Primary Tumor Location Research Articles

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial

In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1. In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration-ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration-and adjusted mean change from baseline in patient-reported outcomes. Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI -0·71 to 3·16) in the durvalumab group and 0·35 (-1·63 to 2·32) in the placebo group. The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer. AstraZeneca.

What Is the Impact of Multimodal Treatment in Patients with Leiomyosarcoma of Bone? A Multicenter Study of 35 Patients with an Ultra-Rare Tumor Entity.

Primary leiomyosarcoma of bone (LMSoB) is extremely rare, comprising only <0.7% of primary malignant bone tumors, and is therefore considered an ultra-rare tumor entity. There is currently no consensus as to whether therapeutic strategies should be based on the biological characteristics of soft tissue leiomyosarcoma or on primary tumor localization in the bone. The use of perioperative chemotherapy and its effectiveness in this rare tumor entity remains unclear. We aimed to evaluate the impact of different treatment approaches in a multicenter setting with a total of 35 patients included. The 5-year overall survival (OS) was 74%. Patients with localized disease undergoing surgery had a significantly higher 5-year OS compared to patients who did not undergo surgical treatment (82% vs. 0%, p = 0.0015). Axial tumor localization was associated with worse event-free survival (EFS) probability (p < 0.001) and OS (p = 0.0082). A high proportion of our patients developed secondary metastases. Furthermore, the perioperative chemotherapy protocols applied to our patients were not associated with an improved EFS or OS. Therefore, the benefit of perioperative chemotherapy in LMSoB needs to be further investigated, and the choice of agents still needs to be clarified.

A Glimpse into the Role and Effectiveness of Splenectomy for Isolated Metachronous Spleen Metastasis of Colorectal Cancer Origin: Long-Term Survivals Can Be Achieved.

Background: Many papers exploring the role of resectioning metastases in colorectal cancer (CRC) have focused mainly on liver and lung sites, showing improved survival compared with non-resectional therapies. However, data about exceptional metastatic sites such as splenic metastases (SMs) are scarce. This paper aims to assess the role and effectiveness of splenectomy in the case of isolated metachronous SM of CRC origin. Methods: The patients' data were extracted after a comprehensive literature search through public databases for articles reporting patients with splenectomies for isolated metachronous SM of CRC origin. Potential predictors of survival were explored, along with demographic, diagnostic, pathology, and treatment data for each patient. Results: A total of 83 patients with splenectomies for isolated metachronous SM of CRC origin were identified. The primary CRC was at an advanced stage (Duke's C-70.3%) and on the left colon (45.5%) for most patients, while the median interval between CRC resection and SM was 24 months. The median overall survival after splenectomy was 84 months, and patients younger than 62 years presented statistically significantly worse overall survival rates than those ≥62 years old (p = 0.011). There was no significant impact on the long-term outcomes for factors including primary tumor location or adjuvant chemotherapy (p values ≥ 0.070, ns). Laparoscopic splenectomy was increasingly used in the last 20 years from 2002 (33.3% vs. 0%, p < 0.001). Conclusions: Splenectomy is the optimal treatment for patients with isolated metachronous SM of CRC, with the laparoscopic approach being increasingly used and having the potential to become a standard of care. Encouraging long-term survival rates were reported in the context of a multidisciplinary approach. Younger ages are associated with worse survival. Perioperative chemotherapy in the context of a patient diagnosed with SM of CRC origin appears to be a reasonable option, although the present study failed to show any significant impact on long-term survival.

The role of cytoreductive surgery and HIPEC for the treatment of primary and secondary peritoneal malignancies-experience from a tertiary care center in Germany.

Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69years. Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.

Abstract CT226: Phase 2 study of oral CCR4 antagonist FLX475 (tivumecirnon) plus pembrolizumab in subjects with head and neck squamous cell carcinoma (HNSCC) previously treated with checkpoint inhibitor

Abstract BACKGROUND: FLX475 (tivumecirnon) is a selective CCR4 antagonist designed to block the recruitment of immunosuppressive regulatory T cells (Treg) into the tumor microenvironment. The FLX475-02 trial (NCT03674567) is a phase 1/2 study of FLX475 as monotherapy and in combination with pembrolizumab in subjects with advanced cancer. Early encouraging data on the biologic effects, safety and antitumor activity of FLX475 have previously been presented. We now present the results from the Phase 2 cohort of combination therapy in subjects with head and neck squamous cell carcinoma (HNSCC) previously treated with checkpoint inhibitor (CPI-experienced). METHODS: Subjects with CPI-experienced, recurrent or metastatic (R/M) HNSCC received FLX475 100 mg orally once daily with pembrolizumab (200 mg IV Q3 weeks). The primary study objectives were safety and tolerability, and antitumor activity. The primary efficacy endpoint was objective response rate (ORR), based on RECIST 1.1 criteria. Additional efficacy endpoints included progression-free survival (PFS). Safety was evaluated as per CTCAE v4.03. Data cutoff was 11DEC2023. RESULTS: For the 32 subjects with HNSCC evaluable for response, median follow-up was 14.8 months (range 2.2-40.1) and median lines of prior therapy were 3 (1-6). Median age of subjects was 59 yrs; 94% were male and 75% were Caucasian. Primary tumor location was oropharynx in 56%. As previously reported, the only adverse event clearly determined to be treatment related to FLX475 to date has been asymptomatic and reversible QT prolongation (managed by dose reduction). Among the subjects evaluable for response regardless of HPV or PD-L1 status (n=32), confirmed partial response (cPR) was observed in 5 subjects (ORR: 15.6%, 95% CI 6-32%). Among the subgroup of subjects whose tumors were HPV positive (n=18), 8 (44%) experienced reduction from baseline in target lesion measurements and cPR was observed in 4 (ORR: 22.2%, 95% CI 9-46%). Among the subgroup of subjects whose tumors expressed PD-L1 (combined positive score [CPS] ≥1%) (n=22), cPR was observed in 4 (ORR: 18.2%, 95% CI 7-39%). At data cutoff, the HPV-positive subgroup median PFS was 2.9 months (95% CI 2-10.3) and 3 subjects were still on treatment. CONCLUSIONS: FLX475, an oral CCR4 antagonist, has previously demonstrated clear monotherapy activity in EBV+ extranodal NK/T-cell lymphoma and promising combination activity with pembrolizumab in EBV+ gastric cancer and CPI-naïve non-small cell lung cancer. In this completed Phase 2 cohort of subjects with CPI-experienced R/M HNSCC, FLX475 in combination with pembrolizumab was shown to be well tolerated and has demonstrated encouraging clinical activity particularly in those with HPV-positive tumors, supporting the continued development of this combination therapy for CPI-experienced HNSCC. Citation Format: Jameel Muzaffar, Kedar Kirtane, Rebecca Redman, Muh-Hwa Yang, Tae Min Kim, Stephen Liu, Ryan Lynch, Julie Brahmer, Patricia LoRusso, Brian Henick, Sung-bae Kim, Yin-Hsun Feng, Michael Chisamore, Paul Kassner, Dirk Brockstedt, Nicole Nasrah, Rakesh Goyal, William Y. Ho, Victoria Villaflor. Phase 2 study of oral CCR4 antagonist FLX475 (tivumecirnon) plus pembrolizumab in subjects with head and neck squamous cell carcinoma (HNSCC) previously treated with checkpoint inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT226.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Salvage Therapy of Relapsed/Refractory Germ Cell Tumors: A Single-Center Experience

Introduction: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. Methods: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1–3 plus etoposide 750 mg/m2 on days 1–3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. Results: The median age of the patients was 31 (range 18–62). The median follow-up was 31.1 months (95% CI, 28.9–33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1–43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. Conclusion: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.

Development of a prediction model for recurrence in patients with colorectal peritoneal metastases undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

IntroductionCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes for selected patients with colorectal peritoneal metastases (PM), but recurrence rates are high. The aim of this study was to develop a tool to predict recurrence in patients with colorectal PM that undergo CRS-HIPEC. Materials and methodsFor this retrospective cohort study, data of patients that underwent CRS-HIPEC for colorectal PM from four Dutch HIPEC centers were used. Exclusion criteria were perioperative systemic therapy and peritoneal cancer index (PCI) ≥20. Nine previously identified factors were considered as predictors: gender, age, primary tumor characteristics (location, nodal stage, differentiation, and mutation status), synchronous liver metastases, preoperative Carcino-Embryonal Antigen (CEA), and peritoneal cancer index (PCI). The prediction model was developed using multivariable Cox regression and validated internally using bootstrapping. The performance of the model was evaluated by discrimination and calibration. ResultsIn total, 408 patients were included. During the follow-up, recurrence of disease occurred in 318 patients (78%). Significant predictors of recurrence were PCI (HR 1.075, 95% CI 1.044–1.108) and primary tumor location (left sided HR 0.719, 95% CI 0.550–0.939). The prediction model for recurrence showed fair discrimination with a C-index of 0.64 (95% CI 0.62, 0.66) after internal validation. The model was well-calibrated with good agreement between the predicted and observed probabilities. ConclusionWe developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC.

Intraoperative magnetic resonance imaging in glioma surgery: a single-center experience.

To investigate the effect of intraoperative magnetic resonance imaging (Io MRI) on overall and progression-free survival (OS and PFS), on the extent of resection (EOR) in patients with glioma, and impact of the radiological diagnosis on the decision to continue the surgery when a residual mass was detected on Io MRI. The study comprised 153 glioma patients who received surgical treatment between 2013 and 2023. One-hundred twenty-five of them had Io MRI guidance during surgery. The remainder 28 patients constituted the control group who did not undergo Io MRI. All patients' age at surgery, gender, initial radiological diagnosis, primary tumor localization, EOR, last histopathological diagnosis, and the follow-up periods were recorded. The rate of tumor recurrence in Io MRI cases was significantly lower compared to the cases in the control group (p < .0001). It was decided to continue the operation in 45 Io MRI applied cases. This raised the gross total resection (GTR) rate from 33.6% to 49.6% in the Io MRI group. The frequency of GTR was significantly higher in patients with an initial radiological diagnosis of low grade glioma than those with high grade glioma. The shortest OS was seen in occipital gliomas. In this study, the convenience provided by the high-field MRI device was explored and proven both in reducing the tumor burden, increasing the PFS, and providing the surgeon with a maximal resection in the first operation.

Increased risk of multiple metastases and worse overall survival of metastatic pancreatic body and tail cancer: a retrospective cohort study.

Pancreatic cancer (PC) is a lethal disease, especially metastatic PC. And it can be divided into two types: head pancreatic cancer (H-PC) and body and tail pancreatic cancer (BT-PC). Prior studies have proved that they have different overall survival (OS) and should be regarded as two different categories of PC. At present, there remains a gap in the field regarding OS across different primary tumor locations and metastatic sites, as well as the metastatic patterns associated with various primary tumor locations in patients with metastatic PC. Thus, our study aims to address this gap by analyzing data from a large population sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The different prognosis of different primary tumor locations and metastatic sites may indicate that different primary locations and metastatic sites may require different therapy and follow-up strategy. It is hoped that these findings will lay the groundwork for future guideline updates and related research. Patients with pathologically confirmed stage IV metastatic PC from the National Cancer Institute's SEER program between 2010 and 2015 were included, excluding patients with various tumors, without specifying age, specific sites of metastasis, or OS. Data including age, race, gender, tumor size, T stage, N stage, grade, sites, number of metastatic sites, surgery, radiotherapy, chemotherapy and years of diagnoses were collected from the SEER database. OS was defined as the period from initial diagnosis to the date of death. Specific metastatic sites for the different primary locations of tumor were compared. Survival was analyzed by Cox regression analyses. Overall, 14,406 patients with metastatic PC were included in this research (7,104 of H-PC and 7,302 of BT-PC). Gender proportion, tumor size, T stage, N stage, number of metastatic sites surgery of the primary lesions and radiotherapy were different between BT-PC and H-PC. The proportion of only 1 metastatic site was 68.3% in H-PC compared with 58.3% in the BT-PC. The BT-PC was an independent risk factor for liver metastases compared with the H-PC [odds ratio (OR) =1.510; 95% confidence interval (CI): 1.320-1.727]. No matter for those with multiple metastases, or for those with solitary liver or lung metastases, patients with metastatic H-PC showed better OS (P<0.001, P=0.001, P=0.04, respectively). In patients with solitary liver metastases, worse OS was observed in the BT-PC than the H-PC [hazard ratio (HR) =1.109; 95% CI: 1.046-1.175]. The metastatic BT-PC had worse OS and increased risk to suffer from liver and multiple metastases. Moreover, in patients with solitary metastases, those with liver metastases presented poorest survival.

THE EFFECT OF PRIMARY LOCALIZATION OF COLORECTAL CANCER&#x0D; ON KRAS STATUS AND ITS PROGNOSTIC VALUE

Relevance: Colorectal cancer (CRC), arising from the right-sided or left-sided colon, is a separate clinical and pathological unit. The status&#x0D; of KRAS and its predictive value in CRC remain controversial.&#x0D; The study aimed to explore the effect of primary tumor localization on KRAS gene status in CRC.&#x0D; Methods: The study included 60 patients with colon and rectal cancer. The KRAS mutation test was performed on paraffin-coated tumor samples&#x0D; using PCR methods. Colon cancer was divided into right-sided colon cancer (RSCC) and left-sided colon cancer (LSCC).&#x0D; Results: KRAS mutation was found much more often in rectal cancer (RC) and sigmoid colon (SC) (p=0.413) than in tumors in other parts&#x0D; of the colon. A combined analysis of our data and previously published data showed that KRAS mutation was more common in PSTC, especially&#x0D; in the area of the hepatic bend of the colon than in LSTC (p=0.120). The association of the KRAS mutation with the patient’s age (p&lt;0.012) and&#x0D; the duration of hospitalization (p&lt;0.001) was established.&#x0D; Conclusion: Our study revealed no significant difference in the KRAS status between colon cancer and rectal cancer. However, KRAS&#x0D; mutation was much more common in RSCC compared to LSCC. Patients with RSCC with mutated KRAS also had a worse prognosis and&#x0D; required longer hospitalization compared to wild-type KRAS. However, patients with LSCC did not demonstrate a similar effect.

The Profile of Sinonasal Tumors with Orbital Involvement in Dr. M. Djamil General Hospital, Padang, Indonesia: A 10-Year Overview

Background: Sinonasal tumors are rare tumors, either malignant or benign, that vary greatly based on the origin and primary tumor location in the sinonasal tract. The close anatomical relationship between the sinonasal tract and the orbital cavity makes orbital involvement very common (50%-80%) in sinonasal tumors, and this indicates a negative prognostic factor in sinonasal malignancy. The purpose of this study is to demonstrate the profile of sinonasal tumors with orbital involvement in our center.&#x0D; Methods: Retrospective study from oncology subdivision files and medical records from January 2011 – December 2020. Collected data including age, gender, the clinical manifestations of orbital involvement, primary location, histopathology, and management of sinonasal tumors.&#x0D; Results: There were 35 patients examined by the oncology subdivision either directly came or consulted from the ENT department, consisting of 18 (51.4%) males and 17 (48.6%) females. The age of patients ranged from 11 to 83 years old. with the most common age groups being 41-50 and 51-60 (25.7% in each age group). The majority of the patients (77.1%) had presented with proptosis. Maxillary sinus was the most common (45.7%) primary site of tumors, and squamous cell carcinoma was the most common (51.4%) histopathology found. Most of the patients (37.1%) were treated with a combination of chemotherapy and radiotherapy.&#x0D; Conclusion: Orbital involvement commonly occurs in malignant sinonasal tumors with proptosis as a major clinical presentation. A combination of chemotherapy and radiotherapy was the most common practice management because the tumors were unresectable at the time of presentation.

Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P=0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P=0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P=0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P=0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P<0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P<0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P=0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P<0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P=0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P=0.164). In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

Development and validation of a novel model to predict recurrence-free survival and melanoma-specific survival after sentinel lymph node biopsy in patients with melanoma: an international, retrospective, multicentre analysis

The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage. Patients older than 13 years with confirmed primary melanoma who underwent sentinel lymph node biopsy (SLNB) between Oct 29, 1997, and Nov 11, 2013, at four European melanoma centres (based in Berlin, Germany; Amsterdam and Rotterdam, the Netherlands; and Warsaw, Poland) were included in the development cohort. Potential predictors of recurrence-free and melanoma-specific survival assessed were sex, age, presence of ulceration, primary tumour location, histological subtype, Breslow thickness, sentinel node status, number of sentinel nodes removed, maximum diameter of the largest sentinel node metastasis, and Dewar classification. A prognostic model and nomogram were developed to predict 5-year recurrence-free survival on a continuous scale in patients with stage pT1b or higher melanomas. This model was also calibrated to predict melanoma-specific survival. Model performance was assessed by discrimination (area under the time-dependent receiver operating characteristics curve [AUC]) and calibration. External validation was done in a cohort of patients with primary melanomas who underwent SLNB between Jan 30, 1997, and Dec 12, 2013, at the Melanoma Institute Australia (Sydney, NSW, Australia). The development cohort consisted of 4071 patients, of whom 2075 (51%) were female and 1996 (49%) were male. 889 (22%) had sentinel node-positive disease and 3182 (78%) had sentinel node-negative disease. The validation cohort comprised 4822 patients, of whom 1965 (41%) were female and 2857 (59%) were male. 891 (18%) had sentinel node-positive disease and 3931 (82%) had sentinel node-negative disease. Median follow-up was 4·8 years (IQR 2·3-7·8) in the development cohort and 5·0 years (2·2-8·9) in the validation cohort. In the development cohort, 5-year recurrence-free survival was 73·5% (95% CI 72·0-75·1) and 5-year melanoma-specific survival was 86·5% (85·3-87·8). In the validation cohort, the corresponding estimates were 66·1% (64·6-67·7) and 83·3% (82·0-84·6), respectively. The final model contained six prognostic factors: sentinel node status, Breslow thickness, presence of ulceration, age at SLNB, primary tumour location, and maximum diameter of the largest sentinel node metastasis. In the development cohort, for the model's prediction of recurrence-free survival, the AUC was 0·80 (95% CI 0·78-0·81); for prediction of melanoma-specific survival, the AUC was 0·81 (0·79-0·84). External validation showed good calibration for both outcomes, with AUCs of 0·73 (0·71-0·75) and 0·76 (0·74-0·78), respectively. Our prediction model and nomogram accurately predicted patient-specific risk probabilities for 5-year recurrence-free and melanoma-specific survival. These tools could have important implications for clinical decision making when considering adjuvant treatments in patients with high-risk melanomas. Erasmus Medical Centre Cancer Institute.

A prediction model for lung metastases in patients with indeterminate pulmonary nodules in newly diagnosed colorectal cancer

IntroductionMultidisciplinary teams treating patients with newly diagnosed Colorectal Cancer (CRC) often encounter the appearance of Indeterminate Pulmonary Nodules (IPNs) that warrants follow–up with repetitive medical imaging and anxiety for patients. We determined the incidence of IPNs in patients with newly diagnosed CRC and developed and validated a model for individualized risk prediction of IPNs being lung metastases. Material and methodsNewly diagnosed CRC who underwent surgery between November 2011 to June 2014 were included to create the risk model, developed using both clinical experience and statistical selection. Discrimination and calibration slopes of the risk score were evaluated in an independent temporal validation sample. A nomogram is presented to assist clinicians in estimating an individual risk score. ResultsOut of 2111 CRC patients staged with chest CT, 204 (9.6%) had IPNs and 54/204 (26%) had lung metastases. We identified 4 predictors: “location of primary tumour”, “pathological nodal stage”, “size of the largest nodule” and “extrapulmonary synchronous metastases at diagnosis”. Discrimination of the final model in the validation sample was demonstrated by the difference in mean predicted risk between progressed cases en non-progressed cases (49% versus 21%, p = <0.001). ConclusionA prediction model with 4 clinical risk factors can be used to assist multidisciplinary teams in the prediction of individualized risk of lung metastases and imaging strategy in patients with IPNs and newly diagnosed colorectal cancer. The model performed well in new patients not included in the model development.

Clinicopathologic comparison of basal cell carcinoma among a diverse patient population in Los Angeles County.

Basal cell carcinoma (BCC) is the most common malignancy in the United States. The majority of cases are identified in Non-Hispanic Whites (NHW) and are far less demonstrated in patients of colour (POC). However, the Hispanic population represents a large and growing proportion of the US population, and skin cancer diagnoses in Hispanics are rising. Thus, the goal of this study is to examine clinicopathologic differences between BCC in Hispanics versus NHW. A retrospective chart review of Hispanic and NHW patients with BCC at Los Angeles County+USC Medical Center from January 2018 to March 2020 was performed. In total, 101 BCC samples from the first 100 patients identified of Hispanic ancestry, as well as 50 BCC samples identified from the first 50 patients identifying as NHW, were included for analysis. Patient characteristics (age, sex, medical history, and ethnicity), as well as tumour characteristics (location, subtype, tumour depth, and perineural invasion), were collected. We used between subjects t-tests for continuous variables, and chi-square tests for categorical variables. In total, 151 specimens were collected amongst 122 subjects (79 Hispanics and 43 NHW patients). Among NHW, the majority of patients (74.4%) were men, but among the Hispanic population, the majority (68.4%) were female (p<0.001). Prior history of other skin cancer was more common among NHW (67.4%) than Hispanics (31.6%) (p=<0.001). The Hispanic population had a significantly higher proportion of head and neck tumours (p=0.0004) but a lower proportion of extremity tumours (p=0.001) compared to NHW. Pigmented BCC was significantly more common among Hispanic patients (p<0.01). Finally, within the Hispanic group, there was a significant association between sex and histology (p=0.004), with Hispanic men demonstrating more aggressive mix histology compared to Hispanic women. Our study supports the notion that BCC disparities occur among POC compared to NHW. This includes variations in epidemiologic factors such as sex and past medical history, primary tumour location, and pathologic characteristics. Further research should be conducted to identify additional differences in skin cancer presentation in POC to reduce the gaps in skin cancer knowledge and care.

Abstract 6400: Tislelizumab combined with XELOX as a neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinomas: A prospective, phase II trial

Abstract Background: Combing anti-PD-(L)1 antibody with chemotherapy in neoadjuvant therapy of gastric/gastroesophageal junction (G/GEJ) adenocarcinomas is a promising strategy, but clinical data are remain insufficient. Whether immunotherapy biomarkers in previous studies (TMB, MSI, PD-L1, etc.) have equivalent predictive value for G/GEJ remains to be verified. In this phase II clinical trial of tislelizumab in combination with chemotherapy, potential therapy-related biomarkers in tumor samples, and changes in the tumor microenvironment during treatment were analyzed, and a predictive model for efficacy was developed. Methods: This was a prospective, single-center, single-arm, phase II trial. Patients with G/GEJ adenocarcinomas (stage cT3-4aN+M0) were treated with PD-1 inhibitor tislelizumab in combination with oxaliplatin plus capecitabine (XELOX) as neoadjuvant treatment for 2 or 3 cycles. The primary endpoint was the major pathological response (MPR). The secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, and safety. Tumor samples underwent RNA-sequencing (Amoy Diagnostics Co Ltd, Xiamen, China), to identify potential biomarkers, and a predictive model was developed to explore factors influencing tumor response and survival. Results: 28 patients were enrolled; mean age was 59.5 years (SD = 8.2), 19 (67.9%) patients were male; 14 (50.0%) patients with primary tumor location in the stomach, and 14 (50.0%) patients with primary tumor location in the GEJ. All patients were EB virus negative. Except one patient with PMS2 loss, 27 patients were pMMR. Nine (32.1%) patients achieved MPR after treatment, with four (14.3%) of them achieved pCR. The R0 resection rate was 96.4%, with 14 (50.0%) patients achieved objective response. No serious adverse events were reported. The most common grade 2 TRAEs during neoadjuvant treatment were anemia (5 of 28, 17.86%) and nausea (3 of 28, 10.71%). Analysis of differentially expressed genes revealed enrichment of the antigen processing and presentation pathway in the MPR group, while the TGF-β signaling pathway was enriched in the non-MPR group. Notably, the differential immune microenvironment analysis also uncovered significant differences in the TGF-β signature between the MPR and non-MPR groups. Additionally, a therapeutic response prediction model (HT score) was developed with an AUC of 0.98 (0.932-1) in the training set, and its performance was validated in publicly available datasets. Conclusion: Tislelizumab combined with XELOX holds promise as a neoadjuvant therapy for resectable G/GEJ adenocarcinomas, especially for EBV- and pMMR population, offering a well-tolerated safety profile. Moreover, the HT score has the potential to predict treatment efficacy in this regimen. Trial registration numbers: NCT05507658 and NCT05508399. Citation Format: Haikun Zhou, Tao Han, Lei Tuo, Qingchuan Yang, Ruiqi Gao, Pengfei Yu, Jiangpeng Wei, Changbin Zhu, Jin Wang, Peng Cheng, Xiang Kang, Sihui Pi, Hui Liu, Xiaoxi Pan, Xiaohua Li, Gang Ji. Tislelizumab combined with XELOX as a neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinomas: A prospective, phase II trial [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 6400.

Abstract 4979: Genomic profiling of early-onset metastatic colorectal cancer based on tumor sample location

Abstract Background: Here, we describe analyses towards identifying and comparing genetic variations between the primary and metastatic sites in early-onset metastatic colorectal cancer patients. Methods: We selected patients with early-onset metastatic colorectal cancer (under 50 years old) using data from the American Association for Cancer Research Project GENIE (version 14.1). We used the Fisher exact test to compare genetic mutations between the primary tumor and metastatic sites, complemented by the Benjamini-Hochberg adjustment method. Results: In a total of 1,791 patients with early-onset metastatic colorectal cancer, 27.1% had tumor samples from metastatic sites, while the majority, 72.9%, were from the primary tumor location. The most common mutations found were in the TP53 gene (77.6%), followed by APC (76.0%), KRAS (42.4%), and PIK3CA (19.0%). Notably, the metastatic samples had a significantly higher occurrence of SMAD4 mutations compared to their primary site counterparts (20.8% vs. 14.0%, p&amp;lt;0.001, q&amp;lt;0.001). Conversely, the primary tumor samples exhibited higher frequencies of TCF7L2 and ARID1A mutations (16.9% vs. 10.6%, p&amp;lt;0.001, q&amp;lt;0.001, and 13.0% vs. 6.4%, p&amp;lt;0.001, q&amp;lt;0.001, respectively). Conclusion: Determining the specific genes responsible for the formation of metastatic tumors is crucial for a deeper understanding of the disease's underlying biology in early-onset metastatic colorectal cancer. Such genomic details are crucial to pave the way to the discovery of potential biomarkers for diagnosis and the development of new cancer therapeutics. Citation Format: Muhammet Ozer, Suleyman Y. Goksu, Busra Bacik Goksu, Nina N. Sanford, Amy Jones, Nilesh Verma, Syed Kazmi. Genomic profiling of early-onset metastatic colorectal cancer based on tumor sample location [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 4979.

Abstract 3779: Genomic and clinical characterization of metastatic patterns using real-word data from a large cohort of colorectal cancer patients

Abstract Background: Colorectal cancers (CRCs) can exhibit disparate metastatic patterns that affect outcomes. We investigated associations between genomic features and organ-specific metastatic tropism and we compared the frequency of actionable alterations detected in patients undergoing longitudinal clinical sequencing. Methods: We analyzed data for 6574 tumors from 6153 CRC patients, including 4510 primary and 2064 metastatic specimens. All patients had microsatellite stable (MSS) disease and were treated at Memorial Sloan Kettering. Paired primary and metastatic samples were available for 203 patients. Tumors were sequenced with MSK-IMPACT, a targeted DNA sequencing assay that identifies genomic alterations in 341-505 genes. Clinical annotations included sex, stage at diagnosis (Dx), and primary tumor location. History of metastatic disease was automatically retrieved from radiology reports using validated natural language processing methods; time to specific-site metastasis was modeled with Cox regression. False discovery rate (FDR) was used to correct for multiple hypothesis testing. The OncoKB knowledge base was used to identify clinically actionable alterations. Results: Liver (n=1068, 51.7%), peritoneal (n=269, 13.0%) and lung metastases (n=263, 12.7%) accounted for the majority of non-primary sequenced specimens. The frequency of actionable alterations (OncoKB Level≥3A) did not vary between unmatched metastatic and primary samples (12.3% vs 11.4%, p=0.302). In primary tumor samples from patients with localized disease at the time of diagnosis, TGFB pathway alterations were associated with increased risk of metastasis to the brain (HR=2.41, p=0.028), bone (HR=2.10, p&amp;lt;0.001), peritoneum (HR=1.82, p=0.001) and liver (HR=1.42, p=0.049). Alterations in the RAS pathway were associated with increased risk of lung (HR=1.47, p=0.009), peritoneum (HR=1.54, p=0.021) and liver (HR=1.44, p=0.026) metastases. By contrast, WNT pathway alterations were associated with a lower risk of developing lung (HR=0.69, p=0.033) and peritoneal metastasis (HR=0.68, p=0.081). Among patients with paired primary and metastatic samples, no significant difference was observed between the frequency of clinically actionable alterations in primary vs. metastatic specimens (16.7% vs. 18.2%, p=0.794). Presence of metastases-private or primary-private alterations did not correlate with site-specific metastasis risk. Conclusions: The risk of developing metastatic disease and organ-specific dissemination might be linked to genomic abnormalities detectable at the localized stage. No significant difference in the frequency of actionable alterations was observed between primary and metastatic CRC samples. Citation Format: Paolo Manca, Ayush V. Kris, Henry Walch, Christopher Fong, Justin Jee, Karl Pichotta, Nikolaus Schultz, Walid K. Chatila, Rona Yaeger, Francisco Sanchez-Vega. Genomic and clinical characterization of metastatic patterns using real-word data from a large cohort of colorectal cancer patients [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 3779.

Abstract 925: Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection

Abstract Introduction: Anti-EGFR monoclonal antibody plus doublet chemotherapy is the mainstay of first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Some of these patients might undergo secondary resection. However, there is no standardized suggestion on whether colorectal cancer liver metastasis patients should keep target therapy after secondary resection. NCCN guidelines suggest chemotherapy only in patients receiving primary liver resection. Whether we could spare the use of target therapy after secondary resection is the main aim of our study. Methods: Using Taiwan's National Health Insurance Research Database, we established a cohort of KRAS wild-type mCRC patients treated with first-line anti-EGFR therapy plus doublet chemotherapy between 2013 and 2018. Secondary surgery was defined as either resection of liver metastases or radiofrequency ablation. Results: 5694 stage IV mCRC patients received anti-EGFR MAb plus doublet chemotherapy as a first-line treatment between 2013 and 2018. 174 patients were enrolled in the final analysis, with 153 continuing anti-EGFR MAb after secondary resection and 21 patients without anti-EGFR MAb. Compared with those who without anti-EGFR therapy after secondary resection, patients who continued anti-EGFR MAb exhibited significantly longer overall survival (OS; median, 43.8 vs. 31.9 months, p = 0.031) but not in time to treatment failure (TTF; median, 22.2 vs. 26.6 months, p = 0.841). The OS benefits of continuing anti-EGFR MAb remained regardless of left-sided or right-sided primary tumors (40.9 vs. 43.0 months, p = 0.980). The patient cohort from 2016 to 2018 showed more prolonged survival than from 2012 to 2015 (not reached vs. 40.450, p = 0.0305). TTF has no statistical difference when considering patient cohort or primary tumor location. In multivariate analyses, continuing first-line anti-EGFR MAb therapy after secondary resection remained an independent predictor of longer OS. Conclusion: For mCRC patients who received secondary resection after first-line anti-EGFR and doublet chemotherapy, continuing anti-EGFR MAb after resection was associated with significantly longer OS regardless of primary tumor sidedness. Citation Format: Yao-Yu Hsieh, Chin-Wen Tsai, T-CARE Group, Yi-Hsieh Liang. Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection [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 925.

Abstract 4976: The impact of obesity on survival in epithelial gynecological tumors

Abstract Background: The impact of obesity on the survival of patients with epithelial gynecological tumors is not yet clear. We aim to elucidate the impact of body mass index (BMI) on epithelial gynecological tumors in a large tertiary center at Saudi Arabia. Methods: We retrospectively reviewed the medical files of all patients with pathologically confirmed epithelial gynecological tumors at our center. Then, we assessed the difference in overall survival (OS) according to primary tumor location, BMI, stage at presentation, and performance status (PS) at presentation using log-rank tests. Results: 400 patients were included in the analysis. The mean age at diagnosis was 56.1±13 years. 242 (60.5%) patients were diagnosed with uterine carcinomas, 137 (34.3%) with ovarian carcinomas, and 21 (5.3%) with cervical carcinomas. 278 (69.5%) patients were obese at presentation, 74 (18.5%) were overweight, 43 (10.8%) were within normal range, and 7 (1.8%) were underweight. The PS at presentation was 0, 1, 2, 3, and 4 in 351 (87.8%), 17 (4.3%), 10 (2.5%), 16 (4%), and 6 (1.5%) patients, respectively. Cervical cancer was associated with long OS, while ovarian cancers demonstrated poor prognosis (p=0.0159). There was no difference in OS between different BMI groups (p=0.072). Patients with stage 4 cancers had significantly shorter OS (p&amp;lt;0.0001). Patients with PS 4 at presentation was associated with the worst prognosis (p&amp;lt;0.0001). Interpretation: Shorter OS was associated with ovarian carcinomas, advanced staging, and poor PS at presentation. BMI classification had no impact on OS. Further studies are needed to confirm our findings. Citation Format: Ahmed Badran, Mahmoud Elshenawy, Waleed Fallatah, Abdullaah K. Hinkston, Saad S. Ali, Mohammed Ali Omar, Abdulaziz M. Alaklabi, Hytham M. Abdalla, Tarek Z. Arabi, Belal N. Sabbah, Hamed Alhusaini. The impact of obesity on survival in epithelial gynecological tumors [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 4976.