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Simple Summary: Single small primary liver cancers are curable with treatments such as surgical resection, ablation, and liver transplant; however, many patients initially receive trans-arterial chemo-embolisation (TACE), which is generally not considered a curative treatment in itself, and often go on to receive further follow-up treatments. Little is known regarding the outcomes of such patients compared to those who receive upfront ablation. Our real-world multi-centre study demonstrates that key survival outcomes are similar between those initially undergoing TACE and those receiving ablation after controlling for other key clinical variables and allowing for subsequent individualised treatment selection. Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Little is known about the differences in liver cancer care between liver cancer referral centres, with and without an integrated liver transplant program. Even after adjusting for other important factors, such as tumour stage and patient characteristics, we found that liver transplant centres systematically used different local cancer treatments compared to non-transplant centres. Patients managed at liver transplant centres showed improved overall survival, which was evident even after considering the increased rates of transplantation. The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC), even in early stages, has been a fatal diagnosis and a leading death cause worldwide for decades. The aim of this review is to analyze the steps towards immunotherapy in the pre-, post-, and perioperative setting of resectable lung cancer while highlighting the challenges that have arisen and the future considerations to take into account in order to optimize the therapeutic results. Non-small cell lung cancer, even when diagnosed in early stages, has been linked with poor survival rates and distant recurrence patterns. Novel therapeutic approaches harnessing the immune system have been implemented in early stages, following the designated steps of advanced NSCLC treatment strategies. Immune-checkpoint inhibitor (ICI) regimens as monotherapy, combinational, or alongside chemotherapy have been intensely investigated as adjuvant, neoadjuvant, and, more recently, perioperative therapeutic strategies, representing pivotal milestones in the evolution of early lung cancer management while holding great potential for the future. The subject of current ongoing research is optimizing treatment outcomes for patient subsets with different needs and identifying biomarkers that could be predictive of response while translating the trials' endpoints to survival rates. The aim of this review is to discuss all current treatment options with the pros and cons of each, persistent challenges, and future perspectives on immunotherapy as illuminating the path to a new era for resectable NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cure is the goal of treatment in early primary liver cancer with surgical resection and ablation therapy being the two most common modalities used. This real-world multi-centre Australian study demonstrates that surgical treatment results in superior outcomes. We observed a significantly reduced risk of death from any cause and of recurrent liver cancer after controlling for factors such as initial tumour burden, liver disease severity and other medical comorbidities. Our study provides compelling evidence to recommend surgery for suitable patients to achieve the best possible outcomes. The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Earlier diagnosis is often advocated to prevent advanced cancer morbidity and death. Compelling evidence exists where this occurs. A major conundrum is the lack of supportive evidence for some cancers where more sensitive screening and early detection may not translate into reduced morbidity and mortality. Some early cancers do not advance to metastases and death, and thus may not endanger the patient during life, nor require treatment. Biological variants that are non-metastatic and non-lethal may exist. Distinguishing potentially 'fatal' cancers from 'non-fatal' cancers is fundamental for screening to selectively benefit, while avoiding unnecessary treatment. Immune control of cancer has evidential support, and may explain why some cancers progress, while others stay quiescent. The extent of immune system modulation of malignant behaviour could decisively influence cancer outcomes, including lethality. We advance an evidence-based, immune model, worthy of further research, potentially explaining cancer "overdiagnosis" and the susceptibility to recurrence, regression, and lethality. Even though clinically small 'early' cancers represent many millions of cells biologically, when removed surgically, these often never recur or regrow, nor reduce the individual's lifespan. However, some early cancers remain quiescent and indolent; while others grow and metastasize, threatening life. Distinguishing between these different clinical behaviours using clinical/pathological criteria is currently problematic. It is reported that many suspicious lesions and early cancers are being removed surgically that would not threaten the patient's life. This has been termed 'overdiagnosis', especially in the sphere of cancer screening. Although a controversial and emotive topic, it poses clinical and public health policy challenges. The diagnostic differentiation between 'non-lethal' and 'lethal' tumor forms is generally impossible. One perspective gathering evidential support is that a dynamic balance exists between the immune response and malignant processes governing 'lethality', where many more cancers are produced than become clinically significant due to the immune system preventing their progression. Higher medical screening "diagnosis" rates may reflect lead-time effects, with more 'non-progressing' cancers detected when an early immune-cancer interaction is occurring. We present a model for this immune-cancer interaction and review 'excess' or 'overdiagnosis' claims that accompany increasingly sensitive diagnostic and screening technologies. We consider that immune tools should be incorporated into future research, with potential for immune system modulation for some early cancers. [ABSTRACT FROM AUTHOR]

Long-term outcomes in breast cancer patients differ based on the molecular subtype, with HER2-E being the most aggressive one. Advances in clinical practice have dramatically shifted HER2+ breast cancer prognosis. Risk adapted strategies to individualize therapies are necessary. De-escalation approaches have been encouraged based on the risks of clinical-pathological factors. Molecular gene subtyping could further accurately define HER2 addicted tumours that are sensitive to anti-HER2 therapies, thus sparing unnecessary treatments. The transition from immunochemistry to molecular profiling in HER2+ breast cancer is discussed.