Pathologic response evaluation of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy: a clinical trial.

Objective: Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). Methods: This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Results: Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Conclusion: Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. Clinical trial registration: https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.

Neoadjuvant immunotherapy leads to complete pathologic response in locally advanced colon cancer.

Immunotherapy is considered first line in patients with dMMR metastatic colorectal cancer (CRC). Recent studies have also shown promising results with neoadjuvant immunotherapy in locally advanced CRC. We report a case in which neoadjuvant immunotherapy with pembrolizumab resulted in complete pathologic response at time of resection as well as saved the patient the morbidity associated with a hepatectomy. We also completed a scoping review of the literature which suggests promising tumor responses with treatment in dMMR CRC. Further randomized control trials to determine the magnitude of response and optimal regimen are needed.

Dynamic Anthropometrics in Pancreatic Cancer: Associations Between Body Composition Changes During Neoadjuvant Therapy and Survival Outcomes After Resection.

BACKGROUND: Assessment of individual tumor biology and response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. The significance of anthropometric (body composition) changes during chemotherapy as a surrogate for tumor biology in the setting of localized PDAC is unknown. METHODS: A retrospective, single-institution analysis of patients with PDAC who received neoadjuvant therapy (NAT) and pancreatectomy from 2017 to 2021 was performed. Radiologic anthropometric analysis used artificial intelligence-driven software to segment and compute total and sub-compartment muscle area, adipose tissue area, and attenuation values at the level of the L3 vertebra. Kaplan-Meier survival estimates, log-rank tests, and multivariable Cox regression models were used in survival analyses. RESULTS: The inclusion criteria were met by 138 patients. Although decreases in muscle and adipose tissue areas during NAT were predominant, a subset of patients experienced an increase in these compartments. Increases in muscle greater than 5% (hazard ratio [HR], 0.352; 95% confidence interval [CI] 0.135-0.918; p = 0.033) and increases in adipose tissue greater than 15% (HR, 0.375; 95% CI 0.144-0.978; p = 0.045), were significantly associated with improved survival, whereas loss of visceral fat greater than 15% was detrimental (HR 1.853; CI 1.099-3.124; p = 0.021). No significant associations with single time-point anthropometrics were observed. Gains in total muscle and adipose mass were associated with improved pathologic response to systemic therapy and less advanced pathologic tumor stage. CONCLUSIONS: Dynamic anthropometric analysis during NAT for PDAC is a stronger prognostic indicator than measurements taken at a single point in time. Repeated anthropometric analysis during preoperative chemotherapy may serve as a biomarker for individual tumor biology and response to therapy.

Complete pathologic response in esophageal adenocarcinoma: does it make a difference?

Advancements in neoadjuvant regimens for esophageal adenocarcinoma have enabled some patients to achieve complete pathologic response at time of esophagectomy. There are currently limited data detailing this trend or the implications of complete pathologic response on survival. The National Cancer Database was used to identify 16,169 patients with esophageal adenocarcinoma that received trimodal therapy including esophagectomy between 2006 and 2020. Of these, 11.4% had complete pathologic response at esophagectomy. Patient factors, staging characteristics, and survival trends were evaluated. In patients diagnosed between 2016 and 2020, the rate of complete pathologic response was 17.5%. Female sex (OR 1.295, 95% CI 1.134-1.481, p = 0.0001), Black race (OR 1.729, 95% CI 1.362-2.196, p = 0.0002), Hispanic ethnicity (OR 1.418, 95% CI 1.073-1.875, p = 0.0141), and later era of diagnosis (2016-2020 OR 2.898, 95% CI 2.508-3.349, p < 0.0001) were independent predictors of complete pathologic response. Clinical stage II disease was associated with an increased probability of complete pathologic response (OR 1.492, 95% CI 1.19-1.871) while clinical stage III disease had a decreased probability of complete pathologic response (OR 0.762, 95% CI 0.621-0.936, p < 0.0001). Complete pathologic response conveyed a strong survival benefit, with a median survival of 86.4 months (95% CI 73.9-102.1) versus 30.7 months (95% CI 29.8-31.7, p < 0.0001) in those without complete pathologic response. Four-year median survival was also higher in those with complete pathologic response (63.3%, 95% CI 60.8-66.0% vs. 39.2%, 95% CI 38.4-40.1%, p < 0.0001). In summary, complete pathologic response is associated with a profound survival advantage in patients with esophageal adenocarcinoma. Such knowledge carries implications for patient counseling, prognostication, and surveillance and demonstrates a need for improved identification of complete clinical response prior to esophagectomy.

Pathologic Response and Survival after Neoadjuvant Chemotherapy with Bevacizumab Followed by Surgery for Clinical Stage II/IIIA Nonsquamous Non-Small-Cell Lung Cancer: Results from a Phase II Feasibility Study (NAVAL).

The objective of this study was to evaluate the relationship between pathologic response and survival in patients with clinical stage II/IIIA nonsquamous non-small-cell lung cancer (NSCLC) who intended to undergo neoadjuvant chemotherapy with bevacizumab, followed by surgery. In this phase II NAVAL study evaluating the feasibility of neoadjuvant chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg), followed by surgery, progression-free survival (PFS) and overall survival (OS) were assessed as the secondary endpoints. Patients were categorized based on the proportion of residual viable primary tumor in the resected specimen after neoadjuvant chemotherapy: those with residual tumor in less than one-third were classified as pathologic responders, the rest as nonresponders. Of the 30 patients, 25 underwent surgical resection after three cycles of neoadjuvant chemotherapy with bevacizumab; 5 did not undergo surgery. Among all 30 patients, the rates of 2- and 5-year PFS were 41.5% and 34.6%, respectively, and the rates of 2- and 5-year OS were 70.0% and 60.0%, respectively. A total of 6 patients (20%) were classified as pathologic responders; the other 24 (80%), as nonresponders. The five-year PFS differed significantly between pathologic responders (100%) and nonresponders (17.5%; p = 0.002). The five-year OS also differed significantly between pathologic responders (100%) and nonresponders (43.5%; p = 0.006). Pathologic response seems to be a predictor of survival. Long-term survival after surgery is expected for pathologic responders, whereas additional therapy is needed for nonresponders.

Combined transarterial chemoembolization and thermal ablation in candidates to liver transplantation with hepatocellular carcinoma: pathological findings and post-transplant outcome.

OBJECTIVES: Evaluating the pathological response and the survival outcomes of combined thermal ablation (TA) and transarterial chemoembolization (TACE) as a bridge or downstaging for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) > 3 cm. MATERIALS AND METHODS: A retrospective review encompassed 36 consecutive patients who underwent combined TA-TACE as bridging or downstaging before LT. Primary objectives included necrosis of the target lesion at explant pathology, post-LT overall survival (OS) and post-LT recurrence-free survival (RFS). For OS and RFS, a comparison with 170 patients subjected to TA alone for nodules <3 cm in size was also made. RESULTS: Out of the 36 patients, 63.9% underwent TA-TACE as bridging, while 36.1% required downstaging. The average node size was 4.25 cm. All cases were discussed in a multidisciplinary tumor board to assess the best treatment for each patient. Half received radiofrequency (RF), and the other half underwent microwave (MW). All nodes underwent drug-eluting beads (DEB) TACE with epirubicin. The mean necrosis percentage was 65.9% in the RF+TACE group and 83.3% in the MW+TACE group (p-value = 0.099). OS was 100% at 1 year, 100% at 3 years and 94.7% at 5 years. RFS was 97.2% at 1 year, 94.4% at 3 years and 90% at 5 years. Despite the different sizes of the lesions, OS and RFS did not show significant differences with the cohort of patients subjected to TA alone. CONCLUSIONS: The study highlights the effectiveness of combined TA-TACE for HCC>3 cm, particularly for bridging and downstaging to LT, achieving OS and RFS rates significantly exceeding 80% at 1, 3 and 5 years.

Optimizing perioperative treatment for potentially resectable stage III squamous cell lung carcinoma: promising results of a condensed four-cycle regimen with tislelizumaband chemotherapy.

BACKGROUND: The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. METHODS: Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. RESULTS: Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon-gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. CONCLUSIONS: A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05024266. Registered August 27, 2021.

Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma.

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%-90%, III: 91%-99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I-II; n = 15) and good responders (Grades III-IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.

Pathologic and survival outcomes following radical cystectomy for "progressive" and "de novo" muscle-invasive bladder cancer: A meta-analysis stratified by neoadjuvant chemotherapy status.

OBJECTIVE: To compare survival and pathologic outcomes in patients with progressive muscle-invasive bladder cancer (pgMIBC) and de novo muscle-invasive bladder cancer (dnMIBC) after radical cystectomy (RC), with a focus on the role of neoadjuvant chemotherapy (NAC). METHODS: A comprehensive literature search was conducted on PubMed and EMBASE databases to identify studies comparing pgMIBC to dnMIBC. Survival outcomes, including cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS), and pathologic outcomes (rates of ≤pT1, pT0, pT3/T4, and pN+ disease) were compared between pgMIBC and dnMIBC. RESULTS: The analysis included 19 cohorts from 16 studies, categorized into 3 groups based on NAC use: 1. patients who underwent RC and were all treated with NAC (RC + NAC only group); 2. patients who underwent RC, with or without NAC (RC +/- NAC group); 3. patients who only underwent RC without NAC (RC only group). Compared to dnMIBC, pgMIBC demonstrated worse outcomes for CSS, OS, and RFS. In the RC + NAC only group (3 cohorts), the hazard ratio (HR) for CSS was 1.52 (95% confidence interval [CI] = 1.05-2.2), while the HR for OS was 1.46 (95%CI = 1.05-2.02). Similarly, in the RC +/- NAC group (6 cohorts for CSS and 3 cohorts for OS), the HR for CSS was 1.27 (95%CI = 1.05-1.55), and the HR for OS was 1.27 (95%CI = 1.08-1.51). There were no significant differences observed in pathologic outcomes, including rates of ≤pT1, pT0, and pT3/T4 disease, across all subgroups. However, pgMIBC was associated with a higher risk of nodal metastatic (pN+) disease in the RC + NAC only group (4 cohorts, relative risk [RR] = 1.43, 95%CI = 1.12-1.84). CONCLUSIONS: The findings highlight the potentially worse prognosis in patients with pgMIBC compared to dnMIBC, even with the modern use of NAC. The study emphasizes the importance of careful patient counseling, further classification of patients for treatment selection, and the consideration of additional or innovative systemic therapies for pgMIBC.

Pathologic Response Evaluation in Neoadjuvant-Treated Lung Cancer.

Major pathologic response (MPR) and pathologic complete response (pCR) are increasingly being used in non-small cell lung carcinoma neoadjuvant clinical trials as an early endpoint of survival. MPR for all histologic types of lung cancer is ≤ 10% of viable tumor, while pCR requires no viable tumor. The International Association for the Study of Lung Cancer multidisciplinary recommendation for the assessment of response in surgically resected lung carcinomas after neoadjuvant therapy was the first attempt to standardize grossing processing and microscopic evaluation.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. AIM: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). METHODS: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. RESULTS: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. CONCLUSION: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Clinical factors and major pathological response after neoadjuvant chemoimmunotherapy in potentially resectable lung squamous cell carcinoma.

Objective: Major pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC. Methods: This retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups. Results: In total, 91 LUSC patients who met the study's eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pre-treatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001). Conclusion: The MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC.

Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC.

INTRODUCTION: Controversy remains as to whether pathologic complete response (pCR) and major pathologic response (MPR) represent surrogate end points for event-free survival (EFS) and overall survival (OS) in neoadjuvant trials for resectable NSCLC. METHODS: A search of PubMed and archives of international conference abstracts was performed from June 2017 through October 31, 2023. Studies incorporating a neoadjuvant arm with immune checkpoint blockade alone or in combination with chemotherapy were included. Those not providing information regarding pCR, MPR, EFS, or OS were excluded. For trial-level surrogacy, log ORs for pCR and MPR and log hazard ratios for EFS and OS were analyzed using a linear regression model weighted by sample size. The regression coefficient and R2 with 95% confidence interval were calculated by the bootstrapping approach. RESULTS: Seven randomized clinical trials were identified for a total of 2385 patients. At the patient level, the R2 of pCR and MPR with 2-year EFS were 0.82 (0.66-0.94) and 0.81 (0.63-0.93), respectively. The OR of 2-year EFS rates by response status was 0.12 (0.07-0.19) and 0.11 (0.05-0.22), respectively. For the 2-year OS, the R2 of pCR and MPR were 0.55 (0.09-0.98) and 0.52 (0.10-0.96), respectively. At the trial level, the R2 for the association of OR for response and HR for EFS was 0.58 (0.00-0.97) and 0.61 (0.00-0.97), respectively. CONCLUSIONS: Our analyses reveal a robust correlation between pCR and MPR with 2-year EFS but not OS. Trial-level surrogacy was moderate but imprecise. More mature follow-up and data to assess the impact of study crossover are needed.

Pre-hepatectomy dynamic circulating tumor DNA to predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in patients with colorectal liver metastases.

OBJECTIVE: To evaluate the predictive value of pre-hepatectomy dynamic circulating tumor DNA (ctDNA) on pathologic response to preoperative chemotherapy and recurrence after liver resection for colorectal liver metastases (CRLM). BACKGROUND: Pathologic response is a predictor of clinical outcomes for patients undergoing hepatectomy for CRLM. Postoperative ctDNA has been proven to be sensitive for recurrence detection. However, few studies investigate the impact of pre-hepatectomy ctDNA on pathologic response and recurrence. METHODS: Patients with potential resectable CRLM underwent preoperative chemotherapy and hepatectomy between 2018 and 2021 was considered for inclusion. Plasma ctDNA was collected before and after preoperative chemotherapy. Pathologic response was analyzed for all patients after liver resection. Recurrence free survival was compared between patients with different ctDNA status and different pathologic response. The relation between ctDNA and pathologic response was also analyzed. RESULTS: A total of 114 patients were included. ctDNA was detectable in 108 of 114 patients (94.7%) before chemotherapy, in 56 of 114 patients (49.1%) after chemotherapy. Patients with ctDNA positive at baseline and negative after chemotherapy had significantly longer RFS (median RFS 17 vs 7 months, p = 0.001) and HRFS (median HRFS unreached vs 8 months, p < 0.001) than those with ctDNA persistently positive after chemotherapy. Two patients (1.6%) had a pathologic complete response and 56 patients (45.2%) had a pathologic major response. Post-chemotherapy ctDNA- was associated with improved major pathologic response (53.4% vs 32.1%, p = 0.011). In the multivariable analysis, ctDNA- after chemotherapy (HR 0.51, 95% CI 0.28-0.93), major pathologic response (HR 0.34, 95% CI 0.19-0.62) and surgery combined with radiofrequency ablation (HR 2.62, 95% CI 1.38-5.00) were independently associated with RFS (all p < 0.05). CONCLUSIONS: Pre-hepatectomy dynamic monitoring of ctDNA could predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in CRLM patients. Negative ctDNA after preoperative chemotherapy was associated with better tumor regression grade and recurrence-free survival, which might be used to guide pre-hepatectomy chemotherapy and predict prognosis.

Outcomes and pathologic response of primary lung cancer treated with tyrosine kinase inhibitor/immune checkpoint inhibitor before salvage surgery.

PURPOSE: Advances in primary lung cancer drug therapy have extended patients' survival, including patients with stage IV disease. This study assessed the safety and effectiveness of salvage surgery following tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) therapy in primary lung cancer. METHODS: A retrospective chart review was conducted of 2050 primary lung cancer surgeries performed at our institution between 2012 and 2022. The study included patients who underwent salvage surgery for unresectable lesions that became resectable or localized residual lesions after treatment. We investigated patients' clinicopathological characteristics, therapeutic responses, and survival outcomes. RESULTS: We identified eight cases of salvage surgery after TKI treatment and eight cases after ICI treatment. Five patients experienced early recurrence after surgery; however, the long-term outcome in the post-TKI group was favorable, with a median overall survival (OS) of 66 (range: 28-80) months. Postoperative recurrence was confined to local lymph node recurrence in one patient in the post-ICI group. Despite the relatively short observation period, the long-term prognosis remained promising, with a median OS of 18.7 (range: 9.7-55.8) months. CONCLUSIONS: Salvage surgery after TKI or ICI treatment can be safely performed, and the OS may be favorable.

Neoadjuvant chemotherapy for breast cancer: Pathologic response rates but not tumor size, has an independent prognostic impact on survival.

AIM: We investigated the pathologic complete response rates (pCR) and survival outcomes of early breast cancer patients who underwent neoadjuvant chemotherapy (NAC) over 14 years at a French comprehensive cancer center and reported pCR and survival outcomes by tumor subtypes and size. METHODS: From January 2005 to December 2018, 1150 patients receiving NAC were identified. Correlations between cT stage, breast tumor response, axillary lymph node response, pCR, surgery, and outcomes were assessed. pCR was defined as (ypT0/ypTis) and (ypN0/pN0sn). RESULTS: A pCR was reached in 31.7% (365/1150) of patients and was strongly associated with tumor subtypes, but not with tumor size (pretreatment cT category). Luminal-B Her2-negative and triple-negative (TN) subtypes, cN1 status, older age, and no-pCR had an independent negative prognostic value. Overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) were not significantly different for cT0-1 compared to cT2 stages. In Cox-model adjusted on in-breast pCR and pN status, ypN1 had a strong negative impact (OS, RFS, and MFS: HR = 3.153, 4.677, and 6.133, respectively), higher than no in-breast pCR (HR = 2.369, 2.252, and 2.323). A negative impact of no pCR on OS was observed for cN0 patients and TN tumors (HR = 4.972) or HER2-positive tumors (HR = 11.706), as well as in Luminal-B Her2-negative tumors on MFS (HR = 2.223) and for Luminal-A on RFS (HR = 4.465) and MFS (HR = 4.185). CONCLUSION: Achievement of pCR, but not tumor size (pretreatment cT category), has an independent prognostic impact on survival. These results suggest potential NAC benefits in patients with small tumors (<2 cm), even in absence of clinically suspicious lymph nodes. Residual lymph node disease after NAC is the most powerful adverse prognostic factor.

Moderate hypofractionated radiation therapy and pathologic response for soft tissue sarcomas (STS) of limbs and trunk: experience from a tertiary cancer center

Background Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. Material and methods From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5–60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. Results All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1–2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1–40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002) (AU)

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.

OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer. METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology. RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis. CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.