Cycles Of Neoadjuvant Chemotherapy Research Articles

Is treatment delivery of perioperative FLOT therapy in locally advanced OGA associated with recurrence-free survival?

391 Background: Although perioperative FLOT therapy is a standard for locally advanced oesophagogastric adenocarcinoma (LA-OGA), completing all cycles, especially in the adjuvant chemotherapy (ACT) phase, is often challenging. This study examined the survival impact of treatment delivery in LA-OGA patients receiving FLOT therapy. Methods: 423 patients who underwent radical resection at The Royal Marsden Hospital from 2017 to 2023 were screened. Major inclusion criteria included patients with LA-OGA (cT2≤ and Nany or Tany and N+), treated with FLOT (at least one cycle of neoadjuvant chemotherapy) and radical resection, with an ECOG performance status of 0–2. Patients were divided into therapy incomplete (Tx Incomp, less than eight cycles of FLOT) and therapy (Tx comp) groups. We performed univariate and multivariate analyses, as well as propensity score matching (PSM) analysis, to evaluate whether treatment delivery was associated with recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier curves and restricted mean survival times (RMST) up to 36 months were used to evaluate the survival time. The primary endpoint was the 3-year RFS and OS rate. Results: Of the screened patients, 210 met the inclusion criteria, with 79 (38%) in the Tx Incomp and 131 (62%) in the Tx comp group, and 50 (24%) patients did not receive ACT. The median follow-up time was 26.5 months. The 3-year RFS and OS rates in the Tx Incomp and Tx comp groups after PSM were 54% vs 59% (p=0.14) (RMST difference: 4.04 months, p=0.09) and 58% vs 78% (p=0.04) (RMST difference: 6.15 months, p<0.001), respectively. Multivariable analysis showed a significant impact of Tx comp on OS (HR 0.53, 95% CI: 0.32-0.88). In the subgroup of ypN-positive patients, a significant difference of RMST in OS rate was observed between those who started ACT and those who did not start ACT (RMST difference: 7.89 months, p=0.01), whereas no significant difference was found in the ypN-negative group (RMST difference: 0.65 months, p=0.75). Conclusions: This study suggests that completing FLOT therapy is associated with better OS. The impact of ACT might differ according to ypN stage.

The impact of nutritional status on recurrence-free survival (RFS) in patients with locally advanced oesophagogastric adenocarcinoma (LA-OGA) treated with FLOT therapy.

388 Background: Malnutrition and weight loss were reported as poor prognostic factors in operable OGA. This study examines the relationship between oncological outcomes and nutritional status in LA-OGA patients under the current standard of care, perioperative FLOT therapy. Methods: From 2017 to 2023, 423 patients who had radical resection at Royal Marsden Hospital were screened. Inclusion criteria included LA-OGA (cT2≤ and Nany or Tany and N+), at least one cycle of neoadjuvant chemotherapy (NAC), and ECOG PS 0–2. Nutritional status was assessed by body weight and prognostic nutritional index (PNI), with significant weight loss defined as a 5% loss within six months before diagnosis or during NAC. PNI was calculated as serum albumin (g/L) + 0.005 × lymphocyte count /μL, with categories of severe (<45), mild to moderate (45–49.9), and normal (≥50). The primary endpoint was 3-year recurrence-free survival (3y-RFS). Restricted mean survival time (RMST) at 36 months was calculated to analyze survival time. Multivariate analyses were performed to identify prognostic factors for RFS. The pathological response was assessed using tumour regression grade (TRG) (Mandard criteria). Results: Of the 423 patients, 210 met the inclusion criteria. Primary tumour sites were the oesophagus (52.4%), the oesophagogastric junction (18.1%), and the stomach (29.5%). The median follow-up was 26.5 months. Weight loss at baseline and after NAC, as well as PNI, did not significantly impact RFS (p=0.13, p=0.91, p=0.69, p=0.45). However, a PNI decrease from baseline was associated with significantly shorter 3y-RFS (46% vs. 69%, p<0.001), and the RMST difference was 5.46 months (p<0.001). Multivariable analyses showed ypN positivity (p<0.001), R1 resection (p<0.001), and PNI decrease (p=0.03) as negative prognostic factors for RFS. Pathological response did not differ regardless of PNI change (28.2% vs. 30.4%, p=0.75). Conclusions: A decrease of PNI is a significant poor prognostic factor for RFS in LA-OGA patients undergoing FLOT, suggesting that maintaining nutritional status during NAC could enhance survival outcomes.

Neoadjuvant chemotherapy with FOLFOXIRI for high-risk relapsed locally advanced colon cancer: A single-arm phase II trial.

201 Background: To evaluate the safety and efficacy of neoadjuvant chemotherapy (NAC) with three drug-intensity chemotherapy (oxaliplatin, irinotecan, and fluorouracil [FOLFOXIRI]) in patients with high-risk factors for recurrence and metastasis of locally advanced colon cancer (hr-LACC). Methods: A single-arm, open-label, phase II trial was conducted at West China Hospital of Sichuan University from July 2020 to Oct 2023. Patients with T4a/b or (and) N2/fused lymph nodes) and no distant metastases were considered as the hr-LACC patients. Eligible enrolled patients received four cycles of NAC with FOLFOXIRI followed by surgery and adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) for two to five cycles or single-agent capecitabine for five cycles or observation. The primary endpoint was the rate of TRG grade 0-2 according to the criteria of NCCN guideline. Results: Of 72 patients enrolled (median age 53 [18-74] years,65 were T4a/b [90.2%], 66 were N2 [91.6%]), 58 patients (80.6%) completed four cycles of FOLFOXIRI. Three patients (4.2%) achieved clinical complete response. Twenty-eight patients (39.4%) obtained clinical partial response. The most common adverse event (AE) was nausea (86.1%, 62/72); grade 3-4 AEs occurred in 37 of 72 patients (51.4%).R0 resection was achieved in 64 of 64 patients, and the TRG (0-2) rate was 87.5% (56/64). The pathologic complete response rate was 7.8% (5/64). The proportions of pT0-2 and pN0 were 21.9% and 68.8%, respectively. Only three (4.7%) patients had prolonged hospital stay due to perioperative complications. No patient died within 30 days and 90 days after surgery. The 2-year tumor recurrence rate was 17.2%. Conclusions: For patients with hr-LACC, NAC with FOLFOXIRI regimen was safe and effective. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. Clinical trial information: NCT05018182 .

A deep learning approach for early prediction of breast cancer neoadjuvant chemotherapy response on multistage bimodal ultrasound images

Neoadjuvant chemotherapy (NAC) is a systemic and systematic chemotherapy regimen for breast cancer patients before surgery. However, NAC is not effective for everyone, and the process is excruciating. Therefore, accurate early prediction of the efficacy of NAC is essential for the clinical diagnosis and treatment of patients. In this study, a novel convolutional neural network model with bimodal layer-wise feature fusion module (BLFFM) and temporal hybrid attention module (THAM) is proposed, which uses multistage bimodal ultrasound images as input for early prediction of the efficacy of neoadjuvant chemotherapy in locally advanced breast cancer (LABC) patients. The BLFFM can effectively mine the highly complex correlation and complementary feature information between gray-scale ultrasound (GUS) and color Doppler blood flow imaging (CDFI). The THAM is able to focus on key features of lesion progression before and after one cycle of NAC. The GUS and CDFI videos of 101 patients collected from cooperative medical institutions were preprocessed to obtain 3000 sets of multistage bimodal ultrasound image combinations for experiments. The experimental results show that the proposed model is effective and outperforms the compared models. The code will be published on the https://github.com/jinzhuwei/BLTA-CNN.

Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: ASCO Guideline Update.

To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]). A multidisciplinary Expert Panel convened and updated the systematic review. Sixty-one studies form the evidence base. Patients with suspected stage III-IV EOC should be evaluated by a gynecologic oncologist, with cancer antigen 125, computed tomography of the abdomen and pelvis, and chest imaging included. All patients with EOC should be offered germline genetic and somatic testing at diagnosis. For patients with newly diagnosed advanced EOC who are fit for surgery and have a high likelihood of achieving complete cytoreduction, PCS is recommended. For patients fit for PCS but deemed unlikely to have complete cytoreduction, NACT is recommended. Patients with newly diagnosed advanced EOC and a high perioperative risk profile should receive NACT. Before NACT, patients should have histologic confirmation of invasive ovarian cancer. For NACT, a platinum-taxane doublet is recommended. Interval cytoreductive surgery (ICS) should be performed after ≤four cycles of NACT for patients with a response to chemotherapy or stable disease. For patients with stage III disease, good performance status, and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy may be offered during ICS. After ICS, chemotherapy should continue to complete a six-cycle treatment plan with the optional addition of bevacizumab. Patients with EOC should be offered US Food and Drug Administration-approved maintenance treatments. Patients with progressive disease on NACT should have diagnosis reconfirmed via tissue biopsy. Patients without previous comprehensive genetic or molecular profiling should be offered testing. Treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care.Additional information is available at www.asco.org/gynecologic-cancer-guidelines.This guideline has been endorsed by the Society of Gynecologic Oncology.

Prognostic Value of POST-Treatment Extent of Tumor (POSTTEXT) System in Patients with Hepatoblastoma.

To assess prognostic values of the POST-Treatment Extent of Tumor (POSTTEXT) system and clinical factors after neoadjuvant chemotherapy in hepatoblastoma patients and evaluate benefits of posttreatment imaging and clinical factors concomitant with Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system. This single-center retrospective study of hepatoblastoma cases (2006-2022) included pediatric patients receiving ≥ 4 cycles of neoadjuvant chemotherapy, with pre- and post-treatment imaging and complete medical records. Clinical data included age, sex, and serum alpha-fetoprotein (AFP) levels. Cox regression analyses identified predictors of event-free survival (EFS). Time-dependent receiver operating characteristic curves assessed the predictive power of combining the CHIC-HS risk stratification with posttreatment factors. Inter-reader agreement was analyzed using weighted kappa. Among the 109 hepatoblastoma patients, 73 (mean age: 2.2 ± 2.7 years) met the inclusion criteria. Prognostic factors for EFS included AFP levels after the fourth cycle of neoadjuvant chemotherapy (HR, 1.233; 95% CI, 1.806-1.400; p=0.001), tumor size change ratio (HR, 0.654; 95% CI, 0.448-0.955; p=0.03), and POSTTEXT annotation factor M (HR, 5.209; 95% CI, 1.639-16.553; p=0.005). Incorporating AFP levels after the fourth cycle of neoadjuvant chemotherapy into the CHIC-HS improved predictive power (p=0.043). POSTTEXT system showed better inter-reader agreement than PRETEXT. Predictors of EFS in hepatoblastoma include AFP levels after the fourth cycle of neoadjuvant chemotherapy, tumor size change ratio, and metastasis (POSTTEXT M). Combining AFP levels after the fourth cycle of neoadjuvant chemotherapy to the CHIC-HS improved the predictive ability.

Value of [18F]AlF-NOTA-FAPI-04 PET/CT for predicting pathological response and survival in patients with locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant chemotherapy.

This study aimed to evaluate the predictive value of [18F]AlF-NOTA-FAPI-04 PET/CT for pathological response to neoadjuvant chemotherapy (NCT) and prognosis in patients with locally advanced pancreatic ductal adenocarcinoma (LAPDAC). This study included 34 patients with histopathologically and radiologically confirmed LAPDAC who received [18F]AlF-NOTA-FAPI-04 PET/CT scans before NCT. After 4-6 cycles of NCT, these patients underwent radical resection. Pathological response to NCT was assessed by pathological tumor regression grades (TRG) based on the Evans system. PET/CT parameters were evaluated for their association with TRG, recurrence-free survival (RFS) and overall survival (OS) after NCT, including the maximum standardized uptake value (SUVmax), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) of primary tumor, total FAPI-avid pancreatic volume (FPV) and total pancreatic FAP expression (TPF) of total pancreas. Of 34 patients with LAPDAC, 14 patients had a pathologic good response (PGR, Evans III-IV), and 20 patients had a pathologic poor response (PPR, Evans I-II). Both the primary tumor SUVmax, FTV and TLF, and total pancreas FPV and TPF in the PGR groups were significantly lower than those in the PPR groups. Furthermore, SUVmax and TLF were higher in poorly differentiated LAPDAC than in well-moderately differentiated neoplasms. The FTV, TLF, FPV and TPF were closely associated with RFS and OS. On multivariate analysis, patients with FTV > 54.21 and TLF > 290.21 had a worse RFS and OS, respectively (HR = 3.24, P = 0.014 and HR = 3.35, P = 0.019) and OS (HR = 7.35, P = 0.002 and HR = 7.09, P = 0.004) in LAPDAC after NCT. The parameters of [18F]AlF-NOTA-FAPI-04 PET/CT had the excellent performance for predicting pathologic TRG after NCT in LAPDAC. FTV and TLF were independent postoperative prognostic factors for RFS and OS for LAPDAC.

Efficacy of Neoadjuvant Chemotherapy as pre-habilitation program in advanced epithelial ovarian cancer.

Approximately 70% of ovarian cancer patients present at diagnosis with advanced disease(AOC) and impaired clinical conditions, making them not ideal surgical candidates. We aimed to investigate whether neoadjuvant chemotherapy(NACT) can modify pre-operative characteristics of patients at high risk(HR) of perioperative complications, as defined in the Mayo Clinic Algorithm. We also compared their morbidity and survival outcomes with comparable HR women undergoing primary surgery (PCS). We retrospectively collected FIGO stage III and greater AOC patients undergoing either NACT-interval cytoreductive surgery(HR-NACT) or PCS from 01/2013 to 12/2022. HR features included: Albumin <3.5g/dL or age≥80 years or age 75-79 and at least one among: ECOG PS>1, stage IV disease, or complex surgery likely (more than hysterectomy, salpingo-oophorectomy and omentectomy). 400 patients were included. Among them, 298 met the criteria for the HR-NACT group; 203(68.1%) underwent ICS after 3-4 cycles whislt 95(31.9%) completed 6 NACT cycles. We reported an improvement in clinical variables in women undergoing 3-4 cycles of NACT: raise of ECOG=0 rate(53.3% vs 81.8%; p<0.001) and median albumin serum levels(3.0g/dl vs 4.0g/dl; p<0.001). We identified 102 comparable HR-PCS patients. No difference in intraoperative complications was detected, while a difference was found in severe post-operative complications, favoring patients treated with both 3-4(5.4% vs 18.6% p=0.0003) and 6 NACT cycles(7.8% vs 18.6%, p=0.053). No difference in both DFS and OS was reported. We offer a rationale to combine non interventional pre-habilitation procedure with short term chemotherapy cycles, aiming to improve pre-operative conditions of selected HR patients.

Neoadjuvant Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Chemotherapy for Muscle-Invasive Urothelial Cancer: Large, Single-Center Analysis of Consecutive Patients' Data.

Background/Objectives: Bladder cancer is a significant clinical problem with approximately 500,000 new cases worldwide annually. In approximately 25% of cases, disease is diagnosed at a stage of invasion of the muscle layer of the bladder. The current standard approach in this disease is preoperative chemotherapy followed by radical cystectomy. Dose-dense MVAC (ddMVAC), a two-day chemotherapy regimen, is the reference treatment protocol in this setting. The presented study evaluated the effectiveness and safety of accelerated MVAC (aMVAC) chemotherapy-a one-day regimen given before the resection of the bladder due to muscle-invasive disease. Methods: A retrospective analysis included 119 consecutive patients diagnosed with urothelial muscle-invasive bladder cancer (MIBC) who underwent preoperative chemotherapy with the aMVAC regimen. The planned treatment included 4-6 cycles of preoperative chemotherapy. The analysis of the degree of histopathological response to treatment was based on the three-grade TRG (tumor regression grade) classification. Results: A complete pathological response (TRG1) was observed in 44 patients (36.7%), and a major pathologic response (<ypT2) was achieved in 58 patients (48.7%). A reduction in the cisplatin dose was associated with a statistically significant decrease in the chance of achieving complete pathologic responses (46.1% vs. 10%, RR for TRG1 = 0.69, p = 0.00118). Patients who received at least 4 cycles (compared to ≤3 cycles) of neoadjuvant chemotherapy had a significantly higher chance of achieving a pathological response (partial or complete) to treatment (78.1% vs. 52.2%, RR 0.68, p = 0.0374). Administration of at least five cycles of chemotherapy was associated (compared to four cycles) with a significantly higher likelihood of achieving a complete pathological response (63.2% vs. 33.8%, RR = 1.71, p = 0.0221). The vast majority of adverse events were in grades 1 and 2, according to CTCAE version 5.0. Only five patients experienced grade 3-4 toxicities. The most common adverse event was anemia, which occurred in 66.3% of patients. Conclusions: Our real-world data analysis confirms the activity, safety, and feasibility of the aMVAC regimen as neoadjuvant chemotherapy in patients with urothelial MIBC.

Impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period

AIM: assess the impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period.PATIENTS AND METHODS: a pilot prospective study included 30 patients with colorectal cancer and synchronous liver metastases (mCRC). The combined treatment included 3 cycles of neoadjuvant FOLFOXIRI chemotherapy with the addition of targeted agents: cetuximab (24 patients with wtKRAS) and bevacizumab (6 patients with mtKRAS) followed by radical surgery.RESULTS: the clinical and radiological response of colorectal cancer liver metastases to neoadjuvant chemotherapy (NACT) was complete in 4 (13.3%) patients and partial in 26 (86.7%) patients. Partial response to NACT in the primary tumor occurred in all patients. Adverse events of NACT were detected in 12 (40%) patients, 1 (3.3%) of them produced grade III toxicity. All patients underwent radical surgery (R0) 3–4 weeks after NACT, 28 (93.3%) of them underwent simultaneous colorectal and liver resection. Postoperative complications occurred in 21 (70%) patients, including grade I and grade IIIa complications (according to Сlavien-Dindo classification) — 22 (73.3%) and 2 (6.7%), respectively. Histology revealed pathologic complete response (pCR) of liver metastases in 1 (3.6%) case and pathological grade 3 regression of the primary tumor (TRG3, Mandard A.M.) in 23 (76.7%) patients. Two (6.7%) patients with complete clinical and radiological response of liver metastases, who did not undergo liver resection, had no evidence of disease progression 12 months after the treatment.CONCLUSION: in mCRC with synchronous liver metastases, NACT according to the FOLFOXIRI regimen in combination with targeted agents with a moderate toxicity profile provide significant carcinocidal effect without having a negative impact in the perioperative period. The study is ongoing to analyze 2-year disease-free and overall survival of patients.

Prognostic value of circulating tumor DNA at diagnosis and its early decrease after one cycle of neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer. An ancillary analysis of the CHIVA phase II GINECO trial.

To evaluate the prognostic impact of circulating tumor DNA (ctDNA) detection at diagnosis (T0) and its early decrease after one cycle (T1) of neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC) included in the CHIVA trial (NCT01583322). Blood samples were collected at T0 and before each administration of NACT. Circulating tumor DNA detection was performed by next-generation sequencing. Multivariate analysis was performed. A p-value of 0.05 was considered significant. Progression-free survival (PFS) and overall survival (OS) were compared between groups defined by ctDNA kinetic profile. Cox survival model was used to search variables associated with PFS and OS. Kaplan-Mayer curve was used to graphically express the differences in PFS and OS. A log-rank test compared the two curves. 188 patients were included. Blood samples were available for 168 patients at T0 and for 160 patients at T0 and T1 to assess ctDNA ratio kinetics. At T0, 107 patients (63.7%) had detectable ctDNA. At T1, 137 (85.6%) patients had negative ctDNA or a decrease of more than 80%. There was a significant benefit in either PFS (p=0.0017) or OS (p=0.0036) in favor of early decrease of ctDNA ratio. A favorable decrease was associated with a greater likelihood of being able to perform CRS (OR: 3.94 (CI95% 1.45-10.70), p=0.0074). Early decrease of ctDNA ratio can provide prognostic information early in the management of patients, allowing a more accurate information to patients and an early preparation for CRS (prehabilitation).

Perioperative tislelizumab with four cycles of neoadjuvant chemotherapy for resectable locally advanced esophageal squamous cell carcinoma: a phase 2 study.

The application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC). In this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy. The study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte. The combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC. https://www.chictr.org.cn/, identifier ChiCTR2100043772.

Model based on ultrasound and clinicopathological characteristics for early prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer.

Accurate assessment of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is crucial for mitigating chemotherapy-related toxicity in patients who do not respond to the treatment. Conventional ultrasound (US) has become a pivotal method for evaluating treatment response due to its cost-effectiveness, convenience, and absence of ionizing radiation. The objective of this study was to develop a model combining US and clinicopathological characteristics at baseline, as well as US features after one cycle of NAC, to predict the pCR to NAC in BC. This retrospective study included 74 patients with invasive BC who underwent NAC from January 2022 to December 2023. Data from US and clinicopathological characteristics before NAC (pre-NAC) and US features after one cycle of NAC were collected from all patients. Univariate and multivariate analyses were used to screen the factors independently associated with pCR and to develop the prediction model. Receiver operating characteristic (ROC) curve analysis was performed, and the area under the curve (AUC), sensitivity, and specificity were calculated to assess the predictive efficiency. Four characteristics, including human epidermal growth factor receptor 2 (HER2)-positive [odds ratio (OR) 9.265; 95% confidence interval (CI): 1.617-53.095, P=0.012] and absence of posterior feature or posterior acoustic enhancement of the breast mass on the US pre-NAC (OR 9.435; 95% CI: 1.585-56.180, P=0.014), the maximum diameter reduction measured with the US (OR 1.081; 95% CI: 1.009-1.157, P=0.026), and the angular or spiculated margin of the breast lesion with the US after one cycle of NAC (OR 9.475; 95% CI: 1.247-71.969, P=0.030), were screened as independent predictors. The AUC, sensitivity, and specificity of the prediction model were 0.912, 90.0%, and 79.6%, respectively. US and clinicopathological characteristics at baseline and the US features after one cycle of NAC helped predict pCR for BC. The prediction model may enable early evaluation of the efficacy of treatment strategies and guide less invasive surgical options or personalized post-treatment plans.

The predictive role of PD-L1 expression and CD8 + TIL levels in determining the neoadjuvant chemotherapy response in advanced ovarian cancer

ObjectiveTo analyze how the PD-L1 expression and CD8 + tumor infiltrating lymphocyte (TIL) levels in biopsy samples before neoadjuvant chemotherapy (NACT) can predict chemotherapy response score and survival for advanced high-grade serous ovarian cancer (HGSC).MethodsWe retrospectively analyzed 45 patients with advanced epithelial ovarian cancer between 2010 and 2018, who had received at least three cycles of NACT. PD-L1 expression and CD8 + TIL levels were evaluated by immunohistochemical staining in the pre-NAC tumor samples from which the patients had been diagnosed. The post-NACT tissue samples taken during interval debulking surgery (IDS) were used to evaluate the chemotherapy response score (CRS).ResultsAmong all the patients, CRS 1 (no response) was found in 8 patients, CRS 2 (partial response) in 28 patients, and CRS 3 (complete response) in 9 patients. A total of 20 (44.4%) patients had high intratumoral CD8 + TILs (iCD8 + TILs) levels, and 35 (77.8%) patients had high expression stromal CD8 + TILs (sCD8 + TILs). No statistically significant relationship was found between high and low expression of i/s CD8 + TILs levels with PFS and CRS. The study found that 33 (73.3%) patients had high levels of stromal PD-L1 (sPD-L1) expression and 28 (62.2%) patients had high levels of intratumoral PD-L1 (iPD-L1) expression. In the iPD-L1 group, patients with low expression had a PFS of 28 months, whereas those with high expression had a PFS of 17 months (p = 0.028). Among the patients with high iPD-L1 expression, 23 (82.1%) patients showed CRS2, 4 (14.3%) showed CRS3, and only 1 (3.6%) showed CRS1 (p < 0.001). However, high or low expression sPD-L1 did not significantly affect PFS and CRS (p = 0.928 and p = 0.305; respectively).ConclusionsWe found that iPD-L1 expression levels in diagnostic biopsy in ovarian cancer can predict the chemotherapy response score in interval debulking surgery.

MR tomographic evaluation of the effectiveness of neoadjuvant chemotherapy for breast cancer based on pharmacokinetic numerical analysis of tumor uptake of paramagnetic contrast in intravenous contrast enhancement

Background. In clinical practice, MRI pathophysiological and pharmacokinetic models with calculations of contrast transport indicators are unacceptably little used.Aim of the study. To propose a pharmacokinetic technique for the quantitative assessment of primary tumors and metastases, the effectiveness of breast cancer chemotherapy (BC), from dynamic contrast enhancement MRI. Material and methods. 18 patients were included who underwent neoadjuvant chemotherapy (NACHT) in four cycles for breast cancer T1-3N0-1M0, followed by radical surgical removal of the tumor. According to the results of a three — year follow-up, patients with a relapse — free course (n = 11) formed group 1, and seven patients with detected metastatic lesions (3 in the liver, 2 in the lungs, 2 in the brain) — group 2. For the initial 120–180 s of MRI with contrast after the injection of a paramagnetic, the simplification is valid for concentrations in tumor and blood and for tranfer coefficient: d{СОПУХОЛЬ(t)} / dt = ККр-Оп * СКРОВЬ (t) , from which it is obvious: ККр-Оп = (СОПУХОЛЬ(Т)) / (∫CКРОВЬ(t) dt), which was used in all calculations of the contrast transfer constant. Gadobutrol contrast is 0.1M/10 kg of body weight, TR = 5.5–6 ms, TE = 2.5 ms. Results. If, after the first cycle of NACHT, the ККр-Оп of the primary breast cancer is &lt; 0.22 ml/min/g of tissue, the probability of subsequent relapse-free course = 0.78. Similarly, a decrease in the KCr-Op Ккр-Оп of the sentinel lymph node after the first cycle of NAHT &lt; 0.08 ml/min/g of tissue with a probability of 0.75 predicts a relapse-free course. Conclusion. The proposed method for calculating the ККр-Оп transfer coefficient allows obtaining additional diagnostic and prognostic information in patients with local and locally advanced forms of breast cancer.

Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy in High-Grade Epithelial Ovarian Cancer

Despite the absence of high-quality evidence of its safety and effectiveness, minimally invasive surgery (MIS) is increasingly used to treat advanced epithelial ovarian cancer (EOC). To assess the feasibility of conducting a full-scale randomized clinical trial (RCT) designed to compare the efficacy of MIS vs laparotomy in patients with advanced-stage EOC and a complete or partial response to neoadjuvant chemotherapy (NACT). This lead-in pilot phase of LANCE (Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy), an international, open-label, noninferiority RCT, opened to enrollment in September 2020 and enrolled the 100th eligible patient in February 2023. It was conducted at 11 academic cancer centers in North America and Europe. Participants were adults with stage IIIC or IV epithelial ovarian, fallopian, or primary peritoneal carcinoma who had normal cancer antigen 125 levels and at least a partial radiologic response after 3 to 4 cycles of NACT. Patients were randomly assigned to receive either interval cytoreductive surgery performed using MIS or laparotomy. Data analysis was based on the evaluable population. The MIS arm underwent laparoscopic or robotic surgery, vs laparotomy for the control arm. Resection of all visible tumor was attempted, and conversion from MIS to laparotomy was performed when necessary to attain complete resection. Trial feasibility was defined by 3 primary end points: patient accrual rate of at least 5.6 patients per month by the last month of the lead-in pilot phase, conversion from MIS to laparotomy in less than 25% of patients, and a difference in complete gross resection rates of fewer than 20 percentage points between study arms. One hundred women (median [IQR] age, 63 [39-82] years) were included, of whom 49 were randomly assigned to MIS and 51 to laparotomy; 95 were evaluable for surgical outcomes. Most patients (34 [67%] in the laparotomy arm, and 33 [67%] in the MIS arm) had stage IIIC cancer. The monthly accrual rate reached 5.9 patients per month in the final month of the study. Six of 48 evaluable patients (12.5%; 95% CI, 4.7%-25.2%) assigned to MIS underwent conversion to laparotomy. Surgeons achieved a complete gross resection rate in 42 of 48 evaluable patients (88%) assigned to MIS and in 39 of 47 patients (83%) assigned to laparotomy (difference, 4.5 [95% CI, -9.7 to 18.8] percentage points). Results of this lead-in pilot study indicated the feasibility of the LANCE RCT to compare the oncological outcomes of MIS vs laparotomy. ClinicalTrials.gov Identifier: NCT04575935.

Intraoperative imaging of residual ovarian cancer after neoadjuvant chemotherapy using indocyanine green

ObjectivesInterval debulking surgery has similar outcomes and less morbidity compared with primary debulking in advanced ovarian cancer. However, there is controversy regarding the selection of chemotherapy-resistant clones. Complete resection is...

Downstaging Effect Rather than the Full Intended Cycles of Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

Perioperative chemotherapy is the standard treatment modality for locally advanced gastric cancer. However, the efficacy and indication of adjuvant chemotherapy in patients who have already received neoadjuvant chemotherapy remain unclear. This study aims to explore the association between adjuvant chemotherapy with patient prognosis in those who have received neoadjuvant chemotherapy plus D2 gastrectomy in a real-world setting, and whether this association is affected by the duration of neoadjuvant treatment. A total of 174 patients with cT3-4N+ gastric cancer who had received neoadjuvant chemotherapy plus D2 radical gastrectomy were included in the study. Kaplan-Meier curves and log-rank tests were used to assess and compare the survival outcomes between patients who received adjuvant therapy and those who did not. Patients who were younger age, had a lower American Society of Anesthesiologists (ASA) grade, did not experience postoperative complication, and received fewer than six cycles of neoadjuvant chemotherapy were more likely to receive adjuvant chemotherapy, rather than those with advanced ypTNM stage or poor tumor regression grade. Patients who received adjuvant therapy had a better overall survival (OS) (2-year OS rate 86.2% versus 64.1%, p=0.002). Adjuvant therapy was associated with longer survival in patients who remained ypTNM stage III despite receiving at least six cycles of neoadjuvant chemotherapy. However, there was no significant longer survival observed in patients with ypTNM stages 0-II receiving adjuvant chemotherapy, even when they received less than six cycles of neoadjuvant chemotherapy. Patients with locally advanced gastric cancer may still need adjuvant chemotherapy, even after receiving neoadjuvant chemotherapy. The value of adjuvant chemotherapy after neoadjuvant chemotherapy depends more on the actual downstaging effect achieved after neoadjuvant chemotherapy, rather than the completion of "full intended" cycles of perioperative treatment.

Preventive efficacy of hydrocortisone enema for radiation proctitis in rectal cancer patients undergoing short-course radiotherapy: a phase II randomized placebo-controlled clinical trial.

This study aimed to investigate the efficacy of hydrocortisone enema in preventing radiation proctitis in patients with rectal cancer undergoing short-course radiotherapy (SCRT). This phase II randomized controlled trial enrolled patients with newly diagnosed locally advanced rectal cancer (clinically staged T3-4 and/or N1-2M0). Participants received a median of 4 cycles of neoadjuvant chemotherapy (capecitabine plus oxaliplatin) followed by 3-dimensional conformal SCRT (25 Gy in 5 fractions). Patients were randomly assigned to receive either a hydrocortisone enema (n=50) or a placebo (n=51) once daily for 5 consecutive days during SCRT. The primary endpoint was the incidence and severity of acute proctitis. Of the 111 eligible patients, 101 were included in the study. Baseline characteristics, including sex, age, performance status, and tumor location, were comparable across the treatment arms. None of the patients experienced grade 4 acute gastrointestinal toxicity or had to discontinue treatment due to treatment-related adverse effects. Patients in the hydrocortisone arm experienced significantly less severe proctitis (P<0.001), diarrhea (P=0.023), and rectal pain (P<0.001) than those in the placebo arm. Additionally, the duration of acute gastrointestinal toxicity following SCRT was significantly shorter in patients receiving hydrocortisone (P<0.001). Hydrocortisone enema was associated with a significant reduction in the severity of proctitis, diarrhea, and rectal pain compared to placebo. Additionally, patients treated with hydrocortisone experienced shorter durations of gastrointestinal toxicity following SCRT. This study highlights the potential benefits of hydrocortisone enema in managing radiation-induced toxicity in rectal cancer patients undergoing radiotherapy.

Feasibility of neoadjuvant chemotherapy for bulky early stage to stage IIIB cervical cancer in Uganda

IntroductionExternal beam radiotherapy (EBRT) became unavailable in Uganda from February 2016 to November 2017. Following resource stratification guidelines, an alternative treatment strategy was developed. MethodsBulky early stage to Stage IIIB patients received at least 3 cycles of neoadjuvant chemotherapy (NAC). Surgery was performed if adequate response was achieved and adjuvant therapy given for high risk factors. Chemotherapy versus supportive care was advised in unresectable disease. NAC protocol completion was defined as receiving at least 3 cycles of NAC followed by either surgery, chemotherapy and/or radiation, or best supportive care. The purpose of this study was to determine the completion rate of NAC and assess the adverse events associated with treatment. Data were collected through retrospective chart review. ResultsFrom February 2016 to November 2018, 53 evaluable patients were identified. 86.8% (46/53) of patients presented in Stage IIB or higher. The completion rate of the NAC protocol was 75.5% (40/53). 94.3% (50/53) received platinum-taxane combination. 7.6% (4/52) grade 3 adverse events occurred related to chemotherapy, all hematologic. 18.8% (10/53) patients underwent surgery with 2 aborted cases due to metastatic or inoperable disease. No adverse events related to surgery were reported. 5 patients underwent adjuvant therapy after surgery due to high risk factors or incomplete pathology findings. 26 patients received adjuvant radiation (3 brachytherapy, 23 EBRT after it became available). Reported side effects related to radiation included vaginal fibrosis and skin reactions. ConclusionIn this limited-resource setting, majority of patients completed a NAC treatment strategy for cervical cancer with acceptable toxicities.