Resistance to anti-PD1-based immune checkpoint blockade (ICB) remains a problem for the treatment of metastatic melanoma. Tumor cells as well as host myeloid cells can express the immune checkpoint ligand CD155 to regulate immune cell function. However, the effect of tumor CD155 on the immune context of human melanoma has not been well described. This observational study characterizes tumor CD155 ligand expression by metastatic melanoma tumors and correlates results with differences in immune cell features and response to ICB.Experimental Design: Pretreatment tumor specimens, from 155 patients with metastatic melanoma treated with ICB and from 50 patients treated with BRAF/MEK-directed targeted therapy, were assessed for CD155 expression by IHC. Intratumor T-cell features were analyzed using multiplex-immunohistofluorescence for CD8, PD1, and SOX10. Correlations were made between CD155 tumor level and bulk tumor RNA sequencing results, as well as clinical RECIST response and progression-free survival.Results: High pretreatment CD155 tumor levels correlated with high parenchymal PD1 þ CD8 þ /CD8 þ T-cell ratios (PD1 tR ) and poor response to anti-PD1 therapy. In PDL1 negative tumors, high CD155 tumor expression was associated with patients who had poor response to combination anti-PD1/ CTLA4 therapy.Conclusions: Our findings are the first to suggest that tumor CD155 supports an increase in the fraction of PD1 þ CD8 þ T cells in anti-PD1 refractory melanoma tumors and, further, that targeting the CD155 pathway might improve response to anti-PD1 therapy for patients with metastatic melanoma.

Background:International guidelines, including NICE, recommend using the 21-gene Recurrence Score assay for guiding adjuvant treatment decisions in ER+, HER2-negative early breast cancer (BC). We investigated the impact of adding this assay to standard pathological tests on clinicians'/patients' treatment decisions and on patients' decisional conflict in the United Kingdom.Methods:In this prospective multicentre study, eligibility criteria included: ER+ HER2-negative BC (N0/Nmic for patients ⩽50 years; ⩽3 positive lymph nodes for patients >50 years) and being fit for chemotherapy. Physicians'/patients' treatment choices and patients' decisional conflict were recorded pre- and post testing.Results:The analysis included 137 patients. Overall, adjuvant treatment recommendations changed in 40.7% of patients, with the direction of the change consistent with the Recurrence Score results (net decrease in chemotherapy recommendation rate in low Recurrence Score patients and net increase in high Recurrence Score patients). Patients' choices were generally consistent with physicians' recommendations. Post-testing, patients' decisional conflict decreased significantly (P<0.0001). In the 67 patients meeting the NICE criteria for testing, the recommendation change rate was 49.3%.Conclusions:Recurrence Score testing significantly influenced treatment recommendations overall and in the subgroup of patients meeting the NICE criteria, suggesting that this test could substantially alter treatment patterns in the United Kingdom.

Background: Peptide receptor radionuclide therapy (PRRT) is an approved treatment modality for gastroenteropancreatic neuroendocrine tumours (GEP NETs), Although Phase III randomised clinical trial data is not available for NETs of other site of origin, in practice, PRRT is used more widely in clinical practice, based on its mechanism of targeting the somatostatin receptor. Use of PRRT for lung (bronchial) NET, specifically typical and atypical carcinoid (TC, AC), has been reported only in small retrospective case series. This multicentre study adds to the evidence regarding utility of PRRT for lung NETs. Materials and Methods: A retrospective chart review of patients with TC and AC who received 177 Lu-dotatate PRRT between January 2002 and June 2019 in six hospitals across Australia was undertaken. Data regarding demographics, efficacy and toxicity was evaluated at each site by the treating clinician. Results: Forty-eight patients (32 AC, 15 TC, 1 unclassified) received a median of four 177 Lu-dotatate treatments. There was a median of one prior line of systemic treatment (range: 0-3). The response rate to 177 Lu-dotatate was 33%, with a median overall survival of 49 months (range of 3-91), at a median follow up of 33 months. This compares favourably with GEP NET. Overall toxicity was recorded as modest. Conclusions: 177 Lu-dotatate PRRT in patients with lung NETs is used in real world practice, where it appears well-tolerated with some efficacy. Further evidence could be obtained through a global prospective clinical or registry trial.

Aim Colorectal cancer (CRC) is the third most common cancer in Australia, and survival after diagnosis of metastatic disease is improving. Our aim was to assess trends in epidemiology, treatment, molecular testing and survival in patients with metastatic CRC (mCRC). Methods Clinical data from February 2013 to December 2018 was recorded in a prospective, observational, multicenter cohort study conducted in Queensland, Australia, examining clinical and molecular biomarkers in cases of mCRC. Results A total of 159 patients who had metastasis diagnosed after February 2013 were included in survival analysis. Median age at diagnosis was 63.9 years, but 29% had early‐onset disease (diagnosis aged <50 years). Median overall survival was 2.5 years (95% confidence interval [CI], 2.2–3.0) for the 159 patients included in survival analysis. Independent factors correlated with poor prognosis included right‐sided primary tumor, neutrophil–lymphocyte ratio >5, increased alkaline phosphatase level (ALP) and an increasing number of sites of metastatic disease. In contrast, metastasectomy was associated with improved overall survival (adjusted HR = 0.29’ 95% CI, 0.16–0.54), with similar survival between patients who had liver and non‐liver metastasectomy sites. Half (10/20) of the BRAF mutant CRC were also microsatellite unstable. The proportion of detected mutations amongst tested samples increased over time for Kirsten Rat Sarcoma (KRAS; OR [per year] = 1.19; 95% CI, 1.01–1.39). Concurrently, the methods of molecular genetics testing employed in routine clinical practice changed towards the adoption of next‐generation sequencing. Conclusions Metastasectomy in mCRC may be beneficial regardless of the anatomical site of metastasis. The adoption of next‐generation sequencing techniques for molecular genetics testing coincided with a slightly increased rate of detection of KRAS and BRAF mutations, potentially reflecting greater test sensitivity. Further translational research is required in mCRC to define novel targets for treatment.

PURPOSE: International guidelines advocate for active surveillance as the preferred treatment strategy for patients with stage 1 testicular cancer after orchidectomy although a personalized discussion is required. MATERIALS AND METHODS: We conducted an analysis of individuals registered in iTestis, Australia's testicular cancer registry, to describe the patterns of relapse and outcomes of patients treated in Australia where the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Surveillance Recommendations are widely adopted. RESULTS: A total of 650 individuals diagnosed between 2000 and 2020 were included, 63% (411 of 650) seminoma and 37% (239 of 650) nonseminoma. The median age was 34 years (range 14-74). 26% (106 of 411) with seminoma and 15% (36 of 239) nonseminoma received adjuvant chemotherapy. After a median follow-up of 43 months (range 0-267) postorchidectomy, relapse occurred in 10% (43 of 411) of seminoma and 18% (43 of 239) of nonseminoma. The two-year relapse-free survival was 92% (95% CI, 89 to 95) and 82% (95% CI, 78 to 87) in seminoma and nonseminoma, respectively. All relapses (86 of 86) were detected at a routine surveillance visit; 98% (85 of 86) were asymptomatic and detected solely through imaging (62 of 86, 72%), tumor markers (6 of 86, 7%), or a combination (17 of 86, 20%). The most common relapse site was isolated retroperitoneal lymphadenopathy (53 of 86, 62%). No nonpulmonary visceral metastases occurred. At relapse, 98% (84 of 86) had International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis; 2 of 86 intermediate prognosis (both nonseminoma). No deaths occurred. CONCLUSION: In our cohort of stage 1 testicular cancer, where national surveillance recommendations have been widely adopted, recurrences were detected at routine surveillance visits and, almost exclusively, asymptomatic with IGCCCG good-prognosis disease. This provides reassurance that active surveillance is safe.

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