5097 Background: The current standard of care (SoC) for metastatic hormone-sensitive prostate cancer (mHSPC) is androgen deprivation + systemic therapy. Oligometastatic HSPC, however, represents a unique disease entity following the STAMPEDE trial, where de novo mHSPC patients with a CHAARTED-defined low disease burden (DN-mHSPC-LV) had a hazard ratio of death of 0.68 after prostate radiotherapy (PRT). Despite the SABR-COMET results of a survival benefit with stereotactic RT on metachronous oligometastatic sites of predominantly prostate patients, radical RT (RRT) in the DN-mHSPC-LV setting has not been studied. This study analysed the outcomes of such patients receiving RRT to all disease sites vs PRT alone. Methods: DN-mHSPC-LV patients receiving RRT to the prostate and all oligometastatic sites (Arm A) vs PRT alone (Arm B) in a Hong Kong tertiary hospital between 1 st January 2012 and 1 st January 2023 were reviewed. Outcomes of progression-free survival (PFS), overall survival (OS) and treatment-related toxicity (TrT) were analysed using the Kaplan-Meier and multivariable Cox-proportional hazards models. Results: 127 eligible patients (60 in Arm A & 67 in Arm B) were identified. The median numbers of oligometastatic sites of 1-3 and = > 4 were balanced between the two arms. The median Gleason score was 8 in both arms. Median T/N/M staging was mostly balanced but more patients in Arm B had N1 disease. Presenting PSA (ng/mL) was higher in Arm A (38.5) than Arm B (27.9). Arm A received up to 76Gy/38# to the prostate + a boost of up to 67.5Gy or stereotactic RT to the oligometastatic sites. Arm B received 55-60Gy/20# to the prostate alone. Patients were started on long-term androgen deprivation therapy. Median follow-up was 40.2 months and 30.3 months in Arms A and B, respectively. Median PFS was not reached (NR) in either of the treatment arms. On multivariate analysis, 5-year PFS was 86.1% vs 50.3% in Arms A and B, respectively ( P = 0.0173; HR 0.213; 95% CI 0.059-0.761). OS data were not yet mature and there was no difference in TrT between the arms. Conclusions: To our knowledge, this is the first study comparing radical RT against the SoC of prostate RT alone in DN-mHSPC-LV. Radical RT was well tolerated and is significantly cheaper than next-generation hormone agents in prostate cancer. 5-year PFS was significantly better with radical RT vs prostate RT alone. PFS is an established surrogate for OS in prostate cancer. This study therefore justifies prospective studies on RRT for DN-mHSPC-LV. More importantly, as prospective trials with an OS endpoint in prostate cancer will take close to a decade to mature, this study provides interim evidence to support radical treatment in this group of patients, in whom cure or long-term control may be achieved, where prospective trials are anticipated to take much longer to complete.

PURPOSE:Stereotactic body radiation therapy (SBRT) to the prostate and pelvis in high-risk prostate cancer (HR-PC) may shorten treatment, but acute toxicity and quality of life (QoL) outcomes compared with conventional fractionated intensity modulated radiation therapy (IMRT) remain uncertain. We report acute toxicity and early QoL outcomes from a randomized phase 2 trial. METHODS AND MATERIALS:Between 2019 and 2024, 121 patients with node-negative HR-PC were randomized to SBRT (40 Gy in 5 weekly fractions to prostate, 36.25 Gy to seminal vesicles, and 25 Gy to pelvis) or IMRT (76 Gy in 38 daily fractions: 50 Gy to prostate and pelvis, followed by 26 Gy prostate boost), with androgen deprivation therapy (18-24 months). The primary endpoint was acute grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity occurring during radiation therapy or within 120 days after treatment completion (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0). Secondary endpoints included patient-reported outcomes (Expanded Prostate Cancer Index Composite, International Prostate Symptom Score). RESULTS:Baseline characteristics were balanced (median age, 72 years; 49.6% prostate-specific antigen ≥20 ng/mL; 69% Gleason ≥8). Acute grade ≥2 GI toxicity occurred in 8.3% with SBRT versus 39.0% with IMRT (P <.0001); grade ≥2 GU toxicity in 23.3% versus 36.1%, respectively (P =.126). Grade 3 diarrhea occurred in 1 patient with IMRT; no grade ≥3 GU events were observed. At 1 month, bowel QoL declined more with IMRT (-10.4) than SBRT (-1.9; P =.0008), as did urinary domain decline (-11.3 vs -7.5). At 1 week, the International Prostate Symptom Score and QoL worsened less with SBRT than with IMRT (+4.55 vs +7.49; P =.062; QoL P =.029). CONCLUSIONS:Once-weekly SBRT to the prostate and pelvis significantly reduced acute GI toxicity and provided comparable GU safety relative to IMRT, with supportive early patient-reported outcomes. These findings extend SBRT evidence to the pelvis-inclusive setting in HR-PC and support phase 3 trials.

Abstract Background Acral lentiginous melanoma (ALM) is the predominant melanoma subtype in East Asian populations, accounting for roughly 50–58% of cases, compared with 2–3% in populations of European ancestry. ALM is genomically and biologically distinct from sun-exposed cutaneous melanoma, and East Asian and acral patients were markedly under-represented in the pivotal anti–PD-1 registration trials. At the time this study was designed, no prospective trial had evaluated a checkpoint inhibitor specifically in ALM. We conducted a phase II trial to estimate the activity of pembrolizumab in this population. Methods In this single-centre, single-arm, open-label phase II trial, adults with metastatic or locoregionally advanced inoperable ALM who were naïve to anti–PD-1/PD-L1 therapy received pembrolizumab 200 mg intravenously every 3 weeks until progression, unacceptable toxicity, or withdrawal. The primary endpoint was objective response rate (ORR) by RECIST 1.1. Secondary endpoints included duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety (CTCAE v4.0). A Simon minimax two-stage design (P0=0.10, P1=0.30, α=0.05, power=80%) planned enrolment of up to 28 patients. Results Between February 2017 and June 2019, 9 patients were enrolled before recruitment was halted for slow accrual, the interval availability of reimbursed pembrolizumab, and a low observed response signal. Median age was 72 years (range 48–78); 6 (67%) were male; all had ECOG performance status 0 and metastatic disease; 7 (78%) had received prior therapy. One patient achieved a partial response (ORR 11.1%, 95% CI 0.0–31.6%), with a DoR of 19 months; 3 had stable disease and 4 progressed. CBR (response or stable disease ≥12 weeks) was 44.4% (95% CI 12.0–76.9). At a median follow-up of 7.6 months, median PFS was 3.4 months (95% CI 1.4–21.3) and median OS was 7.6 months (95% CI 2.0– 34.3). Two grade 3 adverse events occurred, both assessed as unrelated to study drug; no treatment-related grade ≥3 events were recorded. In an exploratory analysis, an LDH-to–upper-limit-of-normal ratio >1.5 was associated with worse OS (median 4.3 vs 26.5 months; HR 4.58, 95% CI 0.82–25.7; log-rank p=0.06). Conclusions Recruitment was constrained by disease rarity and a shifting reimbursement landscape, and the trial closed before completing stage I. Within these limitations, single-agent pembrolizumab showed only modest activity in advanced ALM, consistent with the limited efficacy subsequently reported in larger contemporary acral melanoma cohorts. The exploratory association between elevated LDH ratio and poorer survival warrants prospective evaluation. What is already known / what this study adds ALM is the commonest melanoma subtype in East Asia but was almost absent from the trials that established PD-1 blockade; no prospective checkpoint-inhibitor trial in pure ALM existed when this study was designed. In this prospective phase II trial, single-agent pembrolizumab produced an ORR of 11.1% with modest survival, consistent with limited activity later reported in larger acral cohorts. An exploratory signal linking elevated LDH ratio to poorer survival supports its prognostic relevance and the need for collaborative, biomarker-driven trials dedicated to ALM.

6052 Background: Methylthioadenosine phosphorylase (MTAP) loss has been associated with poor outcomes in various cancers, including nasopharyngeal carcinoma (NPC). Homozygous deletion of the MTAP locus is one of the most frequent somatic changes in NPC, creating opportunities for therapeutic targeting. However, the concordance between MTAP IHC and FISH for detecting MTAP loss, and the prognostic impact of partial MTAP loss, has not been fully explored. This study evaluated the prevalence of MTAP loss, correlation between IHC and FISH, and association of MTAP expression with time to progression (TTP), progression-free survival (PFS) and overall survival (OS). Methods: MTAP expression was analyzed by IHC, and locus loss was confirmed using FISH in tumors M0 (non-metastatic) NPC patients. Correlations between MTAP IHC and FISH results were analyzed to assess concordance, sensitivity, and specificity. Kaplan-Meier survival curves and log-rank tests compared survival distributions, while Cox proportional hazards models were applied for univariate and multivariate analyses. Subgroup analyses were performed by tumor, nodal and overall stage (AJCC 8th edition). Results: Among 175 patients, 65 (36.0%) exhibited IHC 0 and FISH-negative MTAP loss. Concordance rate between IHC 0 and FISH-negative was 94.9%. MTAP loss was significantly correlated with higher N2–3 and stage III–IVA disease (Pearson correlation coefficients: 0.81 and 0.73, respectively; p < 0.0001). Based on receiver operating curve (ROC) analysis, the optimal MTAP cutoff for progression was 110. Partial MTAP loss (MTAP 0–109) was significantly associated with shorter TTP compared to MTAP 110–300 (median TTP: 4.6 years vs. 15.8 years; p = 0.04). In multivariate analysis, MTAP <110 remained significant for TTP (HR = 0.65; CI 0.48-0.98 p = 0.04) after adjusting for grouped N stage. Subgroup analyses demonstrated that MTAP <110 was significantly associated with shorter PFS in N2–3 patients (HR 0.5 CI 0.28-0.9 p = 0.02) and shorter TTP in stage III–IVA patients (HR 0.61 CI 0.37-1.0 p = 0.05). Conclusions: Partial MTAP loss (IHC <110) is associated with worse outcomes in NPC, particularly shorter TTP and PFS, with significant prognostic value in advanced nodal and overall stage disease. High concordance between IHC and FISH supports IHC as a reliable diagnostic tool. These findings highlight MTAP expression as a potential prognostic biomarker for NPC, warranting further validation and exploration of targeted therapies.

Background Central nervous system (CNS) metastases are common among patients with epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC). Osimertinib in combination with chemotherapy beyond osimertinib progression may minimize CNS progression. Method In this retrospective analysis, patients with advanced EGFR mutation positive NSCLC and brain metastases who received platinum-based chemotherapy (PbChT) after disease progression on osimertinib were enrolled. The primary endpoint was real-world CNS progression-free survival (rwCNS-PFS) between patients who received PbChT with and without osimertinib continuation. Secondary endpoints included competing risk analysis of CNS progression and incidence of salvage radiotherapy to brain. Results A total of 101 patients were analyzed, out of which, 39 (39%) continued osimertinib with chemotherapy (OSI+ cohort) and 62 (61%) received chemotherapy alone (OSI- cohort). Median rwCNS-PFS was significantly longer in the OSI+ cohort (9.0 months, 95% CI 6.6-11.4) than the OSI- cohort (5.7 months, 95% CI 4.6-6.9) (HR 0.37, 95% CI 0.18-0.76, p=0.007). This remained significant after adjustment for EGFR mutation, line of osimertinib treatment, prior radiotherapy to brain, and CNS progression on osimertinib monotherapy. Estimated probability of CNS progression at 6 months was 5.6% in OSI+ cohort versus 20.9% in OSI- cohort. Incidence of salvage radiotherapy to brain was lower in the OSI+ cohort (15%) compared to OSI- cohort (24%). Conclusion In patients with EGFR mutation positive NSCLC and brain metastases, continuing osimertinib with chemotherapy after progression on osimertinib significantly reduced risk of CNS progression. Prospective studies are warranted to define the optimal treatment strategy for this patient population. Microabstract This retrospective study analyzed the risk of central nervous system (CNS) progression of patients with advanced EGFR mutation positive NSCLC and brain metastases who received platinum-based chemotherapy after disease progression on osimertinib. Real world CNS progression-free survival was significantly reduced in patients who continued osimertinib with chemotherapy compared to those who received chemotherapy alone (HR 0.37, p=0.007), which remained significant after multivariate analysis. Incidence of salvage radiotherapy was also lower in patients who continued osimertinib with chemotherapy. In patients with EGFR mutation positive NSCLC and brain metastases, continuing osimertinib beyond progression with chemotherapy reduces risk of CNS progression.

Background:JAK/STAT interferon signaling interacts with the PI3K/AKT/mTOR pathway to drive hepatocellular carcinoma (HCC) progression and metastasis. RSAD2, an interferon-inducible gene, is upregulated by the PI3K/AKT/mTOR pathway and serves as a key factor for metabolic reprogramming to promote stem-like properties of cancer stem cells and tumor proliferation. In patients with resected HCC, RSAD2 upregulation showed an association with microvascular invasion, which is a proven risk factor for developing HCC metastasis. This clinical observation was compatible with preclinical findings. On the other hand, RSAD2 upregulation has been reported to confer poor prognosis in breast and gastric cancers. However, further clinical study of RSAD2 in HCC is lacking. As a result, we investigated the clinical implications of RSAD2 gene expression in HCC patients, in terms of its associations with survival, the presence of extra-hepatic metastasis, and other clinical manifestations. Methods: We studied 309 treatment-naïve HCC patients, as well as data from the TCGA and GTEx databases. Results:RSAD2 gene expression was differentially upregulated in HCC tumors when compared to normal liver tissues (p < 0.01). Elevated RSAD2 mRNA levels in the blood and the presence of extra-hepatic metastasis were independent prognostic factors for poor overall survival (OS) (p < 0.01). The median OS of patients with high RSAD2 expression vs. low expression were 5.4 vs. 14.2 months, respectively (p < 0.01). A high RSAD2 mRNA level was significantly correlated with the presence of extra-hepatic metastasis, nutritional disturbance, and functional impairment after controlling for confounding clinical factors (p < 0.05). Conclusions: High RSAD2 gene expression is associated with poorer OS, the presence of extra-hepatic metastasis, and quality-of-life disturbances in HCC patients.

Background Despite transarterial chemoembolization (TACE) serving as the first-line treatment for patients with intermediate stage B hepatocellular carcinoma (HCC), complete response rates are generally below 27%. Purpose To compare the efficacy and safety of an anhydrous cisplatin suspension in ethiodized oil-based TACE versus a conventional aqueous cisplatin emulsion in the treatment of participants with HCC. Materials and Methods In this prospective, multicenter, randomized controlled trial conducted from September 2016 to February 2023, participants from three hospitals in Hong Kong were randomized to an experimental or control group in a 1:1 ratio. The experimental group received an anhydrous cisplatin suspension (4 mL of ethiodized oil with 20 mg of cisplatin powder). The control group received a conventional aqueous cisplatin emulsion. TACE was performed within 4 weeks after randomization in two to three treatments, 2 months apart. Response was assessed with CT and digital subtraction angiography during subsequent TACE. Primary end points were complete tumor response and severe adverse events. Secondary end points included progression-free survival and overall survival (OS). Survival outcomes were compared using the log-rank test and hazard ratios with 95% CIs. Results A total of 77 participants were included (median age, 68 years; IQR, 64-75 years; 59 men). At 6 months, the complete tumor response rate was higher in the suspension group (90% [35 of 39 participants]) compared with the emulsion group (47% [18 of 38 participants]; P < .001). Serious adverse events were similar in the suspension group (2.3% [three of 128 procedures]) and emulsion group (5.2% [eight of 153 procedures]; P = .21). Median progression-free survival was higher in the suspension group (21.1 months; 95% CI:14.3, 38.9) compared with the emulsion group (10.4 months; 95% CI: 7.3, 13.4) (hazard ratio, 0.35; P < .001). Median OS was higher in the suspension group (53.3 months; 95% CI: 40.5, not reached) than in the emulsion group (36.0 months; 95% CI: 25.7, 46.6) (hazard ratio, 0.32; P = .004). Conclusion Ethiodized oil-based TACE using an anhydrous cisplatin suspension resulted in better complete tumor response, progression-free survival, and OS rates compared with the conventional aqueous cisplatin emulsion. ClinicalTrials.gov identifier NCT03268499 © RSNA, 2025 Supplemental material is available for this article.

BackgroundAn increasing number of immuno-therapeutic agents have proven efficacy in hepatocellular carcinoma (HCC). Inflammatory markers (c-reactive protein, interleukin-8 and inflammatory score) have been found to be prognostic factors in HCC patients. These inflammatory markers have demonstrated correlations with quality of life (QOL) disturbances in fatigue, appetite loss and nutritional concern. Type I interferon response triggered by HCC could be responsible for an inflammatory state and anorexia-cachexia syndrome leading to these specific QOL impairment. Peripheral blood Interferon Stimulated Gene 15 (ISG15) messenger ribonucleic acid (mRNA) transcript level, a biomarker for type I interferon response, was evaluated for its prognostic significance for overall survival (OS) in a prospective cohort of HCC patients. QOL measurement was employed to systemically capture and quantify patients’ clinical manifestations for correlations with ISG15 mRNA transcript level.MethodsClinical, QOL and laboratory data of 340 treatment naïve HCC patients were collected at study entry. ISG15 mRNA transcript levels in circulating leucocytes were quantified. Independent prognostic factors for OS were identified. Correlation analyses between ISG15 mRNA transcript level and scores of QOL factors were performed.ResultsHigh ISG15 mRNA transcript level in circulating leucocytes was an independent prognostic factor for poor OS (hazard ratio 1.62 [1.23-2.15]; p-value<0.01). The median OS of patients with high ISG15 gene expression was significantly shorter than those with low expression, 4.7 versus 14.3 months respectively (p-value<0.03). There were significant correlations between high ISG15 mRNA transcript level and worse scores in QLQ-C30 fatigue, appetite loss and QLQ-HCC18 nutritional disturbances (p-values <0.05).ConclusionsElevated ISG15 mRNA transcript level in peripheral blood leucocytes was an independent poor prognostic factor for OS in HCC patients. Patients with higher ISG15 gene expression, suggesting more intense type I interferon response, had significantly worse OS. High ISG15 gene expression demonstrated significant correlations with QOL disturbances in fatigue, appetite loss and nutritional concern. These QOL factors could be capturing the anorexia-cachexia manifestations from interferon response induced by HCC.

BACKGROUND & AIMS:Recurrence in patients with hepatocellular carcinoma (HCC) treated with curative surgery or ablation follows a bimodal pattern, with early recurrence peaking at 6 months to 1 year, and late recurrence peaking at 3 to 4 years. We postulate that the use of antiviral therapy may reduce late recurrence by improving control of chronic inflammation. METHODS:Patients with positive HBsAg and HCC (HBV-related HCC) who received curative surgery or ablation from October 2000 to July 2017 were recruited from Prince of Wales Hospital in Hong Kong. The primary endpoint was recurrence-free survival (RFS). We conducted time-dependent survival analysis and 6-month and 12-month landmark analyses to evaluate the impact of antiviral therapy on overall recurrence and late recurrence, respectively. We also conducted a secular trend analysis by stratifying patients into an early cohort (2001-2005) and a late cohort (2011-2015), representing periods of low and high antiviral usage, respectively, to assess changes in recurrence hazard over time. RESULTS:A total of 765 patients with HBV-related HCC were recruited. Median RFS was 31.1 (95% CI 26.6-39.4) months for the entire cohort. In the time-dependent survival analysis, antiviral therapy was associated with improved RFS in the univariate model (hazard ratio [HR] 0.84, 95% CI 0.74-0.99, p = 0.042), with a similar trend observed in the multivariable model (HR 0.86, 95% CI 0.72-1.03, p = 0.106). Baseline antiviral therapy significantly improved RFS in both the 6-month (HR 0.75, 95% CI 0.59-0.96, p = 0.019) and 12-month (HR 0.62, 95% CI 0.47-0.82, p = 0.001) multivariable landmark analyses. Secular trend analysis revealed attenuation of the second recurrence peak in the cohort with higher antiviral exposure. CONCLUSION:Among patients with HBV-related HCC who underwent curative surgery or ablation, antiviral therapy was associated with a reduction in late recurrence. IMPACT AND IMPLICATIONS:The classical bimodal recurrence pattern of hepatocellular carcinoma following curative treatment was established prior to the widespread use of effective antiviral therapy. It is unclear whether this recurrence pattern is still valid in the era of effective antiviral therapy. The current study shows that antiviral therapy can reduce late recurrence, resulting in loss of the second peak of the classical bimodal recurrence pattern. This study provides further evidence highlighting the importance of adherence to antiviral therapy in patients who received curative treatment for hepatocellular carcinoma.

Epidermal growth factor receptor (EGFR)-driven non-small cell lung cancer (eLC) is a leading cause of death. The FLAURA study showed that upfront osimertinib (U-OSI) led to better overall survival (OS) than gefitinib or erlotinib, regardless of T790M status in advanced disease. However, if sequenced optimally, sequential OSI (S-OSI) in T790M-positive patients after first- or second-generation EGFR-tyrosine kinase inhibitors (F-S-EGFR-TKI) should theoretically lead to better OS than U-OSI. To identify the best sequencing strategy in this group of patients. A multicentre retrospective study was conducted on treatment-naive eLC patients who had received an F-S- EGFR-TKI between 1 January 2016 and 31 December 2020 in three tertiary NHS hospitals in the UK. Compliance to national recommendation of T790M testing was analysed. Survival outcomes of T790M testing and S-OSI were estimated with the Kaplan–Meier and Cox Proportional Hazard models. In 84/122 evaluable patients, after F-S-EGFR-TKI, only 50

Abstract Background Cancer patients often consider CINV as one of the most disturbing side effects of cytotoxic chemotherapy. Adriamycin and cyclophosphamide (AC), considered by many to be part of the standard adjuvant regimen for breast cancer patients, is highly emetogenic. Despite adopting optimal antiemetic prophylaxis, the control of CINV remains modest for some patients. Among Chinese breast cancer patients receiving adjuvant AC chemotherapy, the present analysis aims to determine the association of the number of risk factors for CINV with (i) likelihood of antiemetic treatment failure; (ii) time to first vomiting in 1st AC cycle. Methods: We retrieved data from three previously reported prospective antiemetic studies on patients who received AC, in whom different antiemetic regimens were administered. Treatment failure was defined as (i) not achieving CR (CR= no vomiting and no use of rescue medication over 120 hours after start of AC), or (ii) experiencing nausea (nausea VAS >/= 5mm during the 120 hours). Multivariate logistic regression models were applied to identify potential factors associated with the development of CINV. The Cochran–Armitage trend test was utilized to assess possible trends in the relationship between treatment failure and number of identified risk factors. The time-to-treatment failure curves, as classified by the number of identified factors in each subgroup, were evaluated using the Kaplan–Meier method. Results: Based on multivariate analysis of 303 breast cancer patients, not achieving CR was more likely among non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, history of motion sickness and history of vomiting in pregnancy. Experience of nausea was more likely in non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, and history of motion sickness. Treatment failure in terms of ‘no CR’ was associated with increased number of risk factors that an individual patient displayed; the figures increased from 18.8% for those with 0 risk factor to 94.1% for those with 4 risk factors (p < 0.0001). Treatment failure in terms of nausea was associated also with increased number of risk factors; the figures increased from 25.9% for those with 0 risk factor to 83.3% for patients with 3 risk factors (p < 0.0001). Time to first vomiting was significantly related to number of identified factors (p < 0.0001). Among patients who had 0, 1, 2 and 3 risk factors, the 24-hour rate of ‘no vomiting’ were 81.3%, 80.3%, 66.7%, 53.7% and 17.7%, respectively; similar trends were observed for analyses on 48-hour and 72-hour rates. Conclusions: The present study confirmed that reported risk factors for CINV in the literature were important in Chinese breast cancer patients receiving AC chemotherapy. Furthermore, patients who had more risk factors had increased likelihood of treatment failure and shorter time to first vomiting. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research Citation Format: Winnie Yeo, Nicole Ngai, Horatio Yeo, Dong Lai, Elizabeth Pang, Carol Kwok, Thomas Lau, Frankie Mo. Factors associated with treatment failure for chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving adjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-12.

Background and AimsThere has been a lack of prospective data on treatment after immune checkpoint inhibitor (ICI) in hepatocellular carcinoma (HCC). We conducted a phase II multicentred study on cabozantinib in HCC after ICI treatment.MethodsThis is an investigator-initiated single-arm clinical trial involving academic centres in Hong Kong and Korea. Key eligibility criteria include diagnosis of HCC; refractoriness to prior ICI-based treatment; Child-Pugh A liver function. Maximally two prior lines of therapy were allowed. All patients were commenced cabozantinib at 60mg/day. The primary endpoint was progression-free survival (PFS).ResultsTotal 47 patients were recruited from Oct 2020 to May 2022. The median follow-up was 11.2 months. In the study, 27 and 20 patients received one and two prior therapies. The median PFS was 4.1 months (95%CI:3.3-5.3). The median OS was 9.9 months (95%CI:7.3-14.4), and the 1-year OS rate was 45.3%. Partial response and stable disease occurred in 3 (6.4%) and 36 (76.6%) of patients. When used as a second-line treatment (n=20), cabozantinib was associated with a median PFS and OS of 4.3 (95%CI:3.3-6.7) and 14.3 months (95%CI:8.9-NR). The corresponding median PFS and OS was 4.3 (95%CI:3.3-11.0) and 14.3 months (95%CI:9.0-NR) for those receiving ICI-based regimen with proven benefits (n=17). Commonest grade 3-4 TRAE was thrombocytopenia (6.4%). The median dose of cabozantinib was 40mg/day. The number of prior therapy was an independent prognosticator (one vs. two; HR=0.37; p=0.03).ConclusionsCabozantinib demonstrates efficacy in patients with prior ICI. The survival data of second-line cabozantinib following the first-line ICI regimen provide reference for clinical trial testing post-ICI therapy. The number of prior line of treatment may be considered a stratification factor in randomized study.Impact and ImplicationsThere is a lack of prospective data on systemic therapy following prior immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC). The current phase II clinical trial reported the efficacy and safety data of cabozantinib in patients with prior ICI-based treatment. Exploratory analyses showed that the performance of cabozantinib differed significantly when used as second or third-line treatment. The above data could be used a reference for clinical practice and design of future clinical trials on subsequent treatment following ICIs.Trial registrationClinicalTrials.gov Identifier: NCT04588051.

BACKGROUND:Treatment response evaluated by tumour size change is an important indicator for outcome prediction. Advanced nasopharyngeal carcinoma (adNPC) grows irregularly, and so the unidimensional measurement may not be accurately applied to adNPC for outcome prediction. This study aimed to evaluate values of unidimensional and volumetric measurements for treatment response to induction chemotherapy (IC) for outcome prediction in adNPC and compared the values with that of RECIST 1.1 guideline. MATERIALS AND METHODS:Pre-treatment and post-IC magnetic resonance images (MRIs) from 124 patients with stage III-IVA NPC were retrospectively reviewed. Sums of the maximum unidimensional diameters (D) and volumes of the targeted tumours (primary tumour and two largest metastatic lymph nodes) on the pre- (Dpre and Vpre) and post-IC MRIs (Dpost-IC and Vpost-IC) and percentage changes in D (Δ D%) and V (ΔV%) between two scans were calculated and correlated with disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS) using Cox regression analysis. Area under the curves (AUCs) of independent measurements and RECIST groups (RECIST response and non-response groups) for predicting disease recurrence, locoregional recurrence, and distant metastases, respectively, were calculated and compared using the DeLong test. RESULTS:Univariable analysis showed correlations between high Dpost-IC with poor DFS and DMFS (P < 0.05), but not with LRRFS (P = 0.07); high Vpost-IC and low ΔV% (less decrease in volume on post-IC) with poor DFS, LRRFS, and DMFS (P < 0.05); and no correlations between Dpre, ΔD%, and Vpre and the outcomes (P > 0.05). Multivariable analysis showed that ΔV% was the only independent measurement for outcomes (P < 0.05). Compared with RECIST groups, ΔV% of 47.9% (median value) showed a higher AUC for disease recurrence (0.682 versus 0.526, P < 0.01) and for locoregional recurrence (0.782 versus 0.585, P < 0.01), but not for distant metastases (0.593 versus 0.518, P = 0.26). CONCLUSIONS:Volumetric measurement to evaluate treatment response to IC outperformed unidimensional measurement and RECIST guideline in outcome prediction in adNPC.

Purpose Extranodal extension (ENE) has the potential to add value to the current nodal staging system (N8th) for predicting outcome in nasopharyngeal carcinoma (NPC). This study aimed to incorporate ENE, as well as cervical nodal necrosis (CNN) to the current stage N3 and evaluated their impact on outcome prediction. The findings were validated on an external cohort. Methods & Materials Pre-treatment MRI of 750 patients from the internal cohort were retrospectively reviewed. Predictive values of six modified nodal staging systems that incorporated four patterns of ENE and two patterns of CNN to the current stage N3 for disease-free survival (DFS) were compared with that of N8th using multivariate cox-regression and concordance statistics in the internal cohort. Performance of stage N3 for predicting disease recurrence was calculated. An external cohort of 179 patients was used to validate the findings. Results Incorporation of advanced ENE, which infiltrates into adjacent muscle/skin/salivary glands outperformed the other five modifications for predicting outcomes (p < 0.01) and achieved a significantly higher c-index for 5-year DFS (0.69 vs 0.72) (p < 0.01) when compared with that of N8th staging system. By adding advanced ENE to the current N3 increased the sensitivity for predicting disease recurrence from 22.4 % to 47.1 %. The finding was validated in the external cohort (5-year DFS 0.65 vs. 0.72, p < 0.01; sensitivity of stage N3 increased from 14.0 % to 41.9 % for disease recurrence). Conclusion Results from two centre cohorts confirmed that the radiological advanced ENE should be considered as a criterion for stage N3 disease in NPC.