Neoadjuvant Research Articles

Tissue and imaging biomarkers of response to neoadjuvant nivolumab or nivolumab plus ipilimumab in patients with resectable hepatocellular carcinoma.

Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC. Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis of more than 70%. Data comparing patients with MPR versus those without was summarized using descriptive statistics and compared using the Wilcoxon rank sum test. Patients with MPR after neoadjuvant immunotherapy tended to have larger tumors (mean 9.52 vs. 4.99 centimeters; p = 0.050). They had a significant reduction in tumor size post-treatment (14.67% reduction vs. 9.15% increase in size; p = 0.042) and a non-significant decrease in serum AFP (-24.20% vs -14.00%; p = 0.085). Further, patients with MPR had a greater increase in intratumoral expression levels of CD8 (26.92% vs -0.04%; p = 0.026), Granzyme B (15.56% vs -2.24%; p = 0.011), and PD-1 (20.17% vs 0.40%; p = 0.048) but not PD-L1 (7.69% vs 0.57%; p = 0.26). Tumor and liver fibrosis were comparable before and after neoadjuvant therapy in patients with MPR versus non-responders. Changes in tumor size and immune cell infiltration and activation are candidate predictive markers of pathologic response to neoadjuvant immunotherapy in patients with resectable HCC.

Longitudinal monitoring of circulating tumor DNA to detect relapse early and predict outcome in early breast cancer.

Detection of molecular residual disease (MRD) allows for the identification of breast cancer patients at high-risk of recurrence, with the potential that early initiation of treatment at early stages of relapse could improve patient outcomes. The Invitae Personalized Cancer Monitoring™ assay (PCM) is a newly developed next-generation sequencing approach that utilizes up to 50 patient-specific, tumor-informed DNA variants, to detect circulating tumor DNA (ctDNA). The ability of the PCM assay to detect MRD before clinical relapse was evaluated. The cohort included 61 female patients with high-risk breast cancer who underwent neoadjuvant chemotherapy. Plasma samples were collected before and during neoadjuvant therapy, after surgery and during monitoring. PCM was used to detect ctDNA at each time point. The sensitivity to detect ctDNA in plasma from patients who relapsed during the monitoring phase was 76.9% (10/13). Specificity and positive predictive values were both 100% with all (10/61, 16%) of the patients who had ctDNA detected during the monitoring phase subsequently relapsing. Detection of ctDNA during monitoring was associated with a high-risk of future relapse (HR 37.2, 95% CI 10.5-131.9, p < 0.0001), with a median lead-time from ctDNA detection to clinical relapse of 11.7months. PCM detected ctDNA in patients who relapsed with a long lead-time over clinical relapse, shows strong association with relapse-free survival and may be used to identify patients at high-risk for relapse, allowing for earlier intervention.

Nodal involvement in patients with small, clinically node-negative HER2-positive breast cancer after staging with FDG-PET/CT and neoadjuvant systemic therapy

BackgroundGuidelines recommend systemic therapy for stage I HER2+ breast cancer (BC). Neoadjuvant systemic treatment (NAST) allows response-guided adjuvant treatment. However, prior to NAST only clinical nodal staging is available, risking undertreatment if ypN+ is observed. Here, we aim to evaluate the impact of FDG-PET/CT and NAST on nodal disease status in patients with small, node-negative HER2+ BC. MethodsThis retrospective study included patients with small (≤3 cm), clinically node-negative HER2+ BC diagnosed between 2011 and 2023. Primary outcome was the proportion of patients with nodal disease on final pathology after upfront surgery or NAST followed by surgery with or without FDG-PET/CT. Patients received either paclitaxel + trastuzumab (PT) or a more extensive regimen. ResultsOf the 370 included patients, 183 underwent FDG-PET/CT, detecting regional or distant metastases in 14 patients (7.7 %).Among 356 patients with cN0 disease, 44.1 % (n = 157/356) had upfront surgery, with only 3 % (5/157) having an FDG-PET/CT. The remaining 55.9 % (199/356) started with NAST, with 82 % (n = 164/199) having an FDG-PET/CT. Among patients treated with NAST, 36 % received PT.Nodal involvement on pathology was seen in 19.1 % (n = 29/152) after upfront surgery without FDG-PET/CT and 6.1 % (10/164) after NAST combined with FDG-PET/CT.After NAST, 58 % had a pCR (PT: 49 %, other: 63 %). Nodal involvement on final pathology was seen in 6.9 % after PT and in 5.5 % after more extensive regimen. ConclusionsThe proportion of patients with ypN + after NAST combined with FDG-PET/CT was only 6.1 %. Neoadjuvant treatment can be a safe treatment strategy for patients with stage I HER2+ BC.

Prognostic Significance of Chemotherapy Response Score in Patients Undergoing Interval Debulking Surgery and Attained Complete Cytoreduction for High-Grade Serous Tubal and Ovarian Carcinoma

Objectives The chemotherapy response score (CRS) has been described to assess the pathological response to chemotherapy in patients with high-grade serous tubal and ovarian carcinoma. The main aim of this study was to assess the prognostic significance of CRS in patients who underwent interval debulking surgery and attained complete cytoreduction. Materials and Methods A retrospective study was conducted on patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIIC and IV high-grade serous tubal and ovarian carcinomas who had undergone surgery after three to four cycles of neoadjuvant chemotherapy and attained complete cytoreduction from January 2015 to July 2018. Results A total of 125 patients were included in the study. The median age of the patients was 52 years. There were 21 patients (16.8%) with a CRS of 1, 53 patients (42.4%) with a CRS of 2, and 51 (40.8%) patients with a CRS of 3. The median follow-up period was 77 months. The CRS applied on the omental samples showed significant correlation with progression-free survival (PFS; CRS of 1 vs. 2: median PFS, 17 vs. 22 months; hazard ratio, 1.73; and CRS of 2 vs. 3: median PFS, 22 vs. 54 months; hazard ratio, 2.32) and overall survival (OS; CRS of 1 vs. 2: median OS, 19 vs. 40 months; hazard ratio, 2.13; CRS of 2 vs. 3: median OS, 40 months vs. not reached; hazard ratio, 2.19). Conclusion Our study confirms that the omental CRS is significantly associated with PFS and OS in patients who attained complete cytoreduction during interval debulking surgery.

Survival Outcomes of Neoadjuvant Therapy Followed by Sleeve Lobectomy in Non-Small Cell Lung Cancer

This study was carried out to evaluate the impact of neoadjuvant therapy on long-term survival in non-small cell lung cancer (NSCLC) patients undergoing sleeve lobectomy. A total of 613 patients were retrospectively analyzed, including 124 who received neoadjuvant therapy. A 1:2 Propensity score matching (PSM) method was adopted to create a balanced cohort including 110 with neoadjuvant therapy and 169 without neoadjuvant therapy. Survival was estimated using the Kaplan-Meier method and compared using the Log-rank test and Cox proportional hazards models. Neoadjuvant therapy was associated with improved 3-year DFS (73.6% vs. 54.4%, P<0.001) and OS (80.9% vs. 63.9%, P=0.002) compared to patients without neoadjuvant therapy. Moreover, neoadjuvant chemoimmunotherapy significantly improved 3-year DFS (85.3% vs. 54.4%, P=0.001) and OS (88.2% vs. 63.9%, P=0.006), whereas chemotherapy alone did not show a significant effect. Multivariable Cox regression analysis revealed that neoadjuvant therapy was an independent predictor of improved DFS and OS while pathological N2 stage was independently associated with poorer DFS and OS. Furthermore, subgroup analysis in the neoadjuvant arm revealed that pathological N2 stage was an independent risk factor for DFS (HR, 3.830; 95% CI, 1.687-8.694; P=0.001), and achieving major pathologic response (MPR) was an independent predictor for better OS (HR, 0.120; 95% CI, 0.015-0.933; P=0.043). Neoadjuvant therapy prior to sleeve lobectomy significantly increased DFS and OS in locally advanced NSCLC. Sleeve lobectomy is advisable followed by neoadjuvant therapy, especially with chemoimmunotherapy.

The use of a clip prior to neoadjuvant chemotherapy for breast cancer with microcalcifications may not always be required.

Neoadjuvant chemotherapy is now a common first line therapy for breast cancer. International guidelines recommend placement of a clip before commencement of therapy to assist with localizing the tumor bed in the event of excellent response-this takes up time and resources. The microcalcifications associated usually persist after chemotherapy and could serve as an alternative marker. We investigated to determine prognostic criteria to avoid the need for a marker clip before neoadjuvant chemotherapy for breast tumors associated with microcalcifications. We performed a 7year single-center bi-site retrospective analytical observational study of 88 women with calcified breast carcinoma treated by neoadjuvant chemotherapy at our bi-site institution between September 2015 and September 2022. This study includied two groups (clip-free tumor localization vs. clip-free tumor non-localization), and investigating quantitative and qualitative predictive factors. The clip-free tumor localization after neoadjuvant chemotherapy was defined by the visibility of residual calcifications on both views of the pre-operative mammogram on the day of or the day prior to surgery. The mean age of the 88 women included in our population was 52.8years (± 12.7years standard deviation). Of the 90 tumors with microcalcifications, 64 carcinomas (71.1%) were localizable with no marker clip after neoadjuvant chemotherapy. The main predictive factors significantly associated with clip-free tumor localization were number of calcifications > 10 (P < 0.0001), grade 2 tumor (P = 0.003) with a probability of locating tumor after neoadjuvant chemotherapy of 97.9%, 95% CI [95.6; 99.0]. More than 10 microcalcifications in a grade 2 breast tumor at the initial diagnosis may obviate the need for a marker clip.

Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

The authors hypothesized that small ribonucleic acid (sRNA) obtained from blood samples after neoadjuvant therapy from patients treated with neoadjuvant chemoradiation therapy (NACRT) could serve as a novel biomarker for predicting pathologic complete response (pCR). This study included 99 patients treated with esophagectomy after NACRT between March 2010 and October 2021 whose blood samples were collected between the end of NACRT and surgery. Next-generation sequencing (NGS) was used to analyze sRNAs from the blood samples. A predictive model for pCR comprising micro-RNA isoforms (isomiR), transfer RNA (tRNA)-derived sRNAs (tsRNAs), and clinical factors was constructed using cross-validation. Of the 99 patients, pCR was diagnosed for 30 and non-pCR for 69 of the patients. Among sRNAs, the isomiRs of let-7b and miR-93 and the tsRNA group derived from tRNA-Gly-CCC/GCC were identified as predictive factors. The clinical factors included a decrease in the maximum standardized uptake value (SUVmax) at the primary site, clinical complete response post-NACRT, preoperative biopsy, and post-NACRT carcinoembryonic antigen levels. The combined predictive model for pCR (C-PM) was established using the three sRNAs and four clinical factors. The area under the curve for the C-PM was 0.84, which was a significant factor in the multivariate analysis (odds ratio, 89.41; 95 % confidence interval 8.1-987.5; p < 0.001). Pathologic complete response after NACRT can be predicted by a predictive model constructed from preoperative clinical factors obtained via minimally invasive procedures and sRNA identified by NGS. Preoperative pCR prediction may influence treatment decision-making after NACRT.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Impact of Clipped Node as a Sentinel Lymph Node on Axillary Staging Following Neoadjuvant Chemotherapy in Clinically Node-Positive Breast Cancer.

Residual disease after neoadjuvant chemotherapy (NAC) is prognostic and informs adjuvant treatment. Targeted axillary dissection (TAD) following NAC has low false-negative rates, facilitating accurate axillary staging. This study evaluates the clipped node status in axillary staging utilizing TAD. Retrospective review identified cN1 breast cancer patients treated with NAC and TAD from July 2013 to June 2023. Nodal ultrasound and biopsy defined cN1 status. Patient, tumor, and treatment characteristics were compared based on clipped node status (sentinel lymph node [SLN] or non-SLN). Multivariate analysis of factors associated with theclipped node as anon-SLN was performed. A total of 680 patients underwent TAD, 94.6% with dual-tracer mapping. In three patients (0.4%), no SLN was identified. The clipped node was a SLN in 610 patients (90%) and non-SLN in 70 (10.3%). When the clipped node was a non-SLN, 42 (60%) were positive for metastasis. In 22 of 42 patients (52%), the clipped non-SLN was the only positive node. The clipped non-SLN cohort had a higher proportion with >3 suspicious nodes at presentation (p = 0.003), fewer SLNs excised (mean 2.2 vs. 3.5, p ≤ 0.001), and fewer positive SLNs (p ≤ 0.001). On multivariate analysis, >3 suspicious nodes on ultrasound (odds ratio 3.0, p = 0.001) and tumor size at presentation (odds ratio 0.9, p = 0.02) were significantly associated with theclipped node as anon-SLN. When the clipped node was a non-SLN, half of the time it was the only positive node and only residual disease on TAD. Given implications for adjuvant therapy, selective clipped node excision is recommended for precise identification of residual disease after NAC.

Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy—a systematic review and meta-analysis

Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy—a systematic review and meta-analysis

Androgen deprivation therapy, neoadjuvant androgen deprivation therapy, and adjuvant androgen deprivation therapy in patients with locally advanced prostate cancer: a multi-center real-world retrospective study.

Determining the potential benefit of neoadjuvant androgen deprivation therapy (ADT) and adjuvant ADT in patients with locally advanced prostate cancer (LAPC) undergoing complete resection. 139 patients diagnosed with cT3-4, or cN+ LAPC in Xiangya Hospital and The First Affiliated Hospital of University of South China from 2010 to 2021 were collected. Cancer-specific survival (CSS) and overall survival (OS) of patients were assessed using Kaplan-Meier and Cox proportional risk analysis. We also analyzed the functional outcomes of two subgroups of patients who underwent radical prostatectomy (RP). Of the 182 patients with cT3-4, or cN+ LAPC, 139 patients (76.4%) were enrolled in the study with a 5-year survival rate of 82.3%. 45 patients (32.4%) received ADT alone, 46 patients (33.1%) received neoadjuvant ADT before surgery, and the remaining 48 patients (34.5%) received surgery with adjuvant ADT. Neoadjuvant ADT before surgery and surgery with adjuvant ADT were associated with significantly improved survival compared with ADT alone. Multivariate Cox models showed that neoadjuvant ADT before surgery (hazard ratio [HR], 0.29; 95% CI 0.13-0.92) or surgery with adjuvant ADT (HR, 0.26; 95% CI 0.16-0.78) was associated with improved CSS compared with ADT alone. Regional lymph node metastasis, positive lymphovascular invasion, and Gleason score 9 + were independent predictors of LAPC CSS and OS. More patients in the neoadjuvant ADT before surgery group achieved final continence status within 12 months after surgery (93.48% v 77.08%). CSS and OS were significantly prolonged in cT3-4, or cN+ LAPC patients who received neoadjuvant ADT before surgery and surgery with adjuvant ADT compared to ADT alone.

Prognosis related to treatment plan in patients with biliary tract cancer: A nationwide database study

BackgroundBiliary tract cancer (BTC) is a malignancy characterized by a low 5-year survival rate (<20 %). Clinical aspects such as tumor resectability, Eastern Cooperative Oncology Group performance status score (ECOG-PS), and molecular profiling are used to determine the treatment for these patients. Diagnosis and treatment are typically established by a multidisciplinary team (MDT). However, standardized practices for BTC are lacking, and there is a need to assess the impact of current MDT treatment decisions on BTC outcomes. The purpose of this study was to investigate the role of the treatment plan proposed by the first MDT conference on survival in patients with BTC, and to identify risk factors for poor survival in this population. MethodThis nationwide, multicenter, retrospective cohort study examined data from the Danish Liver Cancer Group (2013–2020) with confirmed BTC diagnoses. Multiple imputation was used to handle missing data. Survival and variable-survival rate relationships were analyzed using the Kaplan-Meier estimator, and the Cox regression model, respectively. ResultsEligible BTC-confirmed cases: n=1923. The overall median survival was 7.7 months (95 % CI: 7.1–8.5), with a 5-year survival rate of 16.3 %. Patients over 70 years of age, with ECOG-PS 3 or 4, non-operable cases, and with unresectable tumors had lower survival rates. Surgery as the first therapeutic option showed the highest median survival (33.1 months, 95 % CI: 27.2–41.6; p < 0.0001). Multivariable analysis showed that poor ECOG-PS, palliative and neoadjuvant chemotherapy, stereotactic radiotherapy, and best supportive care significantly increased mortality risk in patients with BTC (p=0.05). ConclusionAmong the therapeutic options prescribed by the MDT for patients with BTC, surgery offered the best survival rates, likely due to patient-related prognostic factors. High ECOG-PS was linked to an increased mortality risk regardless of age, highlighting the importance of this criterion in treatment decisions.

The Predictive Role of Radiomics in Breast Cancer Patients Imaged by [18F]FDG PET: Preliminary Results from a Prospective Cohort.

Recently, radiomics has emerged as a possible image-derived biomarker, predominantly stemming from retrospective analyses. We aimed to prospectively assess the predictive role of [18F]FDG-PET radiomics in breast cancer (BC). Patients affected by stage I-III BC eligible for neoadjuvant chemotherapy (NAC) staged with [18F]FDG-PET/CT were prospectively enrolled. The pathological response to NAC was assessed on surgical specimens. From each primary breast lesion, we extracted radiomic PET features and their predictive role with respect to pCR was assessed. Uni- and multivariate statistics were used for inference; principal component analysis (PCA) was used for dimensionality reduction. We analysed 93 patients (53 HER2+ and 40 triple-negative (TNBC)). pCR was achieved in 44/93 cases (24/53 HER2+ and 20/40 TNBC). Age, molecular subtype, Ki67 percent, and stage could not predict pCR in multivariate analysis. In univariate analysis, 10 radiomic indices resulted in p < 0.1. We found that 3/22 radiomic principal components were discriminative for pCR. Using a cross-validation approach, radiomic principal components failed to discriminate pCR groups but predicted the stage (mean accuracy = 0.79 ± 0.08). This study shows the potential of PET radiomics for staging purposes in BC; the possible role of radiomics in predicting the pCR response to NAC in BC needs to be further investigated.

Outcome of Ewing sarcoma in children: Twenty years experience from a single center

ABSTRACT Objective: Ewing sarcoma (ES) is a significant malignancy in pediatric patients, with a notable impact on bone health. Despite advances in treatment, ES still poses challenges, particularly in cases of metastasis or relapse. This study aims to evaluate the outcomes of ES in children treated at our center over a twenty-year period. Patients and Methods: We retrospectively reviewed pediatric patients diagnosed with ES at our center between January 2004 and February 2024. Data including demographic information, tumor characteristics, treatment modalities, and survival outcomes were analyzed. Results: Among 986 pediatric solid tumor cases, 137 (13.8%) were diagnosed with ES. After excluding ineligible cases, 115 ES cases were included in the study. The most common sites of involvement were the lower extremities. Metastatic disease was observed in 35.8% of cases, with the lungs being the most common site. Advanced age, and pelvic involvement were associated with poor prognosis. Histopathological response to neoadjuvant chemotherapy, represented by tumor necrosis rate, metastatic and relapse disease significantly influenced survival outcomes. Conclusion: Despite multimodal therapies, ES in children, especially with metastatic disease or relapse, presents a challenging prognosis. Early diagnosis and the development of novel treatment strategies are imperative to improve outcomes for these patients.

Does maximal effort cytoreductive surgery after 6-cycles of chemotherapy play a role in the management of advanced ovarian cancer?

The current gold standard in the surgical management of advanced ovarian cancer recommended by ESGO and ASCO is complete resection of all visible disease. If this is not deemed possible in the upfront setting, then interval cytoreductive surgery should be undertaken after 3-4-cycles of neo-adjuvant chemotherapy. Occasionally, surgery in the interval setting may not be possible either due to factors associated with patient fitness, or due to persistence of disease in sites deemed unresectable on interval scanning. Limited published data assessing outcomes from surgery delayed to after 6-cycles of NACT (delayed cytoreductive surgery) suggests a potential benefit over no surgery and suggests that if interval cytoreductive surgery is not possible, then the clinician might consider delayed surgery on a case by case basis. We sought to review the outcomes of patients with Advanced Ovarian Cancer presenting to the Northern Gynaecological Oncology Centre who underwent delayed surgery. This study is a retrospective analysis looking at patients with epithelial ovarian cancer of FIGO stage IIIC and above, who were not deemed suitable to undergo either primary or interval cytoreductive surgery, referred to the Northern Gynaecological Oncology Centre Gateshead, UK, between January 2014 and December 2020. We compared survival outcomes in women receiving non-standard treatment for advanced ovarian cancer, comparing two groups of patients; those completing at least six cycles of platinum-based chemotherapy as part of their first-line treatment and not having surgery with those who received delayed cytoreductive surgery after completing of 6-cycles of primary chemotherapy. A total of 89 cases were included in the analysis and 78/89 patients had completed at least 6-cycles of primary chemotherapy in the first-line treatment setting without any attempt at surgical cytoreduction. 11/89 patients underwent DDS after completion of 6-cycles of primary chemotherapy. The majority of included cases 87/89 (98%) were high-grade serous ovarian cancer (HGSOC). Surgery and no-surgery groups were well matched in terms of stage comparison at presentation with an overall stage distribution of 62% FIGO stage IIIC, 10% stage IVA and 28% stage IVB. The surgery group were significantly younger than the no-surgery group with median age of 68 (interquartile range (IQR) 59-71years) and 77years (IQR 70-82years) (p < 0.01), respectively. The overall survival (OS) of the surgery and no-surgery groups was 25months and 23months, respectively (p = 0.38) with a median follow-up of 20months (IQR 11-29months). The 1year disease-specific mortality for both groups was 18%. Maximal effort cytoreductive surgery after 6-cycles is not associated with a survival benefit (even with complete cytoreduction) but may be considered in the context of symptomatic disease or for palliation of symptoms amenable to surgery.

Minimizing overtreatment and maximizing oncologic outcomes in upper tract urothelial carcinoma

Purpose of review An update on the latest advances in the management of upper tract urothelial carcinoma (UTUC), with an emphasis on strategies to optimize oncologic outcomes while minimizing overtreatment. Recent findings Recent high-quality trials have changed the landscape of UTUC treatment. Emerging tools including 3D histology and measurement of cell free tumor DNA may improve diagnostic accuracy of disease grading and staging, and be used in monitoring treatment response. Novel therapies show promise of reducing low-grade UTUC disease recurrence at the cost of significant side-effects. Platinum-based neoadjuvant chemotherapy in high-grade/muscle-invasive disease showed complete pathological response in a subset of patients, but difficult to predict responders. Adjuvant platinum-based chemotherapy exhibited a clear survival benefit, but immunotherapy did not, suggesting possible overtreatment with these agents. Molecularly-targeted therapies in metastatic UTUC have shown the greatest recent oncologic advances, but exhibit a high adverse event-rate. Summary Low-grade UTUC has the potential for overtreatment, as it exhibits low metastatic-potential and excellent survival. For high-grade and advanced-stage UTUC, these carry high mortality rates and require more aggressive treatment, but studies are limited by inaccurate grading and staging which can lead to overtreatment especially in the neoadjuvant setting. Emerging technologies will help improve diagnostic accuracy and noninvasive monitoring of treatment response.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Insights from the Western Australian Context.

Recent studies have associated total neoadjuvant therapy (TNT) with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, real-world experience with TNT in the management of LARC remains limited. This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia. Patients with LARC (cT2-4 and/or cN1-2) who underwent induction chemotherapy followed by neoadjuvant chemoradiotherapy or neoadjuvant chemoradiotherapy followed by consolidation chemotherapy, followed by surgery were recruited from two hospitals in Western Australia. Efficacy outcomes assessed included clinical response (complete, partial, no response), and pathologic complete response (pCR) rate, R0 resection rate, and R1 resection rate were evaluated. Those patients who achieved clinical complete response following TNT were given the option of active surveillance. The safety and tolerability of TNT were assessed. 32 patients with LARC were treated with TNT. In total, 17 patients (53%) received chemoradiotherapy followed by consolidation chemotherapy and 15 patients (47%) received induction chemotherapy followed by chemoradiotherapy. Nine (28%) of the patients with LARC treated with TNT had a complete clinical response, twenty-one (66%) patients had a partial clinical response, and two (6%) patients had no response to TNT. Of the 32 patients, 27 (84%) underwent surgery. There was a 100% R0 resection rate. The pCR rate was 15%. pCR, clinical response, and the R0 resection rate were similar between the two TNT regimens. TNT was well tolerated, with the majority of patients (88%) completing the chemotherapy course with grade 1 and 2 adverse effects. In conclusion, TNT emerges as a promising approach for the management of LARC. However, further research is warranted to refine the optimal TNT protocols, determine its long-term outcomes, and identify patient populations who would benefit the most from this innovative therapeutic strategy.

The association of the chemotherapy response score and homologous recombination deficiency in patients undergoing interval tumor reductive surgery following neoadjuvant chemotherapy

ObjectivesIn patients undergoing interval tumor reductive surgery, a good response to neoadjuvant chemotherapy may limit available tumor for homologous recombination deficiency testing. The objective of this study was to assess...

Upfront surgery, neoadjuvant chemoradiotherapy, or neoadjuvant chemotherapy for rectal cancer with lateral lymph node metastasis: A multicenter MRI and lateral lymph node dissection study

AbstractAimThe purpose was to clarify the oncological outcomes of rectal cancer (RC) with lateral lymph node metastasis (LLNM) on high‐resolution MRI (HRMRI), considering preoperative treatments.MethodsTwo hundred and twelve patients, from 13 hospitals, diagnosed with RC with lateral lymph node dissection (LLND), between 2017 and 2019, were prospectively registered. LLNM was defined as a short‐axis size ≥5 mm. Ultimately, this study included 102 patients. Upfront surgery (Upfront), chemoradiotherapy (CRT), and neoadjuvant chemotherapy (NAC) were performed at each institution's discretion.ResultsSixty‐six (64.7%) had mesorectal fascia (MRF) involvement, 35 (34.3%) had extramural venous invasion, and 33 (32.4%) had bilateral LLNMs. A positive radial margin (RM1) was observed in nine patients (8.8%), and 35 (34.3%) had pathological LLNM (pLLNM). Overall, 3‐year relapse‐free survival (3yRFS) and local recurrence‐free survival (3yLRFS) were 69.6% and 92.9%. Upfront 3yRFS (N = 54), CRT (N = 23) and NAC (N = 25) constituted 62.9%, 82.6%, and 72.0%; 3yLRFS was 92.4%, 100%, and 88.0%. RM1 and pLLNM were significantly associated with LRFS (RM0 vs. RM1, 3yLRFS 96.7% vs. 50.0%; pLLNM negative vs. positive, 97.0% vs. 84.7%). 3yRFS Upfront non‐MRF (N = 21), post CRT non‐MRF (N = 15), and post NAC non‐MRF (N = 14) were 61.9%, 86.7%, and 100%; 3yLRFS was 90.2%, 100%, and 100%.ConclusionsGood local control of Upfront LLND for RC with LLNM was shown, but multidisciplinary treatments were required. CRT followed by surgery was preferable for RC with LLNM, but a radiation‐sparing strategy is promising for post NAC non‐MRF.

Successful Outcome of Stage IB3 Cervical Cancer Treated With Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy: A Case Report

Successful Outcome of Stage IB3 Cervical Cancer Treated With Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy: A Case Report