Neoadjuvant Treatment Research Articles (Page 4)

The optimal management of oestrogen receptor (ER)-low HER2-negative breast cancer (BC) is unclear. We surveyed current approaches of UK clinicians in ER-low BC, and also present outcomes of ER-low early BC at single centre. Survey: We conducted an anonymised online survey of clinicians treating BC in the UK between 6May and 5June 2024. Participants were presented with clinical scenarios of ER-low (Allred ER3/ER4) BC with multiple-choice and free-text questions. Clinical audit: Patients diagnosed with stageI-III, ER2-4 HER2-negative BC undergoing neoadjuvant treatment (chemotherapy vs. chemo-immunotherapy) from 1January 2017 to 31December 2023 were included. Clinical data was collected retrospectively at Barts Health NHS Trust, London, UK. The primary endpoint was pathological complete response (pCR). Survey: Of 72 survey respondents, 40% recommended neoadjuvant chemo-immunotherapy for ER3 disease vs. 10% for ER4 disease; 57% recommended adjuvant endocrine therapy for ER3 disease, and 90% for ER4 disease. In the advanced setting 75% recommended chemo-immunotherapy for PD-L1-positive ER3 disease with 7% recommending CDK4/6 inhibitors. For PDL1-positive ER4 disease, these percentages were 32% and 51% respectively. In PDL1-negative disease, chemotherapy rates were 81% for ER3 and 36% for ER4 disease. Clinical audit: Sixty-six patients receiving neoadjuvant treatment were included, with 29 belonging to the ER2, 30 belonging to the ER3 and 7 belonging to the ER4 groups respectively; 33% received neoadjuvant chemo-immunotherapy. pCR rate was 61%, with no association with ER score for chemotherapy (p = 0.319) and chemo-immunotherapy (p = 0.603). There is marked variation in approach to ER-low in the UK. The audit data suggests treating ER-low BC as triple-negative BC.

Rectal cancer has become a significant health concern in current years, but there are very effective current neo-adjuvant treatment modalities which can result in the complete disappearance of the disease without surgery, which is often associated with severe post-surgical sequelae. Therefore, a significant effort has been made to identify the subset of patients who can avoid surgery and to investigate the long-term oncologic and functional results associated with the Non-Operative Management of such a disease.

Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary.

Simple SummaryProstate cancer is the second most common malignancy among men, and the number of new cases is projected to increase substantially in the coming years. To assess the current state of knowledge on the economic burden of this disease, we conducted a literature review that included 31 studies. Our analysis focused on estimates of direct costs—such as treatment, adjuvant and neoadjuvant therapies, and supportive and palliative care—as well as indirect costs. However, the vast majority of studies addressed direct costs only, highlighting a clear gap in the literature. This accentuates the need for further comprehensive reviews and the development of standardized methodologies to enable reliable comparisons across studies.Background: Prostate cancer is the second most common malignant cancer among men, and according to the predictions, the estimated number of new cases will substantially grow in the coming years. Therefore, the costs of the disease will increase as well. Methods: We conducted a literature review of the state of knowledge about the costs of treatment and the economic burden of prostate cancer. The vast majority of studies were focused on direct costs only, which clearly shows the literature gap. Results: We focused on the estimates of direct costs, i.e., treatment of prostate cancer, adjuvant and neoadjuvant treatment, and supportive and palliative care, and indirect costs. Cost-effectiveness analyses indicated that docetaxel combined with androgen deprivation therapy (ADT) was the most cost-effective strategy for metastatic hormone-sensitive prostate cancer (incremental cost-effectiveness ratio (ICER): USD 13,647). In contrast, novel therapies such as PARP inhibitors and whole-genome-sequencing-guided treatments were not cost-effective unless drug prices were reduced by 47–70%. In the United States, 5-year cumulative treatment costs ranged from USD 48,000 for conservative management to over USD 91,000 for radiotherapy, while out-of-pocket expenses averaged AUD 1172 in Australia. Indirect costs were also considerable, with Slovakia reporting an increase in sick leave costs from EUR 1.2 million in 2014 to EUR 2.1 million in 2022. Conclusions: Metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer were the most frequent categories for various treatment cost evaluations. A few specific combinations of drugs were cost-effective only under the condition of dropping the unit prices of a medication. Further summarizing, reviewing, and developing a methodology for standardized comparisons are needed.

Treatment paradigms for patients with locally recurrent rectal cancer (LRRC) have shifted from palliative approaches to multimodal curative-intent treatment in selected patients. This retrospective cohort study evaluates survival outcomes following curative-intent treatment in patients with LRRC. All consecutive patients with LRRC undergoing curative-intent treatment at a tertiary referral center between 2014 and 2024 were retrospectively analyzed (n=147). Overall survival (OS), local re-recurrence-free survival (LRFS), metastasis-free survival (MFS), and prognostic factors were analyzed using Kaplan-Meier and Cox regression analyses. 147 patients underwent neoadjuvant treatment with curative intent at baseline. After response assessment, 117/147 (80%) patients continued curative therapy, which consisted of 109/117 (93%) patients undergoing surgery and a highly selected group of 8/117 (7%) patients monitored with a watch-and-wait strategy. For the remaining 30/147 patients (20%), treatment intent changed from curative to palliative. Median OS was 54months with a 5-year OS of 47%. For patients treated with an overall curative intent (n=117), median OS was 63months with a 5-year OS of 58%. Clear resection margins, achieved in 76% of surgical cases, was a prognostic factor for OS and LRFS: 5-year OS was 66% for R0-resections and 33% for R1-resections (p<0.001), and 3-year RFS was 69% for R0-resections and 50% for R1-resections (p<0.001). Among the watch-and-wait group, 5/8 patients remained alive and disease-free (median follow-up 14months (IQR 9-16)). This single-center retrospective cohort study demonstrates reasonably good oncological outcomes following curative-intent LRRC treatment. Further investigation of watch-and-wait strategies in highly selected patients is warranted.

Abstract Purpose: Exploratory data suggest a benefit of an immune checkpoint inhibitor (ICI) monotherapy window in early triple-negative breast cancer (TNBC). The neoMono trial prospectively investigated whether the addition of an atezolizumab monotherapy window before neoadjuvant atezolizumab and chemotherapy improves pathologic complete remission (pCR) rates in early TNBC. Patients and Methods: neoMono is a phase 2 randomized multicenter trial that recruited patients with primary TNBC larger than 10 mm. Neoadjuvant treatment in both arms consisted of neoadjuvant atezolizumab and chemotherapy, with treatment in arm A preceded by atezolizumab monotherapy 2 weeks before combination therapy. This study used a Bayesian trial design. Results: A total of 359 patients were included. Overall, pCR rates in study arms A and B were similar (intention-to-treat population: 65.7% and 69.0%, respectively). In an exploratory analysis, pCR rates in PD-L1–positive tumors were 91.5% in arm A and 82.2% in arm B. The corresponding pCR rates in the PD-L1–negative group were 56.1% in arm A and 64.5% in arm B. In patients with low-risk TNBC (cT1c and cN0), pCR rates in the PD-L1–positive group were 100.0% in arm A and 90.0% in arm B, and the corresponding pCR rates in the PD-L1 (immune cell)–negative group were 65.9% and 76.3%, respectively. Conclusions: The neoMono trial demonstrated the highest pCR rates reported in a phase II/III trial in TNBC, particularly in the case of PD-L1 positivity. Although no significant impact of an ICI monotherapy window on the pCR rate in the unselected intention-to-treat population could be demonstrated, our data reinforce the use of combinations of neoadjuvant chemotherapy and ICI in this indication.

Abstract Background Immune checkpoint inhibitor treatment in non-small cell lung cancer (NSCLC) expands to early stages of disease. The neoadjuvant setting allows to investigate the mechanism-of-action of immune therapy using molecular imaging and tissue analysis. We investigated the safety and feasibility of programmed cell death ligand-1 (PD-L1) PET-imaging with 89Zr-labeled avelumab and neoadjuvant avelumab treatment in resectable NSCLC. Secondly, [89Zr]Zr-DFO-avelumab accumulation was correlated with features of the tumor immune microenvironment and pathological response. Methods This phase I-II study (NCT03514719) enrolled 20 patients with stage Ia-IIIa NSCLC who received 2 cycles of avelumab (10mg/kg Q2W) prior to surgery. In the imaging optimization part, [89Zr]Zr-DFO-avelumab PET was performed with protein doses of 2mg, 10mg or 50mg avelumab and imaging at day 2 and 4 post-injection. Subsequent patients were scanned with 10mg [89Zr]Zr-DFO-avelumab at day 4. Tracer-accumulation was correlated to PD-L1 expression and immune cell densities on pretreatment biopsies. Results [89Zr]Zr-DFO-avelumab PET/CT was successfully performed in 23/24 patients. 19/20 patients started neoadjuvant avelumab treatment, with no delays or conversions of surgical procedures. Six patients showed pathologic response, including two major pathologic responses. [89Zr]Zr-DFO-avelumab tumor-accumulation was not correlated to PD-L1 expression, but did correlate with regulatory T-cell density (r=0.72, p=0.030) and pathologic response (r=0.56, p=0.036); and was inversely correlated with CD303+ plasmacytoid dendritic cell density (r=-0.72, p=0.030). SUVpeak on baseline [18F]FDG-PET correlated with pretreatment PD-L1 expression but not with [89Zr]Zr-DFO-avelumab accumulation nor with pathologic response. Conclusion [89Zr]Zr-DFO-avelumab PET imaging is a safe and feasible approach in early-stage NSCLC. Higher [89Zr]Zr-DFO-avelumab tumor-accumulation at baseline strongly correlates with features of a suppressive tumor immune environment and response to neoadjuvant avelumab.

Abstract BACKGROUND Sonodynamic therapy, which combines a tumor cell-selective sonosensitizer with ultrasound, is gaining attention as a promising new treatment approach for glioblastoma. The objective of this case study is to report on the first applications of 5-aminolevulinic acid (5-ALA) in combination with low-intensity, non-targeted ultrasound as neo-adjuvant treatment in therapy naïve glioblastoma. MATERIAL AND METHODS Three patients with therapy naïve newly diagnosed glioblastoma were treated once before cytoreductive surgery with 5-ALA in combination with hemispheric, low-intensity, non-targeted ultrasound, assuming cell death to be triggered by non-ablative activation of 5-ALA-induced, tumor selective porphyrins. RESULTS No adverse effects were noted. Post-procedural MRI indicated a decrease in apparent diffusion coefficient values in tumors, suggesting cytotoxic effects. Relative cerebral blood volumes and leakage were increased for two patients with available perfusion imaging. Tissue obtained during surgery suggested increased cleaved-caspase III expression, a marker of apoptosis. CONCLUSION We saw an immediate marked imaging response indicating cytotoxic edema and indications of a histopathology response from just a single treatment. Correlation to clinical outcomes and extension of overall survival remains to be seen. A phase 1 safety study (NCT06665724) is now recruiting.

The Formulary Management Expert Committee (FMEC) recommends that pertuzumab in combination with trastuzumab and chemotherapy be reimbursed for the treatment of adults with early-stage HER2-positive breast cancer in the neoadjuvant setting, provided certain conditions are met. Pertuzumab in combination with trastuzumab and chemotherapy may be initiated in adult patients for the neoadjuvant treatment of early-stage HER2-positive breast cancer if all of the following conditions are met: it is locally advanced, inflammatory or early-stage breast cancer (&gt; 2 cm or node positive) and there is no evidence of metastasis. A price reduction for pertuzumab may be required.

Imatinib for palliative and adjuvant treatment of gastrointestinal stromal tumours (GISTs) with common KIT mutations has been revolutionary. For patients with locally advanced, limited metastatic or recurrent disease, neoadjuvant imatinib may downstage the tumour, enabling surgery with curative intent; however, the optimal duration of neoadjuvant imatinib is unknown. We conducted a retrospective review of patients with locally advanced, limited metastatic and recurrent GIST treated with neoadjuvant imatinib prior to consideration of surgical resection in the period 2012-2024 at three cancer centres in NSW, Australia. Baseline and outcome data were collected. The primary endpoint was the progression-free survival (PFS). A total of 30 patients were identified with 38 instances of primary locally advanced, recurrent or limited metastatic disease. The median per-patient duration of neoadjuvant imatinib was 7.8 months (range 2.9-14.9 months), and the median per-episode duration of neoadjuvant imatinib was 9.1 months (range 3.0-27.4 months). Maximum radiological response was achieved at 3.8 months for primary tumours and 6.7 months for recurrent tumours. Partial response occurred in 77% and progression in 0%. Of the 25 patients with available data, 96% were symptomatic, and 89% reported early symptomatic benefit from imatinib within 1 month. Complete surgical resection occurred in 58% of all episodes of neoadjuvant treatment. The estimated PFS rates at 2 and 5 years were 84% and 55% respectively. Overall survival rates were 84% at both 2 and 5 years. Neoadjuvant imatinib provided effective symptomatic and radiological responses in patients with locally advanced, limited metastatic or recurrent GIST. A duration of 3-6 months treatment for primary tumours and 6-12 months for recurrent disease appears sufficient for most patients. Mutational profile analysis is of particular value for patients who do not have early symptomatic benefit, have poor radiological response or have recurrent disease.

To evaluate the real clinical practice surgical outcomes following neoadjuvant nivolumab in combination with chemotherapy in a multicentre European cohort of patients. Retrospective analysis on consecutive patients treated in 6 tertiary referral hospitals in Europe with neoadjuvant chemotherapy and immunotherapy (nivolumab) for stage II-IIIB non-small cell lung cancer (March 2023-December 2024). Surgical and pathological outcomes were assessed. A total of 340 patients started neoadjuvant treatment. Three hundred seventeen patients (93.2%) were able to proceed to surgery. Forty-seven percent of patients had surgery more than 6 weeks after completion of the last neoadjuvant cycle. Two hundred eight operations (66%) were started using a minimally invasive approach with a conversion rate of 18%. The most frequent resection was lobectomy in 86% of patients. Ninety-day postoperative mortality rate was 2.5%. The pathologic complete response occurred in 95 patients (30% of the surgical patients), major pathologic response in 167 patients (52.7% of the surgical patients). The incidence of pathologic complete response (P = .78) and major pathologic response (P = .26) were similar in patients with clinical stage II and III. Pathologic complete response rate was higher in patients with programmed death-ligand 1 (PD-L1) ≥ 50% compared to those with PD-L1 < 50% (37.5% vs 27.2%, P = .082). A higher pathologic complete response (39% vs 23%, P = .004) and major pathologic response (66% vs 45%, P = .001) were observed in squamous vs non-squamous histology tumours. The use of neoadjuvant nivolumab in association with platinum-based chemotherapy in the real clinical practice is safe and effective. Our real clinical practice data represent valuable information to be used during multidisciplinary treatment selection for clinical stage II and III resectable non-small cell lung cancer and shared decision-making.

BackgroundIt is known that 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) makes a significant contribution to other diagnostic methods in determining the response to treatment after neoadjuvant chemoradiotherapy (NCRT). The study aimed to determine whether the tumor maximum standardized uptake values (SUVmax) on 18F-FDG PET/CT is predictive of overall survival (OS) in patients with rectal cancer after neoadjuvant treatment and to investigate whether the rate of change in SUVmax has a prognostic value.Materials and methodsThis retrospective study included 64 rectal cancer patients who underwent 18F-FDG PET/CT imaging, first for staging and then to assess response to neoadjuvant radiotherapy (NRT). SUVmax1 before and SUVmax2 after treatment were measured from the volume of interest (VOI). To determine the predictive value of 18F-FDG PET/CT SUVmax parameters for death, the area under the curve (AUC) and cut-off values were calculated using Receiver Operator Characteristic (ROC) analysis. Kaplan-Meier analysis was used to evaluate the effect of SUVmax cut of value on OS.ResultsTwenty-five (39%) patients were female and 39 (61%) were male. The median follow-up period was 37.5 months. The mean SUVmax1 and SUVmax2 values were 20.1 ± 9.5 and 7.6 ± 4.8, respectively. OS significantly differed when 8.5 was used as a cut-off for SUVmax2 (p = 006). 18F-FDG PET/CT metabolic tumor parameters had no significant predictive value for progression-free survival (PFS).ConclusionAccording to the results of our study, SUVmax2 after neoadjuvant treatment had a significant predictive value for OS in patients with recurrent cancer.

Rethinking tumor viability as prognostic factor in soft tissue sarcoma.

Objective: To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer. Methods: A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ2 test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results: After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences (χ²=14.374,P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ²=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ²=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ²=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ²=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ²=0.130,P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ²=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ²=0.257, P=0.522) between the two groups. Conclusion: Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.

Targeted Therapy for Recurrent and Refractory Papillary Craniopharyngioma: A Systematic Narrative Review.

Neoadjuvant chemo-immunotherapy in Non-Small Cell Lung Cancer: Can Positron Emission Tomography scan predict complete pathological response?

S316 Efficacy and Safety of Sintilimab (PD-1 Inhibitor) Combined With Anti-VEGF Therapy as Neoadjuvant Treatment in Colorectal Cancer: A Systematic Review and Proportional Meta-Analysis

Adjuvant, neoadjuvant and surgical treatment for locally advanced cervical cancer: A Bayesian network meta-analysis

Mismatch repair deficiency/microsatellite instability (dMMR/MSI-H) in rectal cancer patients treated with standard neoadjuvant therapy: a systematic review and meta-analysis.

Comprehensive dissection of rectal cancer organoids in responses to chemoradiation.