Major breakthroughs in lung cancer adjuvant treatment: Looking beyond the horizon.

We are witnessing a silent revolution in the treatment of early stage non-small cell lung cancer (NSCLC), with a series of practice-changing clinical trials enriching the therapeutic perspectives of lung cancer patients with potentially curable disease. The ADAURA study marked the advent of precision medicine and biomarker testing to the early stages setting. The IMPower-010 trial interrupted the negative trend of adjuvant lung cancer immunotherapy, paving the way to the application of immune-checkpoint inhibition in the resected disease. The ITACA trial definitively established no role for tailored adjuvant chemotherapy in NSCLC, while the Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease. Growing evidence is supporting MRD as effective adjuvant prognostic biomarker to stratify disease's recurrence risk after radical interventions and select best candidates to the adjuvant strategies. This work summarizes the recent major breakthroughs in lung cancer adjuvant treatment, and provides a snapshot of the current real-world scenario, discussing the upcoming challenges and opportunities featuring the clinical management of early stage NSCLC patients.

A systematic review of phase II trials exploring anti-PD-1/PD-L1 combinations in patients with solid tumors.

BACKGROUND: A high number of combinations of PD-1/PD-L1 inhibitors with other anti-cancer therapies are in clinical development. The usefulness of phase II trials in evaluating their efficacy and safety is unclear. MATERIALS AND METHODS: We performed a systematic search on PubMed and Cochrane Library for phase II trials of PD-1/PD-L1 inhibitors in combination with other anti-cancer therapies (systemic therapy and/or radiotherapy) published between January 1st 2018 and December 31st 2020. Study design, primary endpoint and main outcomes were registered for each paper. RESULTS: 119 articles reporting on 65 regimens were included in our analysis. Backbone agents were more frequently PD-1 inhibitors (pembrolizumab = 47, nivolumab = 41, camrelizumab = 3) followed by anti-PD-L1 (durvalumab = 19, atezolizumab = 6, avelumab = 3). Therapeutic partners were other immunotherapeutic agents (n = 46), targeted therapies (n = 40), chemotherapy (n = 22) or radiotherapy (n = 11). The majority of articles reported on single-arm trials (n = 87, 73%) and response rate was the most frequent primary endpoint (n = 69, 58%). Objective responses, registered in 109 (92%) articles, ranged between 0% and 91%. The incidence of grade 3 or higher treatment-related adverse events, clearly reported in 97 (82%) articles, spanned from 0 to 100%. Five combinations received regulatory approval by Food and Drug Administration or European Medicine Agency for 9 different indications, based on the results of a phase II trial (n = 3) or on a confirmatory phase III trial (n = 6). CONCLUSIONS: The landscape of phase II trials evaluating PD-1/PD-L1 inhibitors with other anticancer therapies is heterogeneous. Combinations of two immunotherapeutic agents have been the most investigated. Only a minority of indications (8%) granted regulatory approval.

Treatment stage migration and treatment sequences in patients with hepatocellular carcinoma: drawbacks and opportunities.

PURPOSE: This retrospective analysis focuses on treatment stage migration in patients with hepatocellular carcinoma (HCC) to identify successful treatment sequences in a large cohort of real-world patients. METHODS: 1369 HCC patients referred from January 1993 to January 2020 to the tertiary center of the Heidelberg University Hospital, Germany were analyzed for initial and subsequent treatment patterns, and overall survival. RESULTS: The most common initial treatment was transarterial chemoembolization (TACE, n = 455, 39.3%) followed by hepatic resection (n = 303, 26.1%) and systemic therapy (n = 200, 17.3%), whereas the most common 2nd treatment modality was liver transplantation (n = 215, 33.2%) followed by systemic therapy (n = 177, 27.3%) and TACE (n = 85, 13.1%). Kaplan-Meier analysis revealed by far the best prognosis for liver transplantation recipients (median overall survival not reached), followed by patients with hepatic resection (11.1 years). Patients receiving systemic therapy as their first treatment had the shortest median overall survival (1.7 years; P < 0.0001). When three or more treatment sequences preceded liver transplantation, patients had a significant shorter median overall survival (1st seq.: not reached; 2nd seq.: 12.4 years; 3rd seq.: 11.1 years; beyond 3 sequences: 5.5 years; P = 0.01). CONCLUSION: TACE was the most common initial intervention, whereas liver transplantation was the most frequent 2nd treatment. While liver transplantation and hepatic resection were associated with the best median overall survival, the timing of liver transplantation within the treatment sequence strongly affected median survival.

Acute lymphoblastic leukemia-like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients.

Mixed phenotype acute leukemia (MPAL) is a rare type of leukemia with a limited number of studies conducted to characterize its clinical spectrum and most importantly the best treatment modality. MPAL blasts show more than one phenotype either myeloid/monocytic with T- or B-lymphoid or extremely rare triple lineage associated phenotypic markers. This study aimed to characterize MPAL cases with special emphasis on comparing adult and pediatric age groups, exploring treatment regimens, and clinical outcome. Among 2571 acute leukemia patients, 102 MPAL cases fulfilling the 2008/2016 WHO diagnostic criteria of MPAL were recruited in the study. The incidence of MPAL was 4% of acute leukemia patients. Pediatric cases were 54 (53%) while adults were 48/102 (47%). Myeloid/B-lymphoid phenotype was found in 86/102 (84%), with BCR-ABL fusion gene transcript detected in 14/102(13.7%) patients. ALL-like treatment showed better response rates as compared with the myeloid based regimen (p = 0.001). MPAL behaves in a manner that resembles in clinical features, their lymphoid progenitor counterpart leukemias both in adults and pediatric patients with superior treatment response to ALL-like regimen, especially in adults.

Treatment-related mortality in children with cancer: Prevalence and risk factors.

AIM: Intensive treatment regimens have contributed to a marked increase in childhood cancer survival rates. Death due to treatment-related adverse effects becomes an increasingly important area to further improve overall survival. In this study, we examined 5-year survival in children with cancer to identify risk factors for treatment-related mortality (TRM). METHODS: All children (aged <18 years at diagnosis) diagnosed with cancer in 2 Dutch university hospitals between 2003 and 2013 were included, survival status was determined and causes of death were analysed. Various demographic and treatment factors were evaluated, for which a multivariable competing risks analysis was performed. RESULTS: A total of 1764 patients were included; overall 5-year survival was 78.6%. Of all 378 deaths, 81 (21.4%) were treatment-related, with infection being responsible for more than half of these deaths. Forty percent of TRM occurred in the first three months after initial diagnosis. Factors associated with TRM in the multivariable competing risks analysis were diagnosis of a haematological malignancy, age at diagnosis <1 year and receipt of allogeneic haematopoietic stem cell transplantation. In children suffering from haematological malignancies, TRM accounted for 56.3% of 103 deaths. CONCLUSION: Over one in five deaths in children with cancer death was related to treatment, mostly due to infection. In children suffering from a haematological malignancy, more children died due to their treatment than due to progression of their disease. To further increase overall survival, clinical and research focus should be placed on lowering TRM rates without compromising anti-tumour efficacy. The findings presented in this study might help identifying areas for improvement.

Attributable Failure of First-line Cancer Treatment and Incremental Costs Associated With Smoking by Patients With Cancer.

Importance: Previous studies have shown that continued smoking among patients with cancer can increase overall and cancer-specific mortality, risk for second primary cancer, and risk for toxic effects of cancer treatment. To our knowledge, there have been no efforts to estimate additional costs for cancer treatment attributed to smoking. Objective: To model attributable incremental costs of subsequent cancer treatment associated with continued smoking by patients with cancer. Design, Setting, and Participants: For this economic evaluation, a model was developed in 2018 using data from a 2014 US Surgeon General's report that considered expected failure rates of first-line cancer treatment in nonsmoking patients, smoking prevalence, odds ratio of first-line cancer treatment failure attributed to smoking compared with nonsmoking, and cost of cancer treatment after failure of first-line cancer treatment. Main Outcomes and Measures: Attributable failures of first-line cancer treatment and incremental cost for subsequent treatment associated with continued smoking among patients with cancer. Results: Attributable treatment failures were higher under conditions in which high first-line cure rates were expected in nonsmoking patients compared with conditions in which low cure rates were expected. Peak attributable failures occurred under the conditions in which expected cure rates among nonsmoking patients ranged from 50% to 65%. Under the conditions of a 30% expected treatment failure rate among nonsmoking patients, 20% smoking prevalence, 60% increased risk of failure of first-line cancer treatment, and $100 000 mean added cost of treating a first-line cancer treatment failure, the additional incremental cost per 1000 total patients was estimated to be $2.1 million, reflecting an additional cost of $10 678 per smoking patient. Extrapolation of cost to 1.6 million patients with cancer diagnosed annually reflects a potential $3.4 billion in incremental cost. Conclusions and Relevance: The findings suggest that continued smoking among patients with cancer and the increase in attributable first-line cancer treatment failure is associated with significant incremental costs for subsequent cancer treatments. Additional work appears to be needed to identify optimal methods to mitigate these incremental costs.

Use of treatment information from a state central cancer registry in prostate cancer research.

A method was developed to categorize prostate cancer treatments for epidemiologic and outcomes studies. A total of 60,497 prostate cancer cases from the Florida Cancer Data System diagnosed between 2001 and 2007 were used. The classification has the following properties. First, the treatments classified in the same group are clinically comparable and capture all prostate cancer treatments or combinations of treatments (exhaustive classification). Second, the grouping was set up in a way that each patient is captured in only 1 treatment category without leaving out any patient due to treatment type (mutually exclusive categories). The prostate cancer cases were initially categorized into 14 combinations of treatment, which were then collapsed into 8 broader groups in order to maintain a large sample size for all groups, with treatments remaining clinically comparable within a group.

[Assessment of functioning in patients with head and neck cancer based on the international classification of functioning, disability and health (ICF)]. / Beurteilung von Funktionsfähigkeit bei Patienten mit Kopf-Hals-Tumoren, auf Basis der Internationalen Klassifikation für Funktionsfähigkeit, Behinderung und Gesundheit (ICF).

The article approaches with the question how preservation of function after treatment of head and neck cancer (HNC) can be defined and measured across treatment approaches. On the basis of the "International Classification of Functioning, Disability and Health (ICF)" a series of efforts are summarized how all relevant aspects of the interdisciplinary team can be integrated into a common concept.Different efforts on the development, validation and implementation of ICF Core Sets for head and neck cancer (ICF-HNC) are discussed. The ICF-HNC covers organ-based problems with food ingestion, breathing, and speech, as well as psychosocial difficulties.Relationships between the ICF-HNC and well-established outcome measures are illustrated. This enables the user to integrate different aspects of functional outcome into a consolidated approach towards preservation/rehabilitation of functioning after HNC - applicable for a variety of treatment-approaches and health-professions.

Maintenance chemotherapy: an evolving and increasingly acceptable strategy in cancer management.

Individual randomized phase 3 trials and meta-analyses of previously published studies have provided support for the general concept of the clinical utility of extending the duration of antineoplastic drug therapy in an effort to prolong ("maintain") a favorable clinical state. This commentary briefly reviews data from several of these reports.