Peking University Cancer Hospital Research Articles

The relevance of dental management prior to radiation therapy with severe oral mucositis in head and neck cancer patients

Background/purposeDental management prior to radiotherapy is often time-critical, and there are no studies on whether manipulations such as tooth extraction influence the risk of severe radiation-induced oral mucositis (ROM) during radiotherapy. Therefore, the aim of this study was to describe the relationship between dental management and the incidence of severe ROM. Materials and methodsA retrospective analysis was conducted on 144 head and neck cancer (HNC) patients who received dental management before radiotherapy at Peking University Cancer Hospital, from January 2016 to December 2017. Demographic characteristics, primary tumor features, cancer treatment characteristics, and severity of oral mucositis during radiotherapy were recorded. Univariate analysis and logistic regression analysis were used to explore factors associated with severe radiation-induced oral mucositis. ResultsThe incidence of grade 3 mucositis was 14.5% (22/144); univariate analysis showed that the number of extracted teeth (OR = 1.313; 95%CI = 1.012–1.702; P = 0.040) and patients with primary oral cancer had a higher risk of developing grade 3 mucositis (OR = 3.848; 95% CI = 1.508–9.822; P = 0.005). No statistical correlation was found between pre-radiation therapy prophylaxis, dental restoration, endodontic treatment, and grade 3 mucositis (P > 0.05). Logistic regression analysis showed that the number of extracted teeth (OR = 1.421, 95%CL = 1.071–1.885, P = 0.015) and primary tumor location in the oral cavity (compared with other head and neck cancers) (OR = 5.165, 95%CL = 1.636–16.311, P = 0.005) were significantly associated with grade 3 mucositis. ConclusionIn HNC patients undergoing radiotherapy, the primary site located in the oral cavity and a higher number of teeth extracted are independent risk factors for the development of severe mucositis.

Abemaciclib plus endocrine therapy versus chemotherapy after progression on prior palbociclib in HR+/HER2- metastatic breast cancer: A single center real-world study in China.

Cyclin-dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard-of-care for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib-based ET in Chinese patients with HR+/HER2- MBC. From 414 consecutive patients with HR+/HER2- MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease-free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression-free survival (PFS) compared using the Kaplan-Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group. The median PFS was 6.0 months (95% confidence interval [CI]: 3.94-8.06) in abemaciclib group and 4.0 months (95% CI, 2.52-5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first-line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd-line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069). Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2- MBC after progression on prior palbociclib-based therapy in addition to chemotherapy.

Short- and long-term post-nephrectomy outcomes for retroperitoneal liposarcoma from a high-volume sarcoma center: a propensity score matching analysis.

Multivisceral en bloc resection with the ipsilateral kidney is commonly performed in patients with retroperitoneal liposarcoma (RLPS). We evaluated the effect of nephrectomy on short- and long-term outcomes in patients with RLPS. Data from a prospectively maintained database of the Peking University Cancer Hospital Sarcoma Center between April 2011 and August 2022 were analyzed. We classified the RLPS patients who underwent surgery into nephrectomy group (NP) and non-nephrectomy group (non-NP). Patients were matched using a 1:1 propensity score to eliminate baseline differences between groups. Postoperative renal function outcomes, major morbidity, and mortality were analyzed to compare short-term outcomes after nephrectomy. Differences in local recurrence-free survival (LRFS) and overall survival (OS) were compared by Kaplan-Meier analysis with respect to oncological benefits. In the matched cohort, patients in the NP group had significantly higher postoperative eGFR and CKD stages, but none required dialysis. Patients between NP and non-NP had a comparable major morbidity (p = 0.820) and 60-day mortality (p = 0.475). Patients in the NP group had a higher 5-year LRFS rates than those in the non-NP group (34.5 vs. 17.8%, p = 0.015), and similar 5-year OS rates (52.4 vs. 47.1%, p = 0.401). Nephrectomy was an independent risk factor for LRFS, but not for major morbidity or OS. RLPS resection with nephrectomy is related to a mild progression of renal impairment; however, dialysis is rare. En bloc nephrectomy for complete resection of RLPS is safe and improves local control.

Considerations for multidisciplinary management of synchronous primary breast cancer and primary lung cancer - Analysis of thirty-one patients.

The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and "chaotic". In the present study we discuss the management strategy for this group of patients. We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)-CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. Routine chest CT is needed for breast cancer patients before surgery, and PET-CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer.

Clinical significance of postoperative folate receptor-positive circulating tumor cells (FR + CTCs) for long-term prognosis in patients with invasive adenocarcinoma (IAC) of the lung.

The aim of the study was to evaluate the prognostic value of postoperative folate receptor-positive circulating tumor cell (FR + CTC) detection in patients with stage I-III invasive adenocarcinoma (IAC) treated with surgery. Patients with lung adenocarcinoma (LUAD) who underwent surgical resection in Peking University Cancer Hospital and received postoperative FR + CTC analysis from July 2016 to January 2021 were retrospectively collected. Comparisons between or among groups were made using the Kruskal-Wallis or Mann-Whitney U tests. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression analyses were performed to explore the factors predicting recurrence and survival. There were significant differences between the high and low groups in terms of age (p = 0.002), postoperative CA199 (p = 0.038), and postoperative SCC (p = 0.024). There were no significant differences in the other indicators (all p>0.05). N stage 1, N stage 2, and neoadjuvant therapy (NAT) were independent risk factors for disease recurrence and death; pleural invasion (PI), and nerve invasion were independent risk factors for death. The Kaplan-Meier curve showed a notable trend for a worse disease-free survival (DFS) or overall survival (OS) for patients with high levels of FR + CTCs in our study, but none of these were statistically significant. The detection of FR + CTCs postoperatively was an independent predictor of recurrence in patients treated for stage I-III IAC. Standardized detection methods and optimal time points for assessment should be established in future studies.

Abstract 5029: VAF in ctDNA correlated with advanced breast cancer tumor burden and prognosis

Abstract Purpose: In patients with first-line advanced breast cancer (ABC), the correlation between ctDNA variant allele frequency (VAF) and tumor disease burden, and its prognostic value remains poorly investigated. Methods: This study included patients with ABC diagnosed at Peking University Cancer Hospital who performed ctDNA test before receiving first-line treatment. Baseline plasma samples were collected for assessing ctDNA alterations and VAF with next-generation sequencing. The sum of tumor target lesion diameters (SLD) was measured with imaging methods according to RECIST 1.1 criteria. Results: The final cohort included 184 patients. The median age of the cohort was 49.4 (IQR: 42.3-56.8) years. The median VAF was 15.6% (IQR: 5.4%-33.7%). VAF showed positive correlation with SLD in patients with relatively large tumor lesions (r = 0.314, p = 0.003), but not in patients with small tumor lesion (p = 0.226). VAF was associated with multiple metastasis sites (p = 0.001). Multivariate Cox regression analysis showed that high VAF was associated with shorter overall survival (OS) (HR: 3.519, 95% confidence interval (CI): 2.149-5.761), and first-line progression-free survival (PFS) (HR: 2.352, 95%CI: 1.462-3.782). Conclusion: ctDNA VAF associated with tumor disease burden, and was a prognostic factor for patients with ABC. A combination of ctDNA test and radiographic imaging might enhance tumor burden evaluation, and improve prognosis stratification in patients with ABC. Citation Format: Jianxin Zhong, Huiping Li, Bin Shao, Hanfang Jiang, Xiaoran Liu, Haoran Tang, Shidong Jia. VAF in ctDNA correlated with advanced breast cancer tumor burden and prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5029.

A real-world study of treatment patterns following disease progression in epithelial ovarian cancer patients undergoing poly-ADP-ribose polymerase inhibitor maintenance therapy

BackgroundThe efficacy of subsequent therapy after poly-ADP-ribose polymerase (PARP) inhibitor maintenance treatment has raised concerns. Retrospective studies show worse outcomes for platinum-based chemotherapy after progression of PARP inhibitor-maintenance therapy, especially in BRCA-mutant patients. We aimed to describe subsequent therapy in ovarian cancer patients after PARP inhibitor-maintenance therapy and evaluate their response to treatment. We focused on chemotherapy for patients with a progression-free interval (PFI) of ≥ 6 months after prior platinum treatment, based on BRCA status.MethodsWe analyzed real-world data from Peking University Cancer Hospital, subsequent therapy after progression to PARP inhibitor-maintenance therapy for epithelial ovarian cancer between January 2016 and December 2022. Clinicopathological characteristics and treatment outcomes were extracted from medical records. The last follow-up was in May 2023.ResultsA total of 102 patients were included, of which 29 (28.4%) had a germline BRCA1/2 mutation and 73 (71.6%) exhibited BRCA1/2 wild-type mutations. The PARP inhibitors used were Olaparib (n = 62, 60.8%), Niraparib (n = 35, 34.3%), and others (n = 5, 4.9%). The overall response rate (ORR) was 41.2%, and the median time to second progression (mTTSP) was 8.1 months (95%CI 5.8–10.2). Of 91 platinum-sensitive patients (PFI ≥ 6 months) after progression to PARP inhibitor-maintenance therapy, 65 patients subsequently received platinum regimens. Among them, 30 had received one line of chemotherapy before PARP inhibitor-maintenance therapy. Analysis of these 30 patients by BRCA status showed an ORR of 16.7% versus 33.3% and mTTSP of 7.1 (95% CI 4.9–9.1) versus 6.2 months (95% CI 3.7–8.3, P = 0.550), for BRCA-mutant and wild-type patients, respectively. For the remaining 35 patients who had received two or more lines of chemotherapy before PARP inhibitor-maintenance therapy, ORR was 57.1% versus 42.9%, and mTTSP was 18.0 (95% CI 5.0–31.0) versus 8.0 months (95% CI 4.9–11.1, P = 0.199), for BRCA-mutant and wild-type patients, respectively.ConclusionNo differences in survival outcomes were observed among patients with different BRCA statuses. Furthermore, for patients who had undergone two or more lines of chemotherapy before PARP inhibitor maintenance therapy, no negative effects of PARP inhibitors on subsequent treatment were found, regardless of BRCA status.

An ultrasound-based nomogram for predicting axillary node pathologic complete response after neoadjuvant chemotherapy in breast cancer: Modeling and external validation.

The staging and treatment of axillary nodes in breast cancer have become a focus of research. For breast cancer patients with fine-needle aspiration-or core needle biopsy-confirmed positive nodes, axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is still a standard treatment. However, some patients achieve an axillary pathologic complete response (pCR) after NAC. In this study, the authors sought to construct a model to predict axillary pCR in patients with positive axillary lymph nodes (cN+) breast cancer. Data from patients with pathologically proven cN+ breast cancer treated with NAC followed by ALND between January 2010 and April 2019 at the Peking University Cancer Hospital were reviewed. Axillary lymph node status was assessed using ultrasonography before and after NAC. The patient cohort was assigned to the construction and internal validation cohorts according to admission time. A nomogram was constructed based on the significant factors associated with axillary pCR. The predictive performance of the model was externally validated using data from Peking University First Hospital. This study included 953 and 267 patients from Peking University Cancer Hospital and Peking University First Hospital, respectively. In the construction cohort, 39.7% (238 of 600) of patients achieved axillary pCR after NAC. The result of multivariate logistic regression analysis showed that tumor grade, clinical nodal response, NAC regimen, tumor pCR, lymphovascular invasion, and tumor biologic subtype were significant independent predictors of ypN0 (p < 0.05). The areas under the receiver operating characteristic curves for the construction, validation, and independent testing cohorts were 0.87 (95% confidence interval [CI], 0.84-0.90), 0.83 (95% CI, 0.79-0.87), and 0.84 (0.79-0.89), respectively. A nomogram was constructed to predict the pCR of axillary lymph nodes after NAC for breast cancer. Validation of both the internal and external cohorts achieved good predictive performance, indicating that the model has preliminary clinical application prospects.

Total Neoadjuvant Therapy With PD-1 Blockade for High-Risk Proficient Mismatch Repair Rectal Cancer

Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown. To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy. This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022. Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine. The primary end point was pathologic complete response rate. Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy. This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

Natural history of bone-only metastasis in renal cell carcinoma

BackgroundBone metastasis (BM) is considered a poor prognostic factor of renal cell carcinoma (RCC). Confusion exists regarding how to deal with RCC patients with bone-only metastasis. Patients and MethodsThe clinical data of consecutive RCC patients with bone-only metastasis at Peking University Cancer Hospital between 2006 and 2018 were retrospectively collected and analyzed. ResultsFifty-four eligible patients were screened from an RCC database of 1,878 metastatic patients. After a median follow-up of 43.6 m, 61.1% of the patients were presented with progression of prior BM or new BM. The progression-free survival (PFS) and overall survival (OS) was 16.2 m (95%CI: 11.4–21.0) and 65.2 m, respectively. For the 30 patients with oligo-metastasis (≤3 loci) and 24 ones with multiple-metastasis (>3 loci), the median OS was not reached and 42.0m (95%CI: 12.7–71.2) with statistical difference (P < 0.001). In the oligo-metastasis group, the median PFS of the 15 patients treated with local therapy and of the 13 patients treated with systemic therapy was 14.2 m (95%CI: 5.3–23.3) and 18.0 m (95%CI:15.4–20.6), respectively. In the multiple-metastasis group, the median PFS and OS of the 18 patients treated with systemic therapy was 16.6 m (95%CI: 7.5–25.7) and 63.9 m (95%CI: 21.8–106.0), respectively. Univariate analysis and multivariate analysis showed that the number of metastatic sites (oligo/multiple) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score, RCC pathological subtype were significantly associated with prognosis (P < 0.05). ConclusionRCC patients with bone-only metastases have a favorable prognosis. The number of metastatic sites, IMDC, RCC pathological subtype could serve as survival predictors, which might provide clue of treatment modality.

PTCH1 mutation as a potential predictive biomarker for immune checkpoint inhibitors in gastrointestinal cancer.

Immune checkpoint inhibitors (ICIs) have become prominent therapies for gastrointestinal cancer (GC). However, it is urgent to screen patients who can benefit from ICIs. Protein patched homolog 1 (PTCH1) is a frequently altered gene in GC. We attempt to explore the association between PTCH1 mutation and immunotherapy efficacy. The MSKCC cohort (n = 236) with GC (esophageal, gastric and colorectal cancers) patients receiving ICIs was used for discovery and the Peking University Cancer Hospital (PUCH) GC cohort (n = 92) was used for validation. Overall survival (OS) and tumor mutational burden (TMB) of the PTCH1 mutant-type (PTCH1-MUT) and PTCH1 wild-type (PTCH1-WT) groups were compared. Furthermore, GC data were collected from TCGA to assess the potential mechanisms. In the MSKCC cohort, PTCH1-MUT group showed significantly better OS (P = 0.017) and higher TMB. Multivariate analysis showed that PTCH1 mutation was associated with better OS. In the PUCH cohort, PTCH1-MUT group showed significantly longer OS (P = 0.036) and PFS, and higher DCB and TMB. Immune cell infiltration analysis revealed that PTCH1-MUT group had significantly higher distributions of CD8 T cells, CD4 T cells, NK cells, mast cells, and M1 cells. The PTCH1-MUT group showed significantly higher expression of most immune- related genes. GSEA showed that the PTCH1-MUT group had enriched INF-γ response, INF-α response, glycolysis, and reactive oxygen species pathway gene sets. PTCH1 mutation may represent a potential biomarker for predicting ICIs response in GC. Nevertheless, prospective cohort studies should be performed to further validate our results.

Dietary habits and nutrition status in esophageal cancer patients after esophageal reconstruction.

Surgery is the cornerstone of the treatment of esophageal cancer (EC). This study is to evaluate the dietary habits and nutrition status in EC patients who underwent esophagectomy followed by esophageal reconstruction. This retrospective study included patients with EC who underwent esophagectomy followed by esophageal reconstruction in the Department of Thoracic Surgery I of Peking University Cancer Hospital between February 2014 and December 2018. The primary outcomes were dietary habits and nutrition status. The secondary outcomes were gastrointestinal symptoms and quality of life (QoL). A total of 346 patients were included. At 30 months after the operation, 90.2% of the patients had recovered to regular dietary habits, 72.8% of patients had a restored frequency of preoperative regular food intake, 2.3% of the patients ate more than six times a day, and 0.6% had semi-liquid food because of bad teeth. The nutrition status remained stable after 6 months postoperatively and recovered slightly 1 year after the surgery. At 30 months after the operation, the most common gastrointestinal symptoms were reflux (38.4%), dysphagia (15.3%), hoarseness (11.8%), abdominal distension (6.6%), diarrhea (2.9%), and nausea and vomiting (2.3%). According to the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-OG 25 (EORTC QLQ-OG 25), the factors that affected the life quality of patients during follow-up were anxiety, reflux, and dietary limitations. Most patients with EC who underwent esophageal reconstruction recovered to regular dietary habits and stable nutrition status, while some may still suffer from gastrointestinal symptoms, anxiety, and dietary limitations.

Variant allele frequency in circulating tumor DNA correlated with tumor disease burden and predicted outcomes in patients with advanced breast cancer

PurposeIn patients with first-line advanced breast cancer (ABC), the correlation between ctDNA variant allele frequency (VAF) and tumor disease burden, and its prognostic value remains poorly investigated.MethodsThis study included patients with ABC diagnosed at Peking University Cancer Hospital who performed ctDNA test before receiving first-line treatment. Baseline plasma samples were collected for assessing ctDNA alterations and VAF with next-generation sequencing. The sum of tumor target lesion diameters (SLD) was measured with imaging methods according to RECIST 1.1 criteria.ResultsThe final cohort included 184 patients. The median age of the cohort was 49.4 (IQR: 42.3–56.8) years. The median VAF was 15.6% (IQR: 5.4%-33.7%). VAF showed positive correlation with SLD in patients with relatively large tumor lesions (r = 0.314, p = 0.003), but not in patients with small tumor lesions (p = 0.226). VAF was associated with multiple metastasis sites (p = 0.001). Multivariate Cox regression analysis showed that high VAF was associated with shorter overall survival (OS) (HR: 3.519, 95% confidence interval (CI): 2.149–5.761), and first-line progression-free survival (PFS) (HR: 2.352, 95%CI: 1.462–3.782). Combined VAF and SLD improved prediction performance, both median OS and PFS of patients in VAF(H)/SLD(H) group were significantly longer than VAF(L)/SLD(L) group (mOS: 49.3 vs. 174.1 months; mPFS: 9.6 vs. 25.3 months).ConclusionctDNA VAF associated with tumor disease burden, and was a prognostic factor for patients with ABC. A combination of ctDNA test and radiographic imaging might enhance tumor burden evaluation, and improve prognosis stratification in patients with ABC.

The differential diagnosis of lung precursor glandular lesions, micro-invasive adenocarcinoma, and invasive adenocarcinoma using low dose spectral computed tomography perfusion imaging.

Few studies about the association between computed tomography (CT) perfusion imaging parameters and invasiveness in lung adenocarcinoma (LUAD) have been conducted using low dose spectral CT perfusion imaging. The purpose of this study was to investigate application of spectral revolution CT low-dose perfusion imaging in the differential diagnosis of different pathological subtypes of LUAD. This was a cross-sectional study based on historical data from January 2018 to May 2019 in Peking University Cancer Hospital & Institute. A total of 62 cases were enrolled, including 2 cases of atypical adenomatous hyperplasia (AAH), 3 cases of adenocarcinoma in situ (AIS), 4 cases of minimally invasive adenocarcinoma (MIA), and 53 cases of invasive adenocarcinoma (IAC), all confirmed with pathology. The inclusion and exclusion criteria were regulated. Using Revolution low-dose CT perfusion imaging (GE, USA), the CT perfusion parameters of hemodynamics were obtained: blood flow (BF), blood volume (BV), impulse residue function time of arrival (IRF TO), maximum slope of increase (MSI), mean transit time (MTT), permeability surface area product (PS), positive enhancement integral (PEI), and maximum enhancement time (Tmax). Univariate analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare the differences of CT perfusion quantitative parameters among AAH, AIS, MIA, and IAC. Mann-Whitney test was used to compare the difference of CT perfusion imaging parameters between preinvasive lesions (AAH and AIS) and invasive lung cancer (MIA and IAC). Statistically significant differences in IRF TO were observed in LUAD with different invasiveness, namely, among AIS, MIA, and IAC groups (0.56±0.74 vs. 0.54±1.08 vs. 4.39±2.19, P=0.004). Statistically significant differences in IRF TO were also observed between pre-invasive lesions group (AAH and AIS) and invasive lung cancer group (MIA and IAC) (1.12±1.27 vs. 3.75±2.79, P=0.031), and between AAH + AIS + MIA groups and IAC group (0.83±1.13 vs. 4.12±2.69, P<0.001). There were no statistically significant differences in other CT perfusion parameters of hemodynamics among different pathological subtypes of LUAD (P>0.05). The low-dose perfusion parameter IRF TO of revolution CT has the potential to be employed in the differential diagnosis of different pathological subtypes of LUAD.

Efficacy and Safety of HepaSphere Drug-Eluting Bead Transarterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy as the Second-Line Treatment in Advanced Hepatocellular Carcinoma.

Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) compared to HAIC in patients with advanced HCC. In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety. Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3-4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084). The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC.

Abstract C015: FGFR1 and RB1 genetic alteration impair clinical benefit of CDK4/6 inhibitors plus endocrine therapy in HR+/HER2- advanced breast cancer

Abstract Background: One of the great challenges for HR+/HER2- advanced breast cancer (ABC) is to determine who respond poorly to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). Chemotherapy is still used in HR+/HER2- patients. We aimed to explore cfDNA biomarkers for CDK4/6i plus endocrine therapy (ET), and compare its efficacy with chemotherapy in subgroups stratified by clinical and cfDNA characteristics. Method: Patients diagnosed with HR+/HER2- advanced breast cancer underwent first-line CDK4/6i plus ET or chemotherapy in Peking University Cancer Hospital from January 2018 to June 2022 were enrolled in this study. Baseline blood samples of patients were collected before first-line treatment for cfDNA sequencing. Results: Among all the 125 patients included in this study, the median PFS (mPFS) of CDK4/6i plus ET group (n=51) was significantly longer than patients treated with chemotherapy(n=74) (22.0 vs. 16.0 months, P = 0.025). In multivariate analysis, RB1 loss (Hazard ratio [HR] = 6.4, adjusted P = 0.031), FGFR1 gain (HR: 4.9, adjusted P = 0.030) were associated with shorter PFS of patients treated with CDK4/6i plus ET. A better efficacy of CDK4/6i plus ET was observed in patients with visceral metastasis, higher Ki-67 (≥20%) and smaller SLD (&amp;lt; 35mm) than chemotherapy. In subgroup analysis, interaction effects were found between RB1 loss (P interaction = 0.028), FGFR1 gain (P interaction = 0.004) and first-line treatment. Conclusion: This study revealed that FGFR1 gain and RB1 loss are independent prognostic factors for PFS of CDK4/6i plus ET, and chemotherapy was not superior to CDK4/6i plus ET in the absence of FGFR1 gain and RB1 loss, which might improve selection of patients for CDK4/6 inhibitors. Citation Format: Jianxin Zhong, Bin Shao, Hanfang Jiang, Huiping Li. FGFR1 and RB1 genetic alteration impair clinical benefit of CDK4/6 inhibitors plus endocrine therapy in HR+/HER2- advanced breast cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C015.

CT radiomics in the identification of preoperative understaging in patients with clinical stage T1-2N0 esophageal squamous cell carcinoma.

Predicting preoperative understaging in patients with clinical stage T1-2N0 (cT1-2N0) esophageal squamous cell carcinoma (ESCC) is critical to customizing patient treatment. Radiomics analysis can provide additional information that reflects potential biological heterogeneity based on computed tomography (CT) images. However, to the best of our knowledge, no studies have focused on identifying CT radiomics features to predict preoperative understaging in patients with cT1-2N0 ESCC. Thus, we sought to develop a CT-based radiomics model to predict preoperative understaging in patients with cT1-2N0 esophageal cancer, and to explore the value of the model in disease-free survival (DFS) prediction. A total of 196 patients who underwent radical surgery for cT1-2N0 ESCC were retrospectively recruited from two hospitals. Among the 196 patients, 134 from Peking University Cancer Hospital were included in the training cohort, and 62 from Henan Cancer Hospital were included in the external validation cohort. Radiomics features were extracted from patients' CT images. Least absolute shrinkage and selection operator (LASSO) regression was used for feature selection and model construction. A clinical model was also built based on clinical characteristics, and the tumor size [the length, thickness and the thickness-to-length ratio (TLR)] was evaluated on the CT images. A radiomics nomogram was established based on multivariate logistic regression. The diagnostic performance of the models in predicting preoperative understaging was assessed by the area under the receiver operating characteristic curve (AUC). Kaplan-Meier curves with the log-rank test were employed to analyze the correlation between the nomogram and DFS. Of the patients, 50.0% (67/134) and 51.6% (32/62) were understaged in the training and validation groups, respectively. The radiomics scores and the TLRs of the tumors were included in the nomogram. The AUCs of the nomogram for predicting preoperative understaging were 0.874 [95% confidence interval (CI): 0.815-0.933] in the training cohort and 0.812 (95% CI: 0.703-0.912) in the external validation cohort. The diagnostic performance of the nomogram was superior to that of the clinical model (P<0.05). The nomogram was an independent predictor of DFS in patients with cT1-2N0 ESCC. The proposed CT-based radiomics model could be used to predict preoperative understaging in patients with cT1-2N0 ESCC who have undergone radical surgery.

Abstract C035: Chemotherapy plus HER2-targeted therapy versus endocrine therapy plus HER2-targeted therapy as first-line treatment in patients with HR+/HER2+advanced breast cancer: A real-world trial

Abstract Purpose:This study is a real-world research to compare the efficacy of using chemotherapy plus anti-HER2 therapy versus endocrine therapy plus anti-HER2 therapy as first-line treatment for HR+/HER+ advanced breast cancer patients, aiming at providing a better treatment option for patients. Patients and methods: This study enrolled patients with advanced breast cancer who had complete medical records and were treated in the breast oncology department of Peking University Cancer Hospital from October 2010 to October 2022. These patients were pathologically confirmed with HR+/HER2+ and underwent first-line treatment with anti-HER2 therapy + endocrine therapy (HE group) or anti-HER2 therapy + chemotherapy (with/without endocrine maintenance therapy) (HC group). HER2 positive was defined as HER2+++ or HER2++ on immunohistochemical staining of tumor tissue and fluorescence in situ hybridization (FISH) testing showing HER2 gene amplification in patients. HR+ was considered when more than 1% of tumor cells expressed estrogen receptor (ER) and/or progesterone receptor (PR). The primary endpoints being investigated are progression-free survival (PFS) and overall survival (OS). The second endpoint is objective response rate (ORR) and clinical benefit rate (CBR). Results:From October 2010 to October 2022, a total of 181 patients who met the inclusion criteria were enrolled in the study. Among them, 18 patients received endocrine therapy + anti-HER2 therapy in the first-line treatment stage, while 163 patients received chemotherapy + anti-HER2 therapy (70 patients underwent endocrine maintenance therapy). The median follow-up time was 67 months. The median PFS (mPFS) of the patients in HC group and the HE group were 14.32 months (95% confidence interval (CI) 12.83-15.81) and 9.78 months (95%CI 4.48-15.8), respectively (p=0.299), and no significant statistical difference was observed. Similarly, no significant statistical difference was achieved in the median OS (mOS) of the HC group and the HE group patients, with 126.87 months (95%CI 102.08-151.658) versus 96.00 months (95%CI 78.41-113.59) (p=0.076). In the HC group, the mPFS of patients who received endocrine maintenance therapy and those who did not receive endocrine therapy were 16.24 months (95%CI 12.11-20.37) and 12.36 months (95%CI 10.26-14.46), respectively. The ORR of the two groups of patients were 46.6% and 16.7% (p=0.0015), respectively. Conclusion: The analysis demonstrated that the combination of anti-HER2 therapy with endocrine therapy is not inferior to the combination of anti-HER2 therapy with chemotherapy as first-line treatment for HR+/HER2+ advanced breast cancer. It provides compelling evidence to support the selection of endocrine therapy plus HER2-targeted therapy as a first-line treatment strategy that that enhances the quality of life for patients without shortening their survival time. Citation Format: Yuehua Liang, Hui Ping Li, Zehui Yun. Chemotherapy plus HER2-targeted therapy versus endocrine therapy plus HER2-targeted therapy as first-line treatment in patients with HR+/HER2+advanced breast cancer: A real-world trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C035.

Exploration of molecular markers related to chemotherapy efficacy of hepatoid adenocarcinoma of the stomach.

Preoperative neoadjuvant chemotherapy may not improve the prognosis of patients with hepatoid adenocarcinoma of the stomach (HAS), a rare pathological type of gastric cancer. Thus, the study aimed at the genomic and transcriptomic impacts of preoperative chemotherapy on HAS. Patients with HAS who underwent surgical resection at Peking University Cancer Hospital were retrospectively included in this study. Whole exome sequencing and transcriptome sequencing were performed on pre-chemotherapy, non-chemotherapy and post-chemotherapy samples. We then compared the alterations in molecular markers between the post-chemotherapy and non-chemotherapy groups, and between the chemotherapy-effective and chemotherapy-ineffective groups, respectively. A total of 79 tumor samples from 72 patients were collected. Compared to the non-chemotherapy group, the mutation frequencies of several genes were changed after chemotherapy, including TP53. In addition, there was a significant increase in the frequency of frameshift mutations and cytosine transversion to adenine (C > A), appearance of COSMIC signature 6 and 14, and a reduced gene copy number amplification. Interestingly, the same phenomenon was observed in chemotherapy-ineffective patients. In addition, many HAS patients had ERBB2, FGFR2, MET and HGF gene amplification. Moreover, the expression of immune-related genes, especially those related to lymphocyte activation, was down-regulated after chemotherapy. Chemotherapy is closely associated with changes in the molecular characteristics of HAS. After chemotherapy, at genomic and transcriptome level, many features were altered. These changes may be molecular markers of poor chemotherapeutic efficacy and play an important role in chemoresistance in HAS. In addition, ERBB2, FGFR2, MET and HGF gene amplification may be potential therapeutic targets for HAS.

Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in locally advanced gastroesophageal junction and gastric carcinoma.

Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status. 376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis. We observed significant survival differences among the four groups (p < 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0, and TRG0-1N+ were not reached, whereas these of patients with TRG2-3N+ were 17.37 months (95% CI, 14.14-20.60 months) and 39.97 months (95% CI, 27.05-52.89 months). TRG combined with ypN status was still an independent predictor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. Chi-squared test showed TRG combined with ypN status was significantly associated with different preoperative treatments (p < 0.001). Patients receiving immunotherapy achieved the highest TRG0N0 rate (31.9%). Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate.