Neoadjuvant Research Articles

DNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial.

Alterations in DNA damage response (DDR) genes, including ERCC2, have been correlated with response to neoadjuvant cisplatin-based chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). The SWOG 1314 (S1314) trial enrolled patients with MIBC who received one of two NAC regimens followed by radical cystectomy. We examined the prevalence of DDR alterations in NAC responders versus nonresponders and correlated DDR alteration status with response. Pretreatment tumor specimens from 179 evaluable patients underwent next-generation sequencing (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets assay). Associations were determined between any or only deleterious alterations within nine predefined DDR genes, or any alterations in ERCC2, and progression-free survival (PFS) and overall survival using Cox regression, and, in a subset of evaluable patients, pathologic response (complete response, pT0, or downstaging to <pT2) using logistic regression, adjusting for clinical stage and performance status. Deleterious DDR alterations were detected in 41 (23%) of 179 patients. Of the 151 patients evaluable for pathologic response, patients with deleterious DDR alterations (n = 39) demonstrated a higher pathologic response rate than those without (odds ratio [OR], 3.24 [95% CI, 1.51 to 6.94]; P = .003). In 24 ERCC2-mutant patients, the OR for pT0 was 3.33 (95% CI, 1.35 to 8.22; P = .009) and for <pT2 was 2.33 (95% CI, 0.92 to 5.89; P = .073). The association between deleterious DDR alterations and PFS provided an estimate of hazard ratio, 0.54 (95% CI, 0.29 to 1.01; P = .053). Deleterious DDR alterations were associated with pathologic response following NAC in S1314. Functional validation of ERCC2 and other DDR alterations is underway to help refine such alterations as biomarkers of NAC in patients with bladder cancer.

Tumor-Infiltrating Lymphocytes in Resected Esophageal and Gastric Adenocarcinomas Do Not Correlate with Tumor Regression Score After Neoadjuvant Chemotherapy: Results of a Case-Series Study.

Background/Objectives: Adenocarcinomas of the esophagogastric junction and stomach present clinical entities with significant cancer-related morbidity and mortality, often requiring multimodal treatments. Preoperative chemotherapy, mainly the FLOT regimen, is increasingly being utilized in the neoadjuvant setting for the treatment of these malignancies, with varying degrees of tumor response. Methods: We conducted a retrospective, single-institution review on 75 patients operated on for adenocarcinoma of the esophagogastric junction and stomach after neoadjuvant FLOT. We investigated whether tumor response correlates with disease response in lymph nodes examined on surgical specimens. We also investigated the role of tumor-infiltrating lymphocytes (TILs) in correlation with primary tumor response and disease response in lymph nodes on pathological specimens. Results: Our results suggest that TILs correlate in a differential manner with regards to primary tumors versus lymph nodes, thus suggesting that there are different biologic processes in place. Conclusions: Our results provide unique evidence on tumor-infiltrating lymphocytes in the adenocarcinoma histology of the esophagogastric junction and stomach and might be important for further studies.

Clinical factors associated with high PD-L1 expression in patients with early-stage non-small cell lung cancer.

Superior outcomes have been obtained for neoadjuvant treatment with immune checkpoint inhibitors (ICI) plus chemotherapy over neoadjuvant chemotherapy alone, especially in patients with high programmed cell death ligand 1 (PD-L1) expression. However, it is not always possible to obtain sufficient tumor specimens for biomarker testing before surgery. In this study, we explored clinical factors that can predict high PD-L1 expression. We retrospectively enrolled 340 lung cancer patients who received pulmonary resection between 2014 and 2023 and who had PD-L1 expression data. Chi-squared tests and logistic regression analyses were used to identify clinical factors associated with high PD-L1 status. Univariable and multivariable analyses revealed that smoking, high maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT), and high plasma fibrinogen are independent predictors of high PD-L1 expression. A predictive score for high PD-L1 expression (ranging from 0 to 3) was developed based on these parameters. Notably, only 5% of patients with a score of 0 exhibited high PD-L1 expression, whereas this proportion increased to 53% for patients with a score of 3. These results showed that plasma fibrinogen, smoking history, and SUVmax are predictors of high PD-L1 expression, providing a basis for identifying patients expected to benefit from neoadjuvant ICI treatment.

Correlation of intratumoral mast cell quantity with psychosocial distress in patients with pancreatic cancer: the PancStress study

Mast cells are commonly found in pancreatic ductal adenocarcinoma (PDAC), yet their role in the disease remains uncertain. Although mast cells have been associated with depression in several diseases, their connection to PDAC in this context remains unclear. This study explored the correlation between mast cells and psychosocial stress in patients with PDAC. Prior to surgery, 40 patients with PDAC (n = 29 primary resected, n = 11 neoadjuvant treated) completed four questionnaires assessing stress and quality of life. Immunostaining was performed on the resected tumor tissue. Spearman analysis was employed to correlate mast cells with distress and neuropeptides serotonin and beta-endorphin serum and tissue levels. Patients with PDAC exhibited elevated levels of distress and worry. Lower number of mast cells within the tumor correlated with greater psychological burden. Among primary resected patients, mast cell count moderately correlated with joy and inversely with worries. Following neoadjuvant chemotherapy, strong inverse correlation was observed between anxiety, depression, and mast cell quantity. No correlation was found between mast cells and serotonin or beta-endorphin levels. In summary, mast cell presence inversely correlates with psychosocial stress, suggesting a link between immune cells and psychological well-being in pancreatic cancer. Targeting mast cells might offer therapeutic avenues for addressing cancer-induced depression and anxiety.

Clinical characteristics of ovarian cancer patients with pathologic complete response after neoadjuvant chemotherapy

Clinical characteristics of ovarian cancer patients with pathologic complete response after neoadjuvant chemotherapy

Survival outcomes and potential differences in race among patients with advanced-stage endometrial cancer treated with neoadjuvant chemotherapy

Survival outcomes and potential differences in race among patients with advanced-stage endometrial cancer treated with neoadjuvant chemotherapy

Two-Year Outcomes and Biomarker Analysis of Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma After Neoadjuvant Chemotherapy and Immunotherapy from the Phase II WuhanUHGI001 Trial.

This study reports the 2-year outcomes and biomarker analysis results of patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma who received neoadjuvant chemotherapy and immunotherapy in a phase II WuhanUHGI001 trial. Eligible patients with cT3/4aN+M0 locally advanced G/GEJ adenocarcinoma were screened, enrolled, and treated with 3 cycles of neoadjuvant tislelizumab and SOX followed by D2 gastrectomy and another 5 cycles of postoperative adjuvant SOX. The primary endpoint was major pathological response. Of the 49 included patients, 24 (49.0%) achieved major pathological response and 13 (26.5%) achieved pathological complete response. During a median follow-up of 26.8 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 69.4% and 81.2%, respectively. Grade 3-4 adverse events occurred in six patients (12.2%) during the neoadjuvant period, eight patients (17.0%) during the postoperative period, and seven patients (15.2%) during the adjuvant period. Biomarker analysis revealed that the pathological complete response showed no association with 2-year PFS and OS. Major pathological response showed a potentially strong association with improved 2-year PFS and OS rates. In addition, preoperative circulating tumor cells combined with pathological responses are helpful in prognosis assessment. In addition, our results showed that T downstaging, lymphocyte-to-monocyte ratio, and CD3+ T cells were independent factors that affect PFS. The signet ring cell component (SRCC), T downstaging, and neutrophil-to-lymphocyte ratio were independent factors affecting OS. Prognostic nomograms of PFS and OS constructed based on the multivariate Cox regression results demonstrated suitable calibration and discrimination ability. Neoadjuvant tislelizumab plus SOX exhibits promising efficacy and acceptable toxicity in patients with locally advanced G/GEJ adenocarcinoma. In addition, our study established a prognostic risk signature and nomograms based on clinicopathological characteristics, which can accurately predict patient outcomes and aid in personalized treatment planning.

Results of CO2 laser surgery in laryngeal papillomatosis

Recurrent respiratory papillomatosis is medical condition strictly connected with HPV infection of the epithelium of the upper respiratory track. The main treatment of lesions located in larynx or lower pharynx includes microsurgical excision by using CO2 laser. A thorough preoperative assessment of patients is extremely important, which should not only be based on traditional laryngological examination, but also on endoscopy of the larynx and the use of the NBI (narrow band imaging) technique to assess the vascularization of lesions. In patients with recurrent papillomas, neoadjuvant therapy with antiviral agents or agents that inhibit angiogenesis is also often used. Among our group of 31 patients with laryngeal papillomas, 15 people (48%) required repeated surgical intervention and additional antiviral therapy while 10 (33%) people had to undergo the procedure three or more times due to disease recurrence. In this article we will discuss that laryngeal microsurgery with a CO2 laser is an effective method of treating patients with laryngeal papillomatosis and we will present the possibilities of adjuvant therapy.

MASSIVE GASTROINTESTINAL STROMAL TUMOR OF THE STOMACH. CLINICAL CASE

Gastrointestinal stromal tumors (GIST) are rare overall but the most common malignant mesenchymal tumors in the gastrointestinal tract. The decisive factor for the diagnosis in addition to objective symptoms is the expres­sion of the proto-oncogene KIT (CD117) receptor. The most common treatment is surgical resection, preceded by neoadjuvant therapy. In this clinical case we present a 55 year old patient’s who is diagnosed with a giant gastric GIST, effectiveness of systemic treatment.

A luminal non-coding RNA-based genomic classifier confirms favourable outcomes in patients with clinically organ-confined bladder cancer treated with radical cystectomy.

To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non-coding RNA (lncRNA)-based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. Transcriptome-wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy (n = 226). The lncRNA-based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer-specific mortality and upstaging at RC. In the study, 134 patients were clinical non-muscle-invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12-0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20-0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25-1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15-0.74; P = 0.007). This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

Significant Pathologic Response Following Neoadjuvant Therapy and Curative Resection in Patients With Rectal Cancer: Surgical and Oncological Outcomes From a Retrospective Cohort Study.

This study evaluated surgical complication rates, recurrence-free survival, overall survival (OS), and stoma status of patients with rectal cancer after significant pathologic response following neoadjuvant treatment and curative resection. Pathologic complete response (pCR) and near-pCR patients constitute patients in our study. Included was a retrospective cohort study of patients with rectal cancer who were diagnosed between July 2011 and September 2022 and who underwent neoadjuvant therapy and surgical resection. Of 696 patients with rectal cancer, 149 (21.4%) cases achieved significant pathologic response. During the 64 (70.5) months of follow-up, recurrence occurred in 16.1% of patients and distant metastases account for the majority of them. Age (p = 0.014) and receiving adjuvant chemotherapy (p = 0.016) were significantly related to the occurrence of recurrence. The five-year recurrence-free survival (RFS) and OS rates were obtained at 83% and 87%, respectively. Although age and surgical technique were significant factors in univariate Cox regression analysis, none of the candidate variables were significant prognostic factors for RFS in the multiple models. The risk of surgical complications remained in these patients. The most frequent complication attributed to infection (20.8%). Despite the 24.8% presence of permanent stoma at primary surgery, more than 50% of our patients lived without stoma at the last follow-up. Our recurrence rate was about 16%, and it was related to age and adjuvant chemotherapy. These patients achieved over 80% rates of five-year RFS and OS. No significant prognostic factors were found on RFS in the multivariable model. As a matter of course, the risk of surgical complications and permanent stoma has still remained in these patients.

Optimum radiation dose for palliation in head and neck squamous cell carcinoma (OpRAH) – A phase 3 randomized controlled trial

PurposeRadiotherapy is frequently employed for palliative treatment in locally advanced head and neck squamous cell carcinoma (HNSCC) but radiation dose fractionation regimens are not well-defined. We designed this phase 3 randomized controlled trial to compare two weekly hypo fractionated regimes and study the effect on progression-free survival (PFS) in this subset of patients. Materials and MethodsNon-metastatic locally advanced HNSCC patients (n = 305) who were not suitable for curative treatment were randomized to Arm A (20 Gy/5#/5 days) and Arm B (30 Gy/5#/5 days). PFS and OS were recorded along with acute toxicity using patient-reported quality of life HN QLQ 43. ResultsFrom April 2020 to August 2023, 390 patients were randomized, of which 305 were eligible for final analysis. At a median follow-up of 13.9 months, PFS and median overall survival (OS) for the entire cohort was 7.4 and 10.03 months, respectively. PFS (p-0.553) and OS (p-0.203) did not differ significantly between the two groups. Toxicity rates were similar between the two arms and dose escalation was well tolerated. Patients with a better PS were found to have significantly better OS. No significant benefit in OS or PFS was observed in patients who received neoadjuvant chemotherapy (NACT), underwent definitive conversion, or received palliative chemotherapy at progression. ConclusionThis is the largest phase 3 RCT to analyze the safety and efficacy of weekly palliative radiotherapy regimens and has not demonstrated further improvement with dose escalation

Neoadjuvant camrelizumab plus chemotherapy for locally advanced cervical cancer (NACI Study): A prospective, single-arm, phase II trial

Neoadjuvant camrelizumab plus chemotherapy for locally advanced cervical cancer (NACI Study): A prospective, single-arm, phase II trial

Neoadjuvant tislelizumab plus chemotherapy among patients with locally advanced cervical cancer: A prospective, single-arm, phase II trial

Neoadjuvant tislelizumab plus chemotherapy among patients with locally advanced cervical cancer: A prospective, single-arm, phase II trial

Neoadjuvant tislelizumab plus chemotherapy among patients with advanced ovarian cancer: A prospective, single-arm, phase II study

Neoadjuvant tislelizumab plus chemotherapy among patients with advanced ovarian cancer: A prospective, single-arm, phase II study

One-Stage Surgical Resection and Functional Reconstruction for Upper Limb Soft Tissue Sarcoma.

Currently, the gold standard of treatment for extremity soft tissue sarcoma (STS) is limb-sparing surgery. When the upper extremity is involved, the functional outcome is frequently poor. A 1-step resection and functional reconstruction would be advisable to obtain a fast recovery. Our study aims at retrospectively analyzing our case series of immediate nerves and tendons reconstructions of the upper limb after STS resection, while combining a review of the literature. A retrospective review was conducted on a consecutive series of patients who underwent an immediate functional reconstruction after STS resection of the upper limb between 2015 and 2022 among the IRCCS Foundation "Istituto Nazionale dei Tumori." The Disabilities of the Arm, Shoulder and Hand (DASH) score was considered the primary outcome. The obtained DASH scores were compared through groups that underwent different reconstructive procedures. The literature review was conducted according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) criteria among 3 databases (PubMed, EMBASE, and Cochrane) using the search parameters "(((upper extremity) OR (upper limb)) AND (functional reconstruction) AND (soft tissue sarcoma)." Between 2015 and 2022, 52 patients required a functional reconstruction. The mean follow-up time was 49.63 months. The DASH score analysis reported a mean value of 44.1 ± 26.7. A statistically significant difference was found between groups who underwent different reconstruction techniques, whereas no difference was found regarding exposure to neoadjuvant radiation therapy. The literature review reported few articles focusing on immediate functional reconstruction after STS resection, and only 6 articles were included in the review. Our review aimed at reporting our case series of immediate functional reconstructions after STS of the upper extremity, which is currently the most substantial one reported in literature to set an effective baseline for further studies in the field.

Poor response of HER2-positive mucinous carcinomas of breast to neoadjuvant HER2-targeted therapy: A study of four cases

BackgroundBreast mucinous carcinoma (MC) is typically positive for estrogen receptor (ER) and progesterone receptor (PR) expressions and negative for human epidermal growth factor receptor (HER2) overexpression. HER2 positive MC is a rare entity; its response to neoadjuvant HER2-targeted therapy remains unclear. MethodsFour cases of HER2 positive MC and seven cases of HER2 positive invasive ductal carcinoma with mucinous features (MCF) were identified. Clinicopathologic features were collected. Patients' germline data was gathered if available. Tumor's response to HER2-directed treatment were recorded and compared. ResultsTwo HER2 positive MCs were treated with neoadjuvant HER2-directed treatment and showed no response in the subsequent surgical resection specimens including one positive lymph node showing no treatment effect. One patient had upfront surgery. The fourth patient presented with advanced stage and showed progression on HER2-directed treatment. Six HER2 positive MCFs received neoadjuvant HER2-directed therapy; two cases showed complete pathologic response and four had only minimal residual carcinomas in the breast. Two cases with positive lymph nodes had complete response in the lymph nodes. The seventh patient presented at an advanced stage and was stable on HER2-directed treatment. ConclusionsOur findings suggest that HER2 positive MCs may be resistant to HER2-directed treatment. This is in contrast with the excellent treatment response observed in HER2 positive MCFs. It is important to report mucinous carcinoma percentage in biopsies on HER2 positive tumors as it may be related to treatment response. Further investigation of the underlying mechanisms may help optimize clinical management in this patient population.

P270 Real-world experience of neoadjuvant chemotherapy in muscle invasive bladder cancer at a university center: Role of nodal yield and prognostic value of pathological response and nutritional index

P270 Real-world experience of neoadjuvant chemotherapy in muscle invasive bladder cancer at a university center: Role of nodal yield and prognostic value of pathological response and nutritional index

P266 Impact of histological variants on the response to neoadjuvant chemotherapy in muscle-invasive urothelial bladder cancer

P266 Impact of histological variants on the response to neoadjuvant chemotherapy in muscle-invasive urothelial bladder cancer

Cancer center case volume is associated with differences in the effectiveness of neoadjuvant chemotherapy for advanced-stage epithelial ovarian cancer

Cancer center case volume is associated with differences in the effectiveness of neoadjuvant chemotherapy for advanced-stage epithelial ovarian cancer