one (3.2%) died during hospitalization. The median number of lymph nodes retrieved was 24. Eleven patients (33.5%) had pathological positive lymph nodes. The overall pathological complete response rate was 25.8%, 41.8% for SCC and 15.8% for AC. The early metabolic evaluation by PERCIST showed that 2 cases (4.4%) had progressive disease (PD), 26 (57.7%) stable disease (SD), 15 (33.3%) partial response (PR) and 2 (4.4%) complete response (CR). All the CR were SCC. The late metabolic response analysis showed that 1 (2.4%) patient had PD, 6 (14.6%) SD, 23 (56%) PR and 11 (27%) CR. On the basis of an intention-to-treat analysis, the median overall survival was 31.4 months, whereas the five-year overall survival was 31.2%. After curative surgery, 12 patients had recurrence disease. Six (19%) patients had recurrences at distant sites, 4 (12.9%) had loco-regional recurrence and 2 (6.4%) had both patterns. Conclusion This intensified neoadjuvant regimen was efficacious and safe in patients with locally advanced EC, but failed to reach the defined efficacy goal for further investigation, especially for AC.

Analysis of the Safety and Effectiveness of Lenvatinib + TACE-HAIC + PD-1 Inhibitor for Intermediate and Advanced Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the fourth leading cause of cancer death in the world. Aims: This study aimed to investigate the efficacy and safety of Lenvatinib + PD-1 inhibitor + TACEHAIC (LePTaHAIC) versus Sorafenib + TACE (SorTACE) for patients with intermediate and advanced HCC. Methods: In this retrospective study, patients diagnosed with BCLC stage B/C HCC were included. All patients were treated with LePTaHAIC (LePTaHAIC group) or SorTACE (SorTACE group) between September 2019 and September 2020. Outcomes, including progression-free survival (PFS), conversion surgical resection rate, objective remission rate (ORR), overall survival (OS), and treatment-related adverse events (AEs) were analyzed and compared between the two treatment modalities. Results: In total, 65 eligible patients were recruited, with 35 assigned to receive LePTaHAIC and 30 assigned to undergo SorTACE. Median PFS (11.4 vs. 5.13 months) and OS (26 vs. 10.08 months) in the LePTaHAIC group were significantly higher compared to the SorTACE group (both P &lt; 0.0001). The ORR (mRECIST standard) of the LePTaHAIC group was markedly higher compared to the SorTACE group (71.4% vs. 40%, P = 0.01). In the LePTaHAIC group, 11 patients underwent surgical resection (BCLC stage B: n = 4, BCLC stage C: n = 7) and 3 patients achieved complete pathological remission (pCR), while one patient in the SorTACE group underwent surgical resection. The conversion surgical resection rate of the LePTaHAIC group was significantly higher compared to the SorTACE group [31.4% (11/35) vs. 3.3% (1/30), P = 0.004]. Patients with LePTaHAIC had more frequent grade 3-4 treatmentrelated AEs, especially thrombocytopenia, compared to the SorTACE group (22.9% vs. 3.3%, P = 0.02). Conclusion: LePTaHAIC exhibited acceptable toxic effects and improved survival compared to SorTACE in intermediate and advanced HCC.

623. PERIOPERATIVE THERAPY FOR LIMITED-STAGE SMALL CELL ESOPHAGEAL CARCINOMA: A RETROSPECTIVE COHORT STUDY

Abstract Background The optimal treatment strategy for limited-stage small cell esophageal carcinoma (LS-SCEC) remains uncertain, we aimed to evaluate the efficacy of perioperative therapy in those patients. Methods From June 2005 to November 2022, a total of 156 patients with LS-SCEC who underwent esophagectomy were included in the current study. The primary endpoint was overall survival, and secondary endpoints included progression-free survival. Pathologic staging was determined based on the 8th American Joint Committee on Cancer (AJCC) TNM staging system for esophageal carcinoma. Survival curves were created using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors analysis was carried out using both univariate and multivariate Cox regression models, as well as propensity score matching (PSM) analysis. Statistical significance was defined as P value &amp;lt; 0.05 in a two-tailed test. Results Among 156 LS-SCEC patients, the median age was 62 years (interquartile range [IQR], 56-67), with 120 (76.9%) being males. Thirty-three (21.2%) patients received neoadjuvant chemotherapy; and 2 (1.3%) received neoadjuvant chemoradiotherapy. Seventy-six (48.7%) received adjuvant chemotherapy, 2 (1.3%) received adjuvant radiotherapy, and 13 (8.3%) received adjuvant chemoradiotherapy. Only 7 (4.5%) patients achieved pathological complete remission after neoadjuvant therapy. Following surgery, 33 (21.2%) patients were categorized stage I, 40 (25.6%) as stage II, 61 (39.1%) as stage III, and 22 (14.1%) as stage IV. The median follow-up time of the entire cohort was 72 months. The median disease-free survival (mDFS) was 12.0 months (95% CI, 10.2–13.8 months), and the median overall survival (mOS) was 21.0 months (95% CI, 16.2–25.8 months). The 5-year OS rate was 25.9%, and the DFS rate was 21.9%. Univariate analysis revealed that clinical T stage (P=0.011), clinical N stage (P=0.009), pathological T stage (P=0.027), pathological N stage (P=0.001), pathological TNM stage (P=0.002), adjuvant therapy (P&amp;lt;0.001), and neural invasion (P=0.001) were significant prognostic factors for overall survival. In multivariate analysis, clinical T stage (P=0.049), neural invasion (P=0.002), N stage (P=0.006), and adjuvant therapy (P=0.001) were identified as independent prognostic factors. Furthermore, a PSM analysis was conducted to evaluate the impact of neoadjuvant chemotherapy on LS-SCEC patients. Following PSM, 64 patients were matched, with 32 in each group. Both univariate and multivariate analyses indicated that neoadjuvant chemotherapy could enhance the OS of LS-SCEC patients, with a 5-year OS rate of 37.7% compared to 0.0% in the non-neoadjuvant chemotherapy group (P&amp;lt;0.001, HR=0.319, 95% CI: 0.168-0.604). Subgroup analyses further supported the benefit of neoadjuvant chemotherapy for patients with clinical stages T3-4 and nodal positive (N+), where improved outcomes were observed (P=0.001 and 0.013 respectively). Additionally, subgroup analyses revealed that adjuvant chemoradiotherapy was identified as the optimal treatment model for patients with nodal positive status (adjuvant chemoradiotherapy vs. chemotherapy: OS P=0.01, DFS P=0.004) and those categorized as pathological stage III-IV (adjuvant chemoradiotherapy vs. chemotherapy: OS P=0.03, DFS P=0.017). Conclusions Perioperative therapy is essential for patients with LS-SCEC. Patients with clinical stage T3-4 and nodal positive should undergo neoadjuvant chemotherapy. All patients should receive adjuvant therapy, and adjuvant chemoradiotherapy is recommended for those with nodal involvement or pathologic TNM stages III-IV.

Locoregional recurrence in studies of primary systemic therapy in early invasive breast cancer

IntroductionThe use of primary systemic therapy (PST) in early invasive breast cancer is routine but there are concerns about risk of locoregional recurrence. MethodsWe conducted a systematic literature review to identify studies of locoregional treatment and recurrence in patients with early invasive breast cancer who received non-endocrine PST. ResultsWe identified 112 studies (18 prospective trials and 94 non-interventional studies). The use of surgery and radiotherapy after PST was recorded in 65 (58 %) and 50 (45 %) of studies respectively. 66 (59 %) studies reported locoregional recurrence. Cumulative 5-year locoregional recurrence risks varied from 1 % to 23 %. Locoregional recurrence was higher in patients under the age of 40, those who did not achieve a pathological complete remission after PST, had ER-negative or HER2 negative tumours, were recorded to have inoperable disease before PST, and did not have radiotherapy. LRR rates in these studies have not fallen over the overall calendar period of patient enrollment (1999–2016). ConclusionThe recording of locoregional treatments and outcomes is suboptimal in studies of PST and efforts to improve this are required. In the absence of randomised evidence, our findings may help to inform care and guideline development. We were unable to exclude concern that the use of PST is associated with a higher than desired risk of locoregional recurrence.

Factors associated with pathological complete remission after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world clinical setting.

This study aims to identify factors associated with achieving a pathological complete remission (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). We conducted a cohort analysis of 171 LARC patients who underwent curative resection post-nCRT at the First Affiliated Hospital of Guangxi Medical University between January 2015 and December 2021. The data encompassed clinical and pathological information. Univariate and binary logistic regression multivariate analyses were employed to examine the factors influencing pCR achievement after nCRT. Kappa value tests were utilized to compare clinical staging after nCRT with postoperative pathological staging. Postoperative histopathology revealed that of the 171 patients, 40 (23.4%) achieved TRG 0 grade (pCR group), while 131 (76.6%) did not achieve pCR, comprising 36 TRG1, 42 TRG2, and 53 TRG3 cases. Univariate analysis indicated that younger age (p=0.008), reduced tumor occupation of intestinal circumference (p =0.008), specific pathological types (p=0.011), and lower pre-nCRT CEA levels (p=0.003) correlated with pCR attainment. Multivariate analysis identified these factors as independent predictors of pCR: younger age (OR=0.946, p=0.004), smaller tumor occupation of intestinal circumference (OR=2.809, p=0.046), non-mucinous adenocarcinoma pathological type (OR=10.405, p=0.029), and lower pre-nCRT serum CEA levels (OR=2.463, p=0.031). Clinical re-staging post-nCRT compared to postoperative pathological staging showed inconsistent MRI T staging (Kappa=0.012, p=0.718, consistency rate: 35.1%) and marginally consistent MRI N staging (Kappa=0.205, p=0.001, consistency rate: 59.6%). LARC patients with younger age, presenting with smaller tumor circumferences in the intestinal lumen, lower pre-nCRT serum CEA levels, and non-mucinous adenocarcinoma are more likely to achieve pCR after nCRT. The study highlights the need for improved accuracy in clinical re-staging assessments after nCRT in LARC.

Development and validation of a neoadjuvant chemotherapy pathological complete remission model based on Reg IV expression in breast cancer tissues: a clinical retrospective study

ObjectiveTo develop and authenticate a neoadjuvant chemotherapy (NACT) pathological complete remission (pCR) model based on the expression of Reg IV within breast cancer tissues with the objective to provide clinical guidance for precise interventions.MethodData relating to 104 patients undergoing NACT were collected. Variables derived from clinical information and pathological characteristics of patients were screened through logistic regression, random forest, and Xgboost methods to formulate predictive models. The validation and comparative assessment of these models were conducted to identify the optimal model, which was then visualized and tested.ResultFollowing the screening of variables and the establishment of multiple models based on these variables, comparative analyses were conducted using receiver operating characteristic (ROC) curves, calibration curves, as well as net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Model 2 emerged as the most optimal, incorporating variables such as HER-2, ER, T-stage, Reg IV, and Treatment, among others. The area under the ROC curve (AUC) for Model 2 in the training dataset and test dataset was 0.837 (0.734–0.941) and 0.897 (0.775–1.00), respectively. Decision curve analysis (DCA) and clinical impact curve (CIC) further underscored the potential applications of the model in guiding clinical interventions for patients.ConclusionThe prediction of NACT pCR efficacy based on the expression of Reg IV in breast cancer tissue appears feasible; however, it requires further validation.

Comprehensive Evaluation of a Levonorgestrel Intrauterine Device (LNG-IUD), Metformin, and Liraglutide for Fertility Preservation in Endometrial Cancer: Protocol for a Randomized Clinical Trial.

Endometrial cancer is a leading gynecological malignancy, with obesity being a significant risk factor due to increased estrogen production in body fat. Current treatments often involve hysterectomy, which precludes fertility, thus highlighting the need for fertility-preserving options. This study aims to evaluate the combined efficacy of a levonorgestrel intrauterine device (LNG-IUD), metformin, and liraglutide for treating women with endometrial hyperplasia or early stage endometrial cancer while preserving fertility. The study will enroll 264 women aged 18-45 with a BMI > 30 who desire uterine preservation. Participants will be randomized into three groups: LNG-IUD alone, LNG-IUD plus metformin, and LNG-IUD plus metformin and liraglutide. Primary outcomes will include complete pathological remission, while secondary outcomes will assess histological changes, glucose, insulin levels, and weight changes over a 12-month period. This study protocol hypothesizes that LNG-IUD combined with metformin and liraglutide may potentially lead to higher regression rates of endometrial hyperplasia (EH) and early stage endometrial cancer (EC) compared to LNG-IUD alone. Furthermore, the protocol anticipates that these combination therapies will demonstrate good tolerability with minimal adverse effects, suggesting the potential benefit of integrating metabolic interventions with LNG-IUD to enhance treatment efficacy while preserving fertility in women with EH and EC.

Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for locally advanced head and neck squamous cell carcinoma

PurposeAnatomical structures and organ preservation concepts of the head and neck are important for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Neoadjuvant chemotherapy has been applied to improve organ preservation; however, pathological complete remission is still unsatisfactory. The purpose of this study was to explore the pathological complete response (pCR) rate and safety of immune checkpoint blockade combined with neoadjuvant chemotherapy (NAC) in patients with LA HNSCC.MethodsFifty-one patients participated in this retrospective study, and of these, 25 received NAC only (cisplatin+5-fluorouracil+nab-paclitaxel), and 26 received NAC (cisplatin+5-fluorouracil) plus pembrolizumab. Pathological complete remission, the objective response rate (ORR), delayed surgery and toxicity were compared between the two groups.ResultsA significant difference was observed in the pCR rate and ORR between the NAC+ICB group and the NAC group. Delaying surgery and Grade 3 or 4 AEs occurred more frequently in the NAC group. In the NAC-only group, during a median follow-up period of 31.80 months, the recurrence-free survival (RFS) rate was 80.0%, the disease-free survival (DFS) rate was 80.0% and the overall survival (OS) rate was 88.0%. In the NAC+ICB group, during the median follow-up period of 22.99 months, the RFS rate was 96.2%, the DFS rate was 96.2% and the OS rate was 100%.ConclusionThe combination of pembrolizumab with NAC could improve the pathological response without increasing the risk of toxicity, which provides pathological evidence for the treatment of LA HNSCC patients with NAC+ICB.

Comparison of immunochemotherapy and chemotherapy alone in conversion therapy for locally advanced unresectable esophageal squamous cell carcinoma.

The clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear. Retrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed. The results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006). Compared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

Analysis of factors affecting complete pathological remission after neoadjuvant immunocombination chemotherapy treatment for locally advanced esophageal squamous carcinoma.

e16061 Background: Chemotherapy combined with immunotherapy for locally advanced esophageal squamous carcinoma has achieved a high rate of complete pathological remission, which is conducive to a better prognosis for patients; however, not all ESCC patients benefit from ICI therapy, so finding validated prognostic markers of efficacy will help us to screen for populations that are superior to neoadjuvant immunotherapy. Methods: Patients with locally advanced esophageal squamous carcinoma treated with neoadjuvant immune-combination chemotherapy followed by radical surgery from January 2019 to June 2023 at our institution were collected. The grouping was based on whether pathologic complete remission (pCR) was achieved after neoadjuvant therapy. Clinical and treatment-related data as well as hematologic, inflammatory, and nutritional indices within 1 week before neoadjuvant therapy and within 1 week after 2 cycles of neoadjuvant immune-combination chemotherapy treatment were collected from all patients, and univariate and multivariate analyses were performed to assess independent predictors of pCR. Results: Patients in both pCR and Non-pCR groups were more likely to obtain pCR if they had pre-treatment BMI &gt; 21Kg/m2 vs BMI ≤21Kg/m2, number of neoadjuvant therapy cycles ≥3 cycles vs number of neoadjuvant therapy cycles = 2 cycles, and CYFRA21-1ng/ml &lt; 3.28 vs ≥3.28 before neoadjuvant therapy (p &lt; 0.05). Patients with albumin ≥40.10g/L vs albumin &lt; 40.10g/L, NLR &lt; 2.50 vs NLR ≥2.50, and NRI ≥98.06 vs NRI &lt; 98.06 were more likely to achieve pCR before treatment in both groups (p &lt; 0.05). SII ≥521.75 VS SII &lt; 521.75 was more likely to achieve pCR after 2 cycles of treatment (p &lt; 0.05). Univariate analysis of the comparison of dynamic changes in nutritional inflammatory indexes during treatment between the two groups of patients showed that pCR was more likely to be achieved in patients with persistently elevated eosinophil counts and NLR after 2 cycles of neoadjuvant immune-combination chemotherapy treatment (p &lt; 0.05). The results of multifactorial analysis showed that pre-treatment BMI, SII after 2 cycles of treatment, and dynamic changes in eosinophils during neoadjuvant therapy were independent influences on complete pathological remission after neoadjuvant immune-combination chemotherapy treatment (p &lt; 0.05). Conclusions: Complete pathological remission after neoadjuvant immune-combination chemotherapy treatment for esophageal squamous carcinoma was significantly correlated with the patient's pre-treatment BMI, Post-treatment SII, and eosinophil dynamics during treatment.

Prediction models of locally advanced rectal cancer prognosis incorporating perioperative longitudinal clinical data: A retrospective longitudinal cohort study.

e15624 Background: For locally advanced rectal cancer, neoadjuvant chemoradiation(CCRT) followed by surgery is a standard treatment. Clinical T/N stage, whether pathological complete remission (pCR) after neoadjuvant CCRT or not are well recognized tumor features that predict disease prognosis. Although the parameters that determine pathologic stage are the strongest predictors of postoperative outcome, other clinical, molecular, and histologic features may influence prognosis independent of stage. The aim is to compare the predictive efficiency, between different models for overall survival in rectal cancer patients. Methods: This retrospective study is approved by TMU-JIRB(Protocol Number: N201809032).This is also a single institute study. 175 newly-diagnosed patients with locally advanced rectal cancer were retrospectively enrolled between Jan.2011 and Dec.2016. Basic information include sex, age, body weight, body height, previous medical history were recorded. CEA level, chemotherapy regimen, type of surgery, and distance between tumor and anal verge were also collected. Chemotherapy regimen of CCRT including 5FU+LV, capecitabine (Xeloda), FOLFOX, and FOLFIRI are recorded. Surgical resection was then followed 4-8 weeks after completion of CCRT. The 2010 AJCC tumor response grading (TRG) system was used to report treatment response of proctectomy samples. The progression free survival (PFS) and overall survival (OS) are then calculated. PFS is defined as survival without any recurrence or distant metastasis before Dec 31st, 2023. A comprehensive evaluation was conducted by incorporating all these machine learning models together. The aim was to compare their predictive efficiency, with models such as Random Forest, Naïve Bayes, KNeighbor, SVM, Decision Tree, Logistic Regression, XGBoost, and LightGBM. Results: 175 patients (104 men and 71 women) were enrolled in this study. The median follow up time was 7.1 yrs. The BMI was 24.05 ± 0.03 for men and 24.20 ± 0.07 for women. 32 (17.3%) patients achieved pCR, TRG 0. Clinical staging cT3 (78.8%) and nodal positive (78.8%) are the most common tumor feature in this study group. The median age of male and female patient is 58.6 and 56.1 respectively. Upon applying various machine learning models, different predictive accuracies emerged. The Random Forest, KNeighbor, and SVM models all achieved an accuracy of 0.9250. Naïve Bayes had an accuracy of 0.8620, while the SVC model registered at 0.9310, and XGBoost was slightly behind at 0.9286. SVC model is marking the best-performing model in this evaluation. Conclusions: This multicenter retrospective data-driven deep learning prediction model informed that SVC model yielded the best predictive results. Further prospective clinical trials and external validation of this prediction model are needed to further reinforce our findings.