Completion Of Adjuvant Therapy Research Articles

The impact of preoperative renal insufficiency on the outcomes of patients with pancreatic cancer undergoing pancreaticoduodenectomy.

This study evaluated the impact of renal function impairment on long-term survival outcomes and adjuvant therapy in patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD). In this study, 264 patients who underwent PD for pancreatic head cancer between 2011 and 2021 were retrospectively analyzed. The patients were subsequently categorized into three groups according to the estimated glomerular filtration rate: normal group (> 90 mL/min/1.73 m2, n = 73), moderate group (45-90 mL/min/1.73 m2, n = 176), and severe group (< 45 mL/min/1.73 m2, n = 15). The primary outcomes evaluated were postoperative complications, overall survival (OS), and relapse-free survival (RFS). Additionally, the completion of adjuvant therapy and risk factors for adjuvant therapy discontinuation were analyzed. The total proportion of patients with complications was significantly higher in the severe group (p = 0.008). The proportion of patients with severe complications (Clavien-Dindo classification ≥ IIIa) did not significantly differ between the chronic kidney disease (CKD) groups (p = 0.730). The proportion of patients in whom adjuvant therapy was completed was notably lower in the severe group (p = 0.011). Multiple logistic regression analysis revealed that CKD groups and hemoglobin levels ≤ 11.5g/dL were independent predictors of adjuvant therapy completion failure (p = 0.016 and p = 0.016). There was no significant difference in the OS and RFS rates between the CKD groups (p = 0.499, p = 0.688). In patients with pancreatic cancer and CKD, performing PD safely may be feasible; however, adjuvant therapy completion is challenging.

Ultrashort Cell-Free DNA Fragments and Vimentin-Positive Circulating Tumor Cells for Predicting Early Recurrence in Patients with Biliary Tract Cancer.

Background/Objectives: Biliary tract cancer (BTC) is a rare but aggressive malignancy that requires surgical treatment. However, postoperative recurrence rates are high, and reliable predictors of recurrence are limited. This study aimed to investigate the effectiveness of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) in predicting early recurrence after curative surgery and complete adjuvant therapy in patients with BTC. Methods: Twenty-four patients who underwent R0 and R1 resections and completed adjuvant therapy for BTC between September 2019 and March 2022 were followed up until March 2024. Patients were categorized into early recurrence (ER) and non-ER groups, using one year as the cutoff for recurrence. Results: The combination score derived from ultrashort fragments of cfDNA, vimentin-positive CTCs, and carbohydrate antigen (CA) 19-9 levels showed a statistically significant difference between the ER and non-ER groups (p-value < 0.001). The receiver operating characteristic curve from the combination score and CA 19-9 levels yielded areas under the curve of 0.891 and 0.750, respectively. Conclusions: Although further research is required, these findings suggest that cfDNA and CTCs may increase the accuracy of predicting postoperative recurrence in patients with BTC.

Yiqi Wenyang Jiedu prescription for preventing and treating postoperative recurrence and metastasis of gastric cancer: a randomized controlled trial protocol.

Postoperative recurrence and metastasis of gastric cancer (GC) are primary factors that contribute to poor prognosis. GC recurs at a rate of approximately 70%-80% within 2 years after local treatment and approximately 90% within 5 years. "Yang-deficient toxic node" is the core pathogenesis of GC recurrence and metastasis. The Yiqi Wenyang Jiedu prescription (YWJP), a form of complementary and alternative medicine in China, is an empirical remedy to prevent postoperative recurrence and metastasis of GC. Taking the main therapeutic principles of "nourishing Qi and warming Yang, strengthening Zhengqi, and detoxifying" can aid in preventing the recurrence and metastasis of GC in patients during the watchful waiting period after surgery and adjuvant chemotherapy. This approach aims to enhance the quality of life of patients. However, high-quality evidence to support this hypothesis is lacking. This study will aim to investigate the efficacy and safety of YWJP to prevent and treat postoperative metastasis and GC recurrence. The study will be a multicenter, randomized, double-blind, placebo-parallel-controlled clinical trial. A total of 212 patients who completed adjuvant chemotherapy within 8 months of radical gastrectomy will be enrolled. Patients in the intervention group will receive the YWJP, whereas those in the control group will receive a placebo. The main outcome was the disease-free survival (DFS) rate 2 years after surgery. The secondary outcomes included DFS time, overall survival, annual cumulative recurrence and rate of metastasis after 1-3 years, cumulative annual survival after 1-3 years, fat distribution-related indicators, tumor markers, peripheral blood inflammatory indicators, prognostic nutritional index, symptoms and quality of life evaluation, medication compliance, and adverse reaction rate. There is a lack of effective therapy after the completion of adjuvant therapy during the postoperative period of watchful waiting. This study will be the first randomized clinical trial to evaluate whether complementary and alternative medical interventions can effectively prevent recurrence and metastasis during the watchful waiting period after GC surgery and to provide evidence for surveillance treatment management after GC surgery. ClinicalTrials.gov, identifier NCT05229809.

Abstract A008: Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting

Abstract Objectives: Historically, African-American/Black patients with bladder cancer have worse clinical outcomes compared with White/Caucasian patients. In the CheckMate 274 trial, nivolumab demonstrated a significant improvement in disease-free survival compared with placebo among patients with MIUC at high risk of recurrence following radical surgery; however, African-American/Black patients were underrepresented (&amp;lt; 1%). The objective of this analysis was to describe the characteristics and outcomes of MIUC patients treated with adjuvant nivolumab across different racial subgroups in a real-world setting. Methods: This US retrospective medical chart review included African-American/Black and White/Caucasian patients with MIUC treated with adjuvant nivolumab following radical resection between 01-Sep-2021 and 10-Sep-2022. Patient characteristics and outcomes were abstracted from the medical charts by treating oncologists. Patient characteristics and landmark survival estimates based on Kaplan-Meier analyses were summarized descriptively. Results: The analysis included 223 patients (African-American/Black: 62; White/Caucasian: 161). A numerically higher proportion of African-American/Black vs White/Caucasian patients, respectively, was male (74.2% vs 66.5%), less than 60 years old (27.4% vs 20.5%), unemployed (16.1% vs 5.6%), and had Medicaid at therapy initiation (14.5% vs 6.2%). Similar proportions in both groups had ECOG performance status 0-1 (82.3% vs 82.6%), received neoadjuvant therapy (58.1% vs 56.5%), and completed adjuvant therapy (67.7% vs 66.5%). The median follow-up time (12.5 months vs 13.1 months) and median duration of adjuvant therapy (11.0 months vs 11.3 months) were comparable. Similar estimates were observed for 12-month overall survival (96.7% vs 91.4%), 12-month disease-free survival (88.3% vs 88.4%), and 12-month distant metastasis-free survival (88.3% vs 88.4%). Conclusions: Despite higher rates of socio-economic risk factors among African-American/Black patients, this real-world study suggests similar effectiveness of adjuvant nivolumab among MIUC patients across African-American/Black and White/Caucasian patient populations. Citation Format: Regina Barragan-Carrillo, Alexander Chehrazi-Raffle, Bruce Feinberg, William S. John, Taavy A. Miller, Sarah Lucht, Prathamesh Pathak, Emily Bland, Sarah Gordon, JaLyna Laney, Andrew J. Klink, Hedyeh Ebrahimi, Nisha Singh, Carmelo Alonso, Miraj Patel, Lisa Rosenblatt, Xin Yin. Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A008.

Abstract PS06-06: Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer

Abstract Background: The detection of ctDNA in patients with early-stage breast cancer after completion of adjuvant therapy is associated with a high risk of recurrence. Current clinical guidelines do not recommend routine screening for metastatic disease unless there are clinical signs and symptoms in patients who completed adjuvant therapy. However, ctDNA may serve as an early biomarker of recurrence which may allow effective identification of patients with asymptomatic distant metastases or molecular relapse only, who could benefit from early treatment intervention. Herein, we utilized a tissue-free, multiomic assay for the sensitive and specific detection of MRD in patients with early-stage breast cancer. Methods: Plasma samples were collected from patients with stage I-III breast cancer who were enrolled in the SUCCESS-A phase 3 clinical trial (NCT02181101) between 2006 and 2007. All patients received adjuvant chemotherapy +/- endocrine therapy and/or anti-HER2 therapy. Samples were collected approximately two years after completion of adjuvant chemotherapy, and plasma samples selected for analysis were from patients without evidence of disease recurrence prior to sample collection. Presence of MRD was assessed using Guardant Reveal powered by Infinity, which evaluates the epigenomic signals associated with cancer versus normal DNA for the detection of ctDNA. Samples with the presence of ctDNA are characterized for somatic alterations with common sources of interference such as clonal hematopoiesis excluded. An analytically validated bioinformatics pipeline was used for the detection of breast cancer ctDNA. Samples were analyzed blinded to the clinical data. Median survival times were estimated using the Kaplan-Meier method and hazard ratios were calculated based on univariable cox regression models. Results: A total of 311 plasma samples from 311 patients were evaluable. ctDNA was detected in 34% (13/38) of patients who subsequently developed distant recurrence and in none (0/7) of the patients who had local or contralateral breast cancer recurrence. ctDNA was detected in 60% (9/15) of samples that were collected within one year before recurrence. In the ctDNA detected samples from patients who had disease recurrence, the median time from sample collection to recurrence was 7.9 months (range, 1.4-28.6 months). ctDNA was detected in 6 patients who did not have a documented disease recurrence, resulting in a specificity of 97.7% (260/266). In the overall cohort, ctDNA detection was prognostic for recurrence-free survival (RFS; HR 11.0, 95% CI 2.28-53.6; p&amp;lt; 0.0001), distant recurrence-free survival (D-RFS; HR 13.7, 95% CI 2.52-74.9; p&amp;lt; 0.0001), and overall survival (OS; HR 17.4, 95% CI 1.33-227; p&amp;lt; 0.0001). Conclusion: Detection of ctDNA after adjuvant chemotherapy was highly prognostic and demonstrated high specificity in an early-stage breast cancer cohort. Larger, prospective studies are needed to confirm the prognostic value of ctDNA in the post-treatment setting and assess the clinical utility of MRD detection in this population. Citation Format: Wolfgang Janni, Thomas Friedl, Brigitte Rack, Peter A. Fasching, Andreas Hartkopf, Hans Tesch, Ralf Lorenz, Georg Heinrich, Jens-Uwe Blohmer, Tanja Fehm, Volkmar Müller, Andreas Schneeweiss, Matthias Beckmann, Matthias Ruebner, Nadia Harbeck, Klaus Pantel, Derek Dustin, Mingyang Cai. Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS06-06.

Exploring the impact of primary care utilization and health information exchange upon treatment patterns and clinical outcomes of glioblastoma patients.

There is limited literature describing care coordination for patients with glioblastoma (GBM). We aimed to investigate the impact of primary care and electronic health information exchange (HIE) between neurosurgeons, oncologists, and primary care providers (PCP) on GBM treatment patterns, postoperative outcomes, and survival. We identified adult GBM patients undergoing primary resection at our institution (2007-2020). HIE was defined as shared electronic medical information between PCPs, oncologists, and neurosurgeons. Multivariate logistic regression analyses were used to determine the effect of PCPs and HIE upon initiation and completion of adjuvant therapy. Kaplan-Meier and multivariate Cox regression models were used to evaluate overall survival (OS). Among 374 patients (mean age ± SD: 57.7 ± 13.5, 39.0% female), 81.0% had a PCP and 62.4% had electronic HIE. In multivariate analyses, having a PCP was associated with initiation (OR: 7.9, P < 0.001) and completion (OR: 4.4, P < 0.001) of 6 weeks of concomitant chemoradiation, as well as initiation (OR: 4.0, P < 0.001) and completion (OR: 3.0, P = 0.007) of 6 cycles of maintenance temozolomide thereafter. Having a PCP (median OS [95%CI]: 14.6[13.1-16.1] vs. 10.8[8.2-13.3] months, P = 0.005) and HIE (15.40[12.82-17.98] vs. 13.80[12.51-15.09] months, P = 0.029) were associated with improved OS relative to counterparts in Kaplan-Meier analysis and in multivariate Cox regression analysis (hazard ratio [HR] = 0.7, [95% CI] 0.5-1.0, P = 0.048). In multivariate analyses, chemoradiation (HR = 0.34, [95% CI] 0.2-0.7, P = 0.002) and maintenance temozolomide (HR = 0.5, 95%CI 0.3-0.8, P = 0.002) were associated with improved OS relative to counterparts. Effective care coordination between neurosurgeons, oncologists, and PCPs may offer a modifiable avenue to improve GBM outcomes.

Thrombus or tumor? A case report of a rare sarcoma entity: intimal sarcoma of the pulmonary arteries

BackgroundTumor embolism is a very rare primary manifestation of cancers and the diagnosis is challenging, especially if located in the pulmonary arteries, where it can mimic nonmalignant pulmonary embolism. Intimal sarcoma is one of the least commonly reported primary tumors of vessels with only a few cases reported worldwide. A typical location of this malignancy is the pulmonary artery. Herein, we present a case report of an intimal sarcoma with primary manifestation in the pulmonary arteries.Case summaryA 53-year-old male initially presented with dyspnea. On imaging, a pulmonary artery embolism was detected and was followed by thrombectomy of the right ventricular outflow tract, main pulmonary artery trunk, and right pulmonary artery after ineffective lysis therapy. Complementary imaging of the chest and abdomen including a PET-CT scan demonstrated no evidence of a primary tumor. Subsequent pathology assessment suggested an intimal sarcoma further confirmed by DNA methylation based molecular analysis. We initiated adjuvant chemotherapy with doxorubicin. Four months after the completion of adjuvant therapy a follow-up scan revealed a local recurrence without distant metastases.DiscussionPrimary pulmonary artery intimal sarcoma (PAS) is an exceedingly rare entity and pathological diagnosis remains challenging. Therefore, the detection of entity-specific molecular alterations is a supporting argument in the diagnostic spectrum. Complete surgical resection is the prognostically most important treatment for intimal cardiac sarcomas. Despite adjuvant chemotherapy, the prognosis of cardiac sarcomas remains very poor. This case of a PAS highlights the difficulty in establishing a diagnosis and the aggressive natural course of the disease.ConclusionIn case of atypical presentation of a pulmonary embolism, a tumor originating from the great vessels should be considered. Molecular pathology techniques support in establishing a reliable diagnosis.

Capivasertib: A Novel AKT Inhibitor Approved for Hormone-Receptor-Positive, HER-2-Negative Metastatic Breast Cancer.

To review the pharmacology, efficacy, and safety of capivasertib for the treatment of adults with hormone receptor-positive, HER2-negative (HR+/HER2-) locally advanced or metastatic breast cancer with 1 or more PIK3CA/AKT1/PTEN alterations. A literature search was conducted using PubMed and MEDLINE databases, published abstracts, and studies from ClinicalTrials.gov between 2003 and February 2024. Keywords included capivasertib, AZD5363, PI3K/AKT/mTOR pathway, and breast cancer. All applicable publications, package inserts, meeting abstracts, and clinical trials with capivasertib were reviewed. Capivasertib is a first-in-class inhibitor of 3 isoforms of AKT (AKT-1, AKT-2, and AKT-3) which is an essential component in the PI3K/AKT/mTOR signaling pathway involved in oncogenesis. In the phase III CAPItello-291 trial, capivasertib in combination with fulvestrant (C+F) demonstrated improved progression-free survival (PFS) (7.3 vs 3.1 months) compared with placebo-fulvestrant (P+F) cohort in AKT-altered pathway patients who had progressed through prior aromatase inhibitor. The most common adverse reactions of any grade reported in the C+F group were diarrhea, cutaneous skin reactions, nausea, fatigue, and vomiting. HR+/HER2- advanced breast cancer patients experience progression following endocrine therapies and cyclin-dependent kinase (CDK) 4/6 inhibitors. Capivasertib is a viable treatment option for patients with PIK3CA/AKT1/PTEN activating mutations following progression on endocrine-based regimens in the metastatic setting or recurrence within 12 months of completing adjuvant therapy. Integration of capivasertib into clinical practice is ongoing; intermittent dosing and favorable toxicity are attractive for future novel combination prospective trials.

Prognostic impact of limited resection vs. inadequate adjuvant therapy in patients with pathologic stage II or III non-small cell lung cancer: results from the Korean Association of Lung Cancer Registry.

For patients with stage II and III non-small cell lung cancer (NSCLC), various multi-modality treatments are required. However, depending on the individual conditions of patients, there will be a significant difference in prognosis. Therefore, this study investigated the clinical impact of inadequate treatment (limited surgery and inadequate adjuvant therapy) in patients with NSCLC stage II or III using data from the Korean Association of Lung Cancer Registry (KALC-R) between 2014 and 2016. Of the 8,110 new lung cancer cases registered at the Korea Central Cancer Registry in 2014-2016, 721 patients with stage II or III NSCLC were selected and divided into three groups according to differences in cancer treatment methods. In group A, patients underwent standard surgery and completed adjuvant therapy. In group B, patients underwent standard surgery without completing adjuvant therapy. In group C, patients received adjuvant therapy after limited surgery. After performing propensity score matching (PSM) for selected patients, overall survival (OS) and disease-free survival (DFS) rates of the three groups of patients with stage II and III NSCLC patients were then compared. Of the 721 patients with NSCLC, 239, 437, and 45 belonged to groups A, B, and C, respectively. After 1:3 PS matching for groups B and C, the 5-year survival rate of patients with stage II or III NSCLC were 68.0% and 26.7% for groups B and C, respectively and the DFS rate was 59.1% and 16.2% for groups B and C, respectively. The therapeutic effect of the standard surgery was the best. Although patients received adjuvant therapy, limited resection resulted in a poorer prognosis in compromised patients compared with omitting adjuvant therapy followed by standard surgery. Thus, surgical treatment should be considered in patients who are unable to complete surgical and adjuvant therapy.

Capivasertib: First Approval.

Capivasertib (Truqap™) is an orally available, small-molecule pan-AKT inhibitor being developed by AstraZeneca for the treatment of various cancers, including breast and prostate cancers. Capivasertib received its first approval, in the USA, in November 2023 for use in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor2 (HER2)-negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12months of completing adjuvant therapy. Capivasertib is also under regulatory review for HR-positive, HER2-negative breast cancer in the EU and several other countries, and in phaseIII clinical development for use (in combination with other anti-cancer agents) in the treatment of triple-negative breast cancer, castration-resistant prostate cancer, and hormone-sensitive prostate cancer. This article summarizes the milestones in the development of capivasertib leading to this first approval for HR-positive, HER2-negative, locally advanced or metastatic breast cancer.

Capivasertib (Truqap) for breast cancer.

The oral kinase inhibitor capivasertib (Truqap – AstraZeneca), a first-in-class AKT inhibitor, has been approved by the FDA for use in combination with the selective estrogen receptor degrader (SERD) fulvestrant (Faslodex, and generics) for treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer in adults with one or more PIK3CA/AKT1/PTEN-alterations who had disease progression on at least one endocrine-based regimen for metastatic disease or recurrence on or within 12 months of completing adjuvant therapy.

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy

ImportanceAcral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma. ObjectiveTo determine the efficacy of adjuvant PD1 in resected AM or MM. DesignAn international, retrospective cohort study SettingData up to November 2021 collected from 20 centres across 10 countries. ParticipantsOne hundred and ninety four patients with resected stage III or IV1 AM or MM who received adjuvant PD1 were included and compared to matched patients from the Melanoma Institute Australia (MIA) database using a propensity score matching analysis. Main outcomes and measuresRecurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) were investigated. ResultsForty five of 139 (32%) AM and 9 of 55 (16%) MM patients completed adjuvant therapy. The main reason for early treatment cessation in both groups was disease recurrence: 51 (37%) and 30 (55%) in the AM and MM groups, respectively. In the AM group adjuvant PD1 was associated with a longer RFS [HR-0.69 (0.52–0.92, p = 0.0127)], DMFS [HR0.58 (0.38–0.89, p = 0.0134)] and OS [HR of 0.59 (0.38–0.92, p-value 0.0196)] when compared to the historical cohort. In the MM group there was no statistical difference in RFS [HR1.36 (0.69–2.68,p-value 0.3799], DMFS or OS. Conclusion and relevanceAfter adjuvant PD1, both AM and MM have a high risk of recurrence. Our data suggests a benefit to using adjuvant PD1 therapy in resected AM but not in resected MM. Additional studies to investigate the efficacy of adjuvant PD1 for MM are needed.

Early identification and treatment of occult metastatic disease in stage III colon cancer (SU2C ACT3 clinical trial).

148 Background: Despite adjuvant chemotherapy, nearly 30% of patients with Stage III colon cancer (CC) will recur. We are performing a randomized clinical trial using a plasma-only circulating tumor DNA (ctDNA) platform after adjuvant therapy for patients with ctDNA-positive Stage III CC. Methods: Patients (pts) with Stage III CC are eligible for prescreening, including tumor tissue profiling by next-generation sequencing. Pts are screened 3-6 weeks after adjuvant chemotherapy. At screening blood is collected for ctDNA analysis with a CLIA-certified sequencing panel (Reveal, Guardant Health). A baseline CT scan is required to confirm lack of metastases. Pts with undetectable ctDNA (-) at screening undergo surveillance with imaging, labs and ctDNA testing every 3 months (Arm 3). ctDNA-detectable (+) pts who are biomarker-negative are randomized to 1:1 to FOLFIRI (Arm 1) or active surveillance (Arm 2). ctDNA+ pts with an actionable biomarker (biomarker-positive) are given 6 months biomarker-directed therapy as follows: V600E/MSS- encorafenib, binimetinib and cetuximab (Arm 5), HER2 amplified trastuzumab/pertuzumab (arm 6), and MSI-H nivolumab (Arm 4). Primary outcome is ctDNA clearance in Arms 1 and 2, 1-month after completion of additional adjuvant therapy or surveillance. Secondary outcomes include RFS and OS in Arms 1 and 2, ctDNA clearance and RFS/OS in the other arms. An interim analysis is planned after 13 patients are enrolled in Arm 1 and primary outcome will be assessed after 50 patients’ complete treatment/surveillance in Arms 1 and 2. Results: From 4/16/2020 through 9/8/2023, 147 patients were screened, 66 screen failed. Pre-screening as well as active ongoing enrollment is underway. To date, 73 patients have enrolled (46 male and 27 female). 53 (72.6%) were white. 10 (13.7%) patients were noted to be ctDNA+ within 6 weeks of completion of adjuvant therapy: 4 in Arm 1; 5 in Arm 2; 1 in Arm 4. 63 pts were ctDNA- and in Arm 3. Conclusions: In this ctDNA guided trial, with single time-point testing, only 13.7% of pts were ctDNA+ after adjuvant chemotherapy. 90% of ctDNA+ patients did not have an actionable biomarker. Strict windows for eligibility and enrollment initially restricted eligibility but these were adjusted to increase eligibility. To mitigate the low positivity rate and allow us to meet our accrual goals in arm 1 and 2, the protocol was amended to allow for entry into the ctDNA+ arms at any time during the first 3 years after completion of adjuvant therapy as opposed to within 6 weeks of completion of adjuvant therapy. The lessons learnt would have implications for other ctDNA-driven clinical trials. Clinical trial information: NCT03803553. Patient distribution in the SU2C ACT3 study. Total Screened Pre-Screening Screen Fail Enrolled Off Study ctDNA Treatment Arm + - Arm 1 Arm 2 Arm 3 Arm 4 Arm 5 Arm 6 147 8 66 73 10 10 63 4 5 63 1 0 0

Utilization of tissue-free minimal residual disease testing in colorectal cancer patients from Asia and Middle East.

The presence of minimal residual disease (MRD) after curative-intent surgery for early-stage cancers is associated with disease recurrence. Circulating tumour deoxyribonucleic acid (ctDNA) has emerged as a promising biomarker for MRD assessment in patients with colorectal cancer (CRC) who have undergone surgery or completed adjuvant therapy. MRD tests are already available for use in clinics; however, treatment decisions following MRD results obtained in routine practice are infrequently described. In this observational study, we report on the real-world clinical use of Guardant Reveal, a validated tissue-free MRD assay, in the first 215 consecutive patients (279 samples) with CRC tested in Asia and the Middle East. Overall, 22% of patients had ctDNA detected in their first MRD test, and the frequency of ctDNA positivity increased with increasing tumour stage. 132 samples were tested with an earlier version of Guardant Reveal, one that assessed both genomic and epigenomic features. An updated version of the assay assesses only ctDNA methylation data and was used for the remaining 147 samples. In patients with stage II CRC, 71% of tests were ordered within 12 weeks after tumour resection, while for patients with stage III disease, 69% of tests were ordered after completion of all curative-intent treatment. Clinical cases utilizing tissue-free MRD assessment are described.

Contralateral prophylactic mastectomy: Weighing the risks of delayed chemotherapy, radiotherapy, and hormonal therapy

Many patients with unilateral breast cancer opt for contralateral prophylactic mastectomy (CPM) at the time of therapeutic mastectomy (immediate CPM) or following completion of adjuvant therapy. Studies show that immediate CPM increases the risk of surgical complications related to unilateral mastectomy (UM) alone, which may lead to delays in adjuvant therapy initiation. However, it is unclear if these complications cause clinically significant delays in initiating adjuvant chemotherapy, radiotherapy, or hormonal therapy. A retrospective chart review was conducted on patients with breast cancer who underwent immediate CPM versus UM alone at Columbia University Medical Center from January 2000 to December 2020. Patient demographic and oncologic characteristics; complications; and timing of adjuvant chemotherapy, radiotherapy, and/or hormonal therapy relative to therapeutic mastectomy were collected. In this study, 239 UM alone patients were propensity score matched to 239 immediate CPM patients. No significant difference in complication rates was found between the index and contralateral breasts in CPM patients. A similar percentage of CPM and UM patients experienced postoperative complications (19% vs. 17%, p = 0.64). No significant difference in time to adjuvant chemotherapy, radiotherapy, or hormonal therapy was found between CPM patients with complications and all CPM patients or all UM patients. There is a lack of clear guidance for clinical decision-making regarding timing of CPM relative to adjuvant therapy. Our study suggests that immediate CPM does not significantly increase the risks of postoperative complications or complication-related delays in the initiation of adjuvant chemotherapy, radiotherapy, or hormonal therapy. This information may help patients and providers to plan, select, and schedule breast cancer treatment options.

Fate of de-functioning ileostomy after left colon and rectal cancer resection: observation from a single unit of a cancer hospital.

Background: De-functioning ileostomy (DS) has been shown to reduce rate of anastomotic leak after left colon and rectal cancer resection and can avoid consequences of leak with its morbidity and possible mortality. Externalisation of bowel is not easily appreciated; patients always inquire about the timing of closure and not all stomas are closed. The aim of the study is to assess the timing of stoma closure and the reasons for stoma becoming permanent. Methods: Patients who underwent surgery for left colon and rectal cancer with de-functioning stoma from April 2019 to May 2022 in single unit of Bhaktapur Cancer Hospital, were assessed regarding timing of stoma closure. We have made a policy of stoma closure after completion of adjuvant therapy. De-functioning stoma that was not reversed at follow up were assessed regarding reason for it becoming permanent. Results: Forty-two patients underwent de-functioning stoma during the study period; 30 after rectal resection, 2 after pouch creation, 6 after anterior resection and 4 after left hemicolectomy. Twenty-eight (77%) stomas were closed, 5 are receiving adjuvant treatment. Closure was not done in 8 patients; 5 due to recurrence of disease; 1 due to patient wish, 2 deaths occurred prior to closure, one due to COVID-19 and another due to acute myocardial infraction. One patient with multiorgan resection died within 30 days of surgery due to other medical cause. The median time of stoma closure after completion of adjuvant treatment is 8 weeks, IQR (7-10). Patients had to stay with stoma for a median period of 6months, IQR (5-8). The median time for discharge after stoma reversal is 9 days, IQR (7-10). There were 4 Grade II Clavien-Dindo complications after stoma closure. Conclusion: Seventy- seven percent of patients with DS underwent closure in our series. Recurrence was the most common cause for it becoming permanent.

Circulating Tumour DNA as Biomarker for Colorectal Liver Metastases: A Systematic Review and Meta-Analysis.

Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver metastases (CRLM). A systematic search was conducted in electronic databases for studies published prior to the 26th of May 2023. Studies investigating the association between ctDNA and oncological outcomes in patients undergoing curative-intent local therapy for CRLM were included. Meta-analyses were performed to pool hazard ratios (HR) for the recurrence-free survival (RFS) and overall survival (OS). A total of eleven studies were included and nine were eligible for meta-analyses. Patients with detectable ctDNA after surgery experienced a significantly higher chance of recurrence (HR 3.12, 95% CI 2.27-4.28, p < 0.000010) and shorter OS (HR 5.04, 95% CI 2.53-10.04, p < 0.00001) compared to patients without detectable ctDNA. A similar association for recurrence was found in patients with detectable ctDNA after the completion of adjuvant therapy (HR 6.39, 95% CI 2.13-19.17, p < 0.0009). The meta-analyses revealed no association between detectable ctDNA before surgery and the RFS and OS. These meta-analyses demonstrate the strong association between detectable ctDNA after treatment and oncological outcomes in CRLM patients.

1023 The Changing Indication and Outcomes of Patients Undergoing Pancreatectomy for Malignancy

Abstract Aim Pancreatic surgery has evolved significantly in terms of indications and peri-operative management to improve long term outcomes for patients. The aim of this study is to assess the change in indication and long-term outcome for patients undergoing pancreatectomy for malignancy. Method Patients who underwent pancreatectomy at the West of Scotland Pancreatic Unit, Glasgow Royal Infirmary between 2000 – 2020 for malignancy were included. Clinicopathological variables, survival and recurrence data were collected from patient notes and electronic patient records. Results 594 patients were identified. The majority were for pancreatic ductal adenocarcinoma (PDAC) n = 325 (54.7%). There was a significant increase in overall survival for all indications (28.6 months vs 41.8 months, P = 0.001), completion of adjuvant therapy and the use of neoadjuvant therapy (P&amp;lt;0.001) over the first and second decades in the study period. After adopting a neoadjuvant strategy for PDAC in the unit from 2013, the overall median survival increased from 24.6 months to 34.5 months (P&amp;lt;0.001). The overall survival for PDACs was higher for those receiving neoadjuvant chemotherapy compared to upfront resection (41.9 months vs 38.9 months, P = 0.151). For patients with PDAC who received upfront surgery, median survival increased from 24.2 to 40.3 months (P = 0.004) once a neoadjuvant strategy was adopted. Conclusions There has been significant changes to the indications and long-term outcomes for patients undergoing pancreatectomy. A neoadjuvant strategy improved survival even in those patients who received upfront surgery.

Camrelizumab in combination with doxorubicin, cisplatin, ifosfamide, and methotrexate as neoadjuvant therapy for osteosarcoma: A single-arm, exploratory phase II trial.

11526 Background: Tumor necrosis rate after neoadjuvant therapy is one of the strongest predictors of long-term outcome for patients with osteosarcoma. Patients with good response (tumor necrosis rate ≥90%) have a substantially better survival than those with poor response (tumor necrosis rate &lt; 90%), with 5-year overall survival of 75-80% and 55-65%, respectively. However, treatments for osteosarcoma have not yet shown much progress since the introduction of perioperative chemotherapy in 1970s. New neoadjuvant combinations are required to explored for osteosarcoma. Methods: In this phase II trial (NCT04294511), patients aged 14-65 years with histopathologically confirmed osteosarcoma and Eastern Cooperative Oncology Group performance status of 0-1 received three 21-day cycles of neoadjuvant regimen (camrelizumab 200 mg on day 1 of each cycle; doxorubicin 37.5 mg/m2 or liposomal doxorubicin 25 mg/m2 on days 1-2 of cycles 1 and 3; cisplatin 100 mg/m2 on day 2 of cycles 1 and 3; methotrexate 8-12 g/m2 on day 12 of cycle 1; and ifosfamide 3 g/m2 on days 1-4 of cycle 2). Surgery was scheduled 12-14 days after neoadjuvant therapy. Two weeks after surgery, patients received 6 cycles of adjuvant therapy (camrelizumab 200 mg on day 1 of each cycle; doxorubicin 37.5 mg/m2 or liposomal doxorubicin 25 mg/m2 on days 9-10 of cycles 1, 3, and 5; cisplatin 100 mg/m2 on day 10 of cycles 1, 3, and 5; methotrexate 8-12 g/m2 on day 2 of cycles 1, 3, and 5; and ifosfamide 3 g/m2 on days 1-4 of cycles 2, 4, and 6). The primary endpoint was good response (tumor necrosis rate ≥90%) rate after neoadjuvant therapy. Results: A total of 86 patients were screened and 75 patients signed informed consent from December 2019 to June 2022. By the data cutoff date on December, 2022, 8 patients did not complete neoadjuvant therapy and 2 patients refused surgery. 65 patients completed neoadjuvant therapy, one patient had disease progression before surgery, 64 received surgical resection and adjuvant therapy, and 44 completed adjuvant therapy. Thirty-one (48.4%, 95%CI: 36.6%-60.4%) of 64 patients showed good response. The most common grade 3-4 adverse events were decreased platelet count (44.0%), decreased white blood cell (37.3%), decreased neutrophil count (29.3%), oral mucositis (14.7%), increased alanine aminotransferase (12.0%), and increased aspartate aminotransferase (10.7%). Conclusions: Camrelizumab combined with doxorubicin, cisplatin, methotrexate and ifosfamide in the perioperative treatment of osteosarcoma patients were safe and tolerable. Postoperative good response rate was similar to previously reported results. Survival follow-up is still ongoing to analyze the effect of perioperative immunotherapy combined with chemotherapy on long-term outcomes of patients with osteosarcoma. Clinical trial information: NCT04294511 .

Clinical Efficacy of Neoadjuvant Chemotherapy with Gemcitabine plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma Compared with Upfront Surgery.

The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear. In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 <500U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS. Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02). NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC.