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Background: Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions., Methods: We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed., Results: We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy., Conclusions: This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect., Trial Registration Number: ACTRN12613000198729., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The clinical success of immune-checkpoint inhibitors (ICI) in both resected and metastatic melanoma has confirmed the validity of therapeutic strategies that boost the immune system to counteract cancer. However, half of patients with metastatic disease treated with even the most aggressive regimen do not derive durable clinical benefit. Thus, there is a critical need for predictive biomarkers that can identify individuals who are unlikely to benefit with high accuracy so that these patients may be spared the toxicity of treatment without the likely benefit of response. Ideally, such an assay would have a fast turnaround time and minimal invasiveness. Here, we utilize a novel platform that combines mass spectrometry with an artificial intelligence-based data processing engine to interrogate the blood glycoproteome in melanoma patients before receiving ICI therapy. We identify 143 biomarkers that demonstrate a difference in expression between the patients who died within six months of starting ICI treatment and those who remained progression-free for three years. We then develop a glycoproteomic classifier that predicts benefit of immunotherapy (HR=2.7; p=0.026) and achieves a significant separation of patients in an independent cohort (HR=5.6; p=0.027). To understand how circulating glycoproteins may affect efficacy of treatment, we analyze the differences in glycosylation structure and discover a fucosylation signature in patients with shorter overall survival (OS). We then develop a fucosylation-based model that effectively stratifies patients (HR=3.5; p=0.0066). Together, our data demonstrate the utility of plasma glycoproteomics for biomarker discovery and prediction of ICI benefit in patients with metastatic melanoma and suggest that protein fucosylation may be a determinant of anti-tumor immunity., Competing Interests: CP, PA, GX, AM, RR, XC, DS, KL and FS are or were employees of InterVenn Biosciences, a company that identifies biomarkers and commercializes diagnostic tests. YN consults for Pfizer, Novartis, Merck, BMS, and InterVenn Biosciences Non CE Honoraria: Pfizer, Immunocore. JM has industry funding to Moffitt Cancer Center unrelated to this manuscript from Morphogenesis, Jackson Laboratories, Microba, Idera Pharmaceuticals, and Merck within the past two years. GB has SRA with Palleon Pharmaceuticals, Olink Proteomics, InterVenn Biosciences and formerly with Takeda Oncology; she consults for Merck and InterVenn and served on the SAB and a steering committee for Nektar Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pickering, Aiyetan, Xu, Mitchell, Rice, Najjar, Markowitz, Ebert, Brown, Tapia-Rico, Frederick, Cong, Serie, Lindpaintner, Schwarz and Boland.)

Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT. Our statement has been created on the basis of clinical demand and concerns regarding the precipitation of hormonal crises. A formal literature review was conducted to identify available studies. A total of 19 Australian and New Zealand experts in the fields of medical oncology, nuclear medicine, anaesthetics, and endocrinology collaborated on this consensus statement. The main focus is on carcinoid crises. Other hormonal crises seen in patients with functional pancreatic NENs are addressed briefly. These recommendations are relevant to PRRT centres internationally and should be tailored to local experience and available resources., (© 2022 S. Karger AG, Basel.)

Purpose for Review: This perspective piece aims to understand the impacts of the COVID-19 pandemic on the field of oncology, exploring the factors provoking a fall in cancer diagnostic rates, interruption of cancer screening programmes, disruption of oncological treatment and adjuvant care, and the necessary adaption oncological practice has undergone (and will be required to undergo) post-pandemic, including the shift to digital consultations., Recent Findings: During the COVID-19 pandemic, the field of oncological research has faced significant challenges. Yet, innovation has prevailed with new developments being made across the globe. Looking to the future of oncology, this piece will also suggest potential solutions to overcome the late-stage ramifications of the COVID-19 pandemic. The COVID-19 pandemic has triggered a global health crisis, the ramifications of which have reached every corner of the world and overwhelmed already overburdened healthcare systems. However, we are still yet to see the full domino effect of the pandemic as it continues to reveal and exacerbate pre-existing weaknesses in healthcare systems across the world., (© 2022. The Author(s).)

Colorectal cancer (CRC) incidence in young adults is rising. Identifying genetic risk factors is fundamental for the clinical management of patients and their families. This study aimed to identify clinically significant germline variants among young adults with CRC. Whole-exome sequencing data of blood-derived DNA from 133 unrelated young CRC patients (<55 years of age) underwent a comprehensive analysis of 133 cancer-predisposition/implicated genes. All patient tumors were evaluated for mismatch repair deficiency (dMMR). Among 133 patients (aged 16-54 years), 15% (20/133) had clinically actionable pathogenic or likely pathogenic (P/LP) variants in at least 1 well established cancer-predisposing gene: dMMR genes (6), MUTYH [bi-allelic (2), mono-allelic (3)], RNF43 (1), BMPR1A (1), BRCA2 (4), ATM (1), RAD51C (1), and BRIP1 (1). Five patients (4%) had variants in genes implicated in cancer but where the significance of germline variants in CRC risk is uncertain: GATA2 (1), ERCC2 (mono-allelic) (1), ERCC4 (mono-allelic) (1), CFTR (2). Fourteen (11%) had dMMR tumors. Eighteen (14%) reported a first-degree relative with CRC, but only three of these carried P/LP variants. Three patients with variants in polyposis-associated genes showed no polyposis (one each in MUTYH [bi-allelic], RNF43, and BMPR1A). Approximately one in five young adults in our series carried at least one P/LP variant in a cancer-predisposing/implicated gene; 80% of these variants are currently considered clinically actionable in a familial cancer setting. Family history and phenotype have limitations for genetic risk prediction; therefore multigene panel testing and genetic counseling are warranted for all young adults with CRC regardless of those two factors., (© 2021 Wiley Periodicals LLC.)

Non-cutaneous melanomas (mucosal, uveal, leptomeningeal, unknown primaries) represent around 5-10 % of all melanoma diagnoses. Non-cutaneous melanomas demonstrate differences in tumour biology, generally present with more advanced stages and have an overall poorer prognosis compared to skin melanomas. The cornerstone of their treatment is surgery followed by radiotherapy in some cases. Unfortunately, in many of these patients their melanoma will recur. Adjuvant therapy for non-cutaneous melanomas remains controversial. To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit; the two randomised positive trials were criticized for methodological reasons, small sample size and conflicting results. The aim of this review is to assess the current evidence on systemic adjuvant treatments for high-risk resected non-cutaneous melanomas. We also provide a summary table with the currently recruiting clinical trials in these settings and we discuss some strategies to improve trial design in this particularly niche area of oncology., (Copyright © 2021. Published by Elsevier B.V.)

Primary appendiceal neoplasms (ANs) comprise a heterogeneous group of tumors. The pathology and classification of ANs have been controversial, and thus, a new classification of these neoplasms was published in the World Health Organization (WHO) classification of tumors (5th edition, 2019). However, immunohistochemistry (IHC) features of epithelial ANs are not explained in this edition and the limited data on the molecular pathology of these tumors shows inconsistent findings in various studies. It would be useful to identify biomarkers appropriate for each subtype to better aid in treatment selection. Therefore, we reviewed the literature to investigate what is known of the molecular pathology and IHC features of the most frequently diagnosed pathological subtypes of epithelial ANs based on the recent classification. The inconsistencies in research findings regarding the IHC features and molecular pathology of ANs could be due to differences in the number of samples and their collection and preparation as well as to the lack of a universally accepted classification system for these neoplasms. However, the literature shows that epithelial ANs typically stain positive for MUC2, CK20, and CDX2 and that the expression of SATB2 protein could be used as a biomarker for appendix tumor origin. Low-grade appendiceal mucinous neoplasms tend to have mutations in KRAS and GNAS but are usually wild-type for BRAF , APC , and P53 . Conversely, appendiceal adenocarcinomas are frequently found with mutations in KRAS , GNAS , P53 , PIK3CA , and APC , and have significant nuclear expression of β-catenin, loss of nuclear or nuclear and cytoplasmic expression of SMAD4, and loss of cytoplasmic membranous expression of E-cadherin. Goblet cell carcinomas (GCCs) typically stain positive for keratin and mucin markers and are frequently mutated in P53 and chromatin-modifier genes, but they tend to be wild-type for KRAS , GNAS , APC , and PIK3CA. The expression of CK7 and SATB2 proteins is usually negative in appendiceal neuroendocrine neoplasms and they lack the mutations in common cancer-associated genes including APC , BRAF , SMAD4 , and PIK3C. The available data suggest that GCCs have distinct molecular and immunohistochemical features and that they have characteristics more in common with adenocarcinoma than classical neuroendocrine tumors. In addition, MSI does not seem to have a role in the pathogenesis of epithelial ANs because they are rarely detected in these tumors. Finally, hereditary predisposition may have a role in the development of ANs because heterozygous CTNNβ1 , NOTCH1, and NOTCH4 germline mutations have recently been identified in low and high grades ANs.

Background: Colorectal cancer (CRC) is rising in incidence in young adults, and this observation is currently unexplained. We investigated whether having a personal history of type 2 diabetes mellitus (T2D) was a potential risk factor for young-onset colorectal cancer (YOCRC)., Methods: The South Australian Young Onset (SAYO) CRC study is a series of young adults with CRC below age 55. Ninety unrelated YOCRC cases were recruited to the study. Personal history and detailed family history of T2D were obtained at face-to-face interview and confirmed from medical records. Whole exome sequencing was conducted on germline DNA from each CRC case. Controls for personal history studies of T2D were 240 patients with proven clear colonoscopies and no known CRC predispositions., Results: The median age of YOCRC cases was 44 years (18-54) and of controls was 45 years (18-54), and 53% of both cases and controls were females (P = 0.99). Left-sided (distal) CRC was seen in 67/89 (75%) of cases. A personal history of T2D was confirmed in 17/90 (19%) YOCRC patients compared with controls (12/240, 5%; P < 0.001; odds ratio = 4.4; 95% confidence interval, 2.0-9.7). YOCRC patients frequently reported at least one first-degree relative with T2D (32/85, 38%). Ten of 87 (12%) of YOCRC cases had CRC-related pathogenic germline variants, however, no pathogenic variants in familial diabetes-associated genes were seen., Conclusions: Though the mechanism remains unclear, our observations suggest that there is enrichment for personal history of T2D in YOCRC patients., Impact: A diagnosis of T2D could therefore potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate., (© 2020 John Wiley & Sons Australia, Ltd.)

Objectives: The study aimed to examine the incidence and mortality rates of appendiceal neoplasms (ANs) in Australia., Methods: A retrospective analysis was performed on national data obtained from the Australian Institute of Health and Welfare (AIHW) from 1982 to 2013. Changes to the incidence, and the cancer-specific mortality following the diagnosis of ANs were analyzed over this time period, with stratification performed for histological subtype, gender, and age groups (<50y and ≥50y)., Results: Incidence and mortality rates of ANs increased significantly across both genders and age groups. Incidence rates increased by 415%, from 0.40/100 000 population in 1982 to 2.06/100 000 in 2013. Overall mortality rates increased by 130%, from 0.057/100 000 during 1982-1985 to 0.131/100 000 during 2010-2013. Controlling for age group and gender, the incidence rates increased by 20% every four years (Incidence rate ratio (IRR) = 1.20, 95% confidence interval (CI): 1.17, 1.23, global P value<0.0001), and controlling for age, the mortality rates increased by 8% every four years (IRR = 1.08, 95% CI: 1.00, 1.17, global P-value = 0.0401)., Conclusion: The increasing use of CT scanning, improvements in pathological assessment of the appendix, and the growing aging population may have contributed in part to the apparent rise in the incidence of ANs.

Myxopapillary ependymoma (MPE) is a rare glial tumour mainly located in the areas of the conus medullaris, cauda equina and filum terminale of the spinal cord. Ectopic MPE tends to behave more aggressively and distant metastases are often seen. Unfortunately, no standard treatment options are established as only small series of treated patients and a few reported cases are available in the literature. We report the case of a 25-year-old woman who was initially diagnosed with a metastatic MPE, with multiple bilateral lung metastases. She was treated with an investigational monoclonal antibody antiprogrammed cell death protein 1, called tislelizumab (BGB-A317), following surgical resection of the perisacral primary mass. The response was long-lasting and side effects nil. Immunotherapy is a treatment modality to be considered in patients with rare tumours., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Monepantel is an approved veterinary anthelmintic with a strong safety profile. Preclinical evidence suggests novel mTOR pathway-associated anticancer activity. An open-label Phase I trial assessed tolerability, pharmacokinetics, pharmacodynamics and PET-CT imaging following oral Zolvix ® monepantel administration to adults with treatment refractory, progressing and unresectable solid tumors., Methods: Subjects were scheduled to daily home-based monepantel administration for 28 days in a 3 + 3 dose escalation study (5.0, 25.0 and 62.5 mg/kg bw)., Results: Of 41 reported drug-related AEs, 68% were Grade 1 and 24% were Grade 2; 35 AEs related to gastrointestinal effects including very poor palatability. DLT and MTD could not be determined due to early termination. Myelosuppression was not observed at the lowest level tested. Three of four Cohort 1 subjects had reduced mTOR pathway marker p-RPS6KB1 levels in PBMCs and achieved RECISTv1.1 SD by CT; one had progressive bony metastases by FDG-PET. One subject recorded PD on day 28, correlating with no detectable plasma monepantel from day 7. Monepantel sulfone dominated monepantel in pharmacokinetics. Both Cohort 2 subjects withdrew early due to AEs and the trial was terminated., Conclusions: Short-term 5 mg/kg bw monepantel administration provides a combined steady-state trough plasma monepantel and monepantel sulfone concentration of 0.5 μM. Gastrointestinal AEs including very poor palatability are concerning and suggested to be resolved by future drug product reformulation. RECISTv1.1, p-RPS6KB1 and plasma tumor marker outcomes provide preliminary evidence of anticancer activity.

Despite the increasing incidence of metastatic melanoma in the older population, there are relatively limited data for those older than 75 years of age. Elderly patients are often under-represented in clinical trials. In addition, elderly patients in trials often have a lower Eastern Cooperative Oncology Group score and fewer comorbidities and may thus not truly reflect the realities of day-to-day clinical practice. We present a case of a 95-year-old woman who had extensive and unresectable subcutaneous and dermal deposits of metastatic melanoma of her right leg, which caused oedema and reduced mobility. She was treated concurrently with pembrolizumab and radiotherapy to her leg lesions of melanoma. She has had an excellent response to treatment, with complete resolution of the subcutaneous and dermal metastatic deposits and has not developed any immune-related toxicities. Our experience demonstrates that anti-programmed-death-receptor-1 therapy can be given safely and effectively even in very elderly metastatic melanoma patients., Competing Interests: Competing interests: MPB’s institution has received honoraria for his attendance at melanoma advisory boards held by Merck, Sharp and Dohme., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite the increasing incidence of metastatic melanoma in the older population, there is relatively limited specific data surrounding the use of immunotherapy for the treatment of advanced melanoma for patients above the age of 65 years. To date, there has not been a prospective trial done to evaluate the safety and efficacy of using immunotherapy to treat older patients with advanced melanoma. Older patients are often under-represented in clinical trials. In addition, older patients in clinical trials may have lower Eastern Cooperative Oncology Group (ECOG) performance score and fewer co-morbidities, and thus trial data may not truly reflect the experience of treating older patients. The purpose of this descriptive review is to examine the efficacy and safety data of the three currently approved immune checkpoint inhibitors for advanced melanoma treatment in older patients. Our review of available data established that the efficacy and tolerability of immunotherapy in older patients are comparable to results seen in younger patients. However, a dedicated, prospective, randomised trial to assess the safety, tolerability, and quality-of-life parameters of immunotherapy in the older population would provide further insight on the value of these treatments.

Aim: To examine the cancer-specific outcomes for patients who experience immune-related adverse events requiring immunosuppression beyond corticosteroids., Methods: We performed a retrospective case series of patients between January 1, 2009 and April 1, 2018, across three metropolitan hospitals in Adelaide, South Australia. Eligible patients were identified from pharmacy records. Patients with a solid organ malignancy had discontinued checkpoint inhibitor therapy due to toxicity, and required immunosuppression in addition to corticosteroids to treat any immune-related adverse event., Results: From 3860 patient dispensation records of immunosuppressive medications, 19 eligible patients were identified. Eight received a CTLA-4 inhibitor, four a PD-1 inhibitor, five combination immunotherapy, and two remained blinded. Sixteen patients had melanoma and three had non-small cell lung cancer. Median time to treatment failure was 8.7 months, and median overall survival was 9.4 months. Of those evaluable, the objective response rate was 35%, while 53% had progressive disease. Four patients died due to complications of their irAE, while six died from progressive disease., Conclusion: Patients who received immunosuppression for checkpoint inhibitor therapy toxicity had variable outcomes. This in part reflects a heterogeneous population, and the evolution of irAE management over time. Several patients continued to derive a benefit after cessation of therapy despite the use of immunosuppressive medications; conversely, four died as a direct consequence of their irAE. Physicians should promptly introduce immunosuppressive therapy in patients not responding to corticosteroids to mitigate the risk of life-threatening adverse events, given that current evidence does not clearly demonstrate a detriment to cancer-specific outcomes., (© 2019 John Wiley & Sons Australia, Ltd.)

"Can I keep my dog while receiving chemotherapy?" "Can my cat sleep on my bed while I'm on treatment?" "What precautions should I take with my pets in order to avoid infections?"" I read that my dog could give me breast cancer, is that true?" "Do you have assistance therapy dogs at your chemotherapy day unit?" These are not uncommon questions from cancer patients in oncology/haematology consultation rooms. The answers to these questions however, are widely unknown among physicians. Pet ownership is thought to provide patients with both emotional and physical health benefits. However, owning pets may also pose health risks to immunocompromised patients through zoonotic transmission of disease. Some studies have also suggested that the ownership of domestic pets may increase the risk of developing some cancers. But what is the evidence behind these claims? This paper presents the results of a literature review of a variety of scientific literature about pet ownership as a potential risk factor for suffering cancer, zoonotic diseases and the immunocompromised, and animal-assisted-therapy in cancer patients., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: For metastatic colorectal cancer, previous reports have described differences in biology and outcome, including response to biologic agents, based on whether the primary tumor is right- or left-sided. We explored the molecular markers from the AGITG MAX trial., Patients and Methods: The AGITG MAX trial was a randomized study comparing capecitabine versus capecitabine + bevacizumab versus capecitabine + bevacizumab + mitomycin C as first-line therapy in advanced colorectal cancer. Patients were classified as having right-sided (caecum to transverse colon) or left-sided (descending colon to rectum) disease according to anatomic location. Baseline characteristics and previously described molecular profiles were compared by side of primary tumor. Survival outcomes were analyzed by the Kaplan-Meier approach and proportional hazards regression modeling., Results: Among the 471 patients, the location of primary tumor was known in 440 patients (93%). Molecular profile was known in 298 patients (63%). Twenty-eight percent had right-sided primary tumors. Major differences between right and left are as follows: female 49% versus 33% (P < .01), BRAF mutant 16% versus 3.5% (P ≤ .001), and phosphatase and tensin homolog (PTEN) loss 27.6% versus 53% (P = .01). There were no differences in RAS mutation, PIK3CA mutation, or high versus low expression of assessed angiogenic markers. Right-sided primary lesion predicted a poor outcome for median overall survival: right-sided disease 13.2 months versus left-sided disease 20 months (P = .001; hazard ratio [HR] = 0.67; 95% confidence interval [CI], 0.53-0.85), but not for progression-free survival (HR 0.96; 95% CI, 0.78-1.20). The relative treatment effect did not differ significantly according to location of primary tumor: right primary tumor HR (bevacizumab containing arm vs. capecitabine monotherapy arm) was 0.82 (95% CI, 0.54-1.22), and left primary HR (bevacizumab containing arm vs. capecitabine monotherapy arm) was 0.51 (95% CI, 0.4-0.63) (interaction P = .10)., Conclusion: There are more negative prognostic factors in patients with right-sided primary tumors, in particular high BRAF mutations, and these patients have inferior overall survival compared to those with a left-sided primary tumor. There was no suggestion that side of primary site had any impact on bevacizumab effect on progression-free survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Peptide receptor radionuclide therapy (PRRT) is an important therapeutic option for somatostatin receptor (SSTR) positive metastatic and/or inoperable neuroendocrine tumours (NETs). However, in patients with poorly controlled carcinoid syndrome, it may lead to an acute flare of carcinoid symptoms or even carcinoid crisis. We report seven patients who received PRRT with ( 177 Lu-DOTA 0 , Tyr 3 ) octreotate ( 177 Lu-octreotate-LuTate) across two Australian tertiary medical institutions who developed acute flare of carcinoid symptoms/carcinoid crisis during/after PRRT. Cases were identified as high-risk due to previous history of carcinoid crises, high tumour burden and markedly elevated tumour markers. We propose a protocol to prevent and manage severe carcinoid symptoms in high-risk patients treated with PRRT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Atezolizumab is a fully humanized, engineered monoclonal antibody that specifically targets PD-L1, key molecule in the cancer-immunity pathway. Atezolizumab is currently approved for the treatment of metastatic non-small-cell lung cancer and advanced urothelial carcinomas. Areas covered: In this review, we will present the available data supporting the efficacy of atezolizumab for the treatment of metastatic colorectal cancer (mCRC). We will also provide an update on the ongoing/future clinical trials evaluating the role of atezolizumab for the treatment of CRC in different settings (alone or in combination with other checkpoint inhibitors and/or targeted therapies). So far, a small subgroup of mCRC (those with deficiency in mismatch repair - dMMR) appears to benefit significantly from checkpoint inhibitors. As expected, further research is needed to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and achieve better responses with minimal toxicities. Expert opinion: Interim analyses from ongoing early-phase studies in mCRC have shown encouraging activity of atezolizumab in combination with chemotherapy and/or targeted therapies, especially with MEK inhibitor cobimetinib. Within the next few years, this PD-L1 checkpoint inhibitor will likely be included as one of the treatment options for CRC, at least for patients with dMMR.

Objective: Brain metastasis is considered rare in metastatic colorectal cancer (mCRC); thus, surveillance imaging does not routinely include the brain. The reported incidence of brain metastases ranges from 0.6% to 3.2%., Methods: The South Australian mCRC Registry (SAmCRC) was analyzed to assess the number of patients presenting with brain metastasis during their lifetime. Due to small numbers, a descriptive analysis is presented., Results: Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis (1.4%). The clinical characteristics of those with brain metastasis were as follows: the median age was 65.3 years and 51% were female. Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation status of the tumor was known, the majority harbored a KRAS mutation (55%); 31 (53%) underwent craniotomy and 55 (93%) underwent whole-brain radiotherapy. The median survival time from diagnosis of brain metastasis was 4.2 months (95% confidence interval 2.9-5.5). Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy (8.5 months vs . 2.2 months, respectively). Data from the SAmCRC (a population-based registry) confirm that brain metastases are rare and the median time to development is approximately 2 years., Conclusions: Brain metastasis is a rare outcome in advanced CRC. Patients within the registry tended to be female, young in age, and harbored with higher rates of KRAS mutations. Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately, most patients with central nervous system involvement die from their extracranial disease.

Synovial metastasis is an unusual entity in solid tumours and only a few cases have been reported in the literature. We report a case of synovial metastasis of the knee in a young patient with progressive rectal adenocarcinoma and review previously published case reports of synovial involvement in advanced colorectal carcinomas. Synovial metastasis is just one of the multiple possibilities of differential diagnosis in patients with cancer suffering from monarthritis. Radiological tests (plain radiographs, bone scans, MRI of the joint and so forth) can be unspecific and cytological examination of the synovial fluid and/or histology of synovial biopsies is essential for a definitive diagnosis so as to tailor the best treatment for patients. Given the poor prognosis associated with these intra-articular secondaries, treatment is often limited to palliation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Metastatic colorectal cancer (mCRC) is the third leading cause of cancer deaths worldwide. As the population of the western world ages, the incidence of colorectal tumours among elderly patients is increasing and consequently so is the demand for treatments for elderly patients. Unfortunately, elderly patients (≥65 years) often go untreated and they are also under-represented in clinical trials. Yet there is some evidence suggesting that 'fit' elderly patients have similar outcomes and tolerance to chemotherapy treatment to their younger counterparts (although the definition of fitness in the elderly population is still a matter of debate). The evidence supporting the administration of new targeted therapies in patients older than 65 years is scarce and more research is needed. In this paper, we review all the available data concerning the use of targeted therapies for mCRC in patients older than 65 years of age and discuss the differences between this age subgroup and younger patients.

Introduction: Surgical resection of liver metastases from colorectal and neuroendocrine tumours has become a standard of care for resectable patients with isolated hepatic disease and good performance status, leading to extended survival in a carefully selected subgroup of these patients. However, the role of hepatic surgery in gastric and oesophageal liver metastases is controversial and not clearly defined. Areas covered:a systematic electronic literature search was performed to select the most representative evidence regarding hepatectomies in liver metastases from these two tumours. PubMed, Medline, Embase Ovid and Google Scholar databases were scanned for articles written in English and published in peer-reviewed journals between 1994 and May 2016. Expert commentary: Given the shortage of randomised studies and the limited number of patients in many of the studies discussed here, the evidence base for the use of hepatectomies in these settings is not strong. Thus, while the data for resections of gastric liver metastases may in particular seem encouraging, the results should be interpreted with caution.

Background: Although phase III studies have investigated the effect of adding bevacizumab to the 3-weekly capecitabine plus irinotecan (XELIRI) combination in the first-line treatment of metastatic colorectal cancer (mCRC), no phase III studies investigating the effects of adding bevacizumab to biweekly XELIRI have been published., Patients and Methods: A retrospective pooled analysis of 2 single-arm phase II studies was performed. Previously untreated patients with mCRC received irinotecan 175 mg/m(2) on day 1 followed by capecitabine 1,000 mg/m(2) twice daily on days 2-8 every 2 weeks with or without bevacizumab 5 mg/kg on day 1., Results: In total, 53 patients received XELIRI, and 46 patients received XELIRI plus bevacizumab. There was a statistically significant increase in partial response rate with XELIRI plus bevacizumab (63 vs. 26% for XELIRI; p = 0.0002) and overall response rate (67 vs. 32%; p = 0.0005). Median time to disease progression was significantly longer with XELIRI plus bevacizumab (12.3 vs. 9.0 months for XELIRI; p = 0.012); median overall survival did not differ significantly between treatments (23.7 vs. 19.3 months; p = 0.4997). The proportion of patients experiencing at least 1 grade 3/4 adverse event was similar with both treatments (XELIRI, 47%; XELIRI plus bevacizumab, 44%)., Conclusion: This retrospective pooled analysis suggests that XELIRI plus bevacizumab has an acceptable tolerability profile and improves efficacy outcomes compared with XELIRI in the first-line treatment of mCRC., (© 2013 S. Karger GmbH, Freiburg.)