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Cancers
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Recent Advances in Trachea, Bronchus and Lung Cancer Management
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Recent Advances in Trachea, Bronchus and Lung Cancer Management

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: 15 September 2024 | Viewed by 12512

Special Issue Editors

Dr. Serafeim Chrysovalantis Kotoulas

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Guest Editor
Department of Pulmonology - Tuberculosis, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: immunotherapy; lung cancer; lung disease
Dr. Dionisios G. Spyratos

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Guest Editor
School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: pulmonary medicine; lung disease; lung cancer
Dr. Athanasia Pataka

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Guest Editor
Department of Respiratory Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: pulmonary medicine; sleep disorders; respiratory diseases; interstitial lung disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

According to the WHO, trachea, bronchus and lung cancer deaths rose to 1.8 million worldwide in 2019, remaining the leading cause of death from malignancies and the sixth most common cause of death overall. For upper-middle- and high-income countries, however, these occupied the fourth place.

Nevertheless, significant breakthroughs are made every year in their management.

The purpose of this Special Issue is to consolidate the most recent advances in trachea, bronchus and lung cancer management, from the moment of clinical suspicion to diagnosis and treatment options, aiming to provide a comprehensive and up-to-date tool which will assist clinicians in combatting this lethal disease.

Dr. Serafeim Chrysovalantis Kotoulas
Dr. Dionisios G. Spyratos
Dr. Athanasia Pataka
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • trachea, bronchus and lung cancer
  • non-small cell lung cancer (NSCLC)
  • small cell lung cancer (SCLC)
  • cancer management
  • clinical suspicion
  • diagnosis
  • treatment
  • prevention

Published Papers (11 papers)

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Research

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11 pages, 657 KiB  
Article
Efficacy and Safety of Tinzaparin Thromboprophylaxis in Lung Cancer Patients with High Thromboembolic Risk: A Prospective, Observational, Single-Center Cohort Study
by Marousa Kouvela, Maria Effrosyni Livanou, Dimitra T. Stefanou, Ioannis A. Vathiotis, Fotini Sarropoulou, Maria Grammoustianou, Evangelos Dimakakos and Nikolaos Syrigos
Cancers 2024, 16(7), 1442; https://doi.org/10.3390/cancers16071442 - 8 Apr 2024
Viewed by 462
Abstract
Background: The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk. Methods: This was a non-interventional, single-arm, prospective cohort study of lung cancer patients [...] Read more.
Background: The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk. Methods: This was a non-interventional, single-arm, prospective cohort study of lung cancer patients who received thromboprophylaxis with Tinzaparin 10.000 Anti-Xa IU in 0.5 mL, OD, used in current clinical practice. Enrolled ambulatory patients signed informed consent. Anti-Xa levels were tested. Results: In total, 140 patients were included in the study, of which 81.4% were males. The histology of the tumor was mainly adenocarcinoma. Lung cancer patients with high thrombotic risk based on tumor, patient, treatment, and laboratory-related factors were enrolled. Only one patient experienced a thrombotic event (0.7%), and 10 patients had bleeding events (7.1%), including only one major event. Anti-Xa levels measured at 10 days and 3 months did not differ significantly between patients who developed hemorrhagic events and those who did not (p = 0.26 and p = 0.32, respectively). Conclusion: Thromboprophylaxis with an intermediate Tinzaparin dose in high thrombotic-risk lung cancer patients is a safe and effective choice for the prevention of VTE. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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Review

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19 pages, 966 KiB  
Review
Neoadjuvant and Adjuvant Immunotherapy in Resectable NSCLC
by Evangelia Bogatsa, George Lazaridis, Chrysoula Stivanaki and Eleni Timotheadou
Cancers 2024, 16(9), 1619; https://doi.org/10.3390/cancers16091619 - 23 Apr 2024
Viewed by 381
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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19 pages, 614 KiB  
Review
Emerging Therapies in Kirsten Rat Sarcoma Virus (+) Non-Small-Cell Lung Cancer
by Anastasia Karachaliou, Elias Kotteas, Oraianthi Fiste and Konstantinos Syrigos
Cancers 2024, 16(8), 1447; https://doi.org/10.3390/cancers16081447 - 9 Apr 2024
Viewed by 648
Abstract
Kirsten rat sarcoma virus (KRAS) is the most frequently found oncogene in human cancers, including non-small-cell lung cancer (NSCLC). For many years, KRAS was considered “undruggable” due to its structure and difficult targeting. However, the discovery of the switch II region in the [...] Read more.
Kirsten rat sarcoma virus (KRAS) is the most frequently found oncogene in human cancers, including non-small-cell lung cancer (NSCLC). For many years, KRAS was considered “undruggable” due to its structure and difficult targeting. However, the discovery of the switch II region in the KRAS-G12C-mutated protein has changed the therapeutic landscape with the design and development of novel direct KRAS-G12C inhibitors. Sotorasib and adagrasib are FDA-approved targeted agents for pre-treated patients with KRAS-G12C-mutated NSCLC. Despite promising results, the efficacy of these novel inhibitors is limited by mechanisms of resistance. Ongoing studies are evaluating combination strategies for overcoming resistance. In this review, we summarize the biology of the KRAS protein and the characteristics of KRAS mutations. We then present current and emerging therapeutic approaches for targeting KRAS mutation subtypes intending to provide individualized treatment for lung cancer harboring this challenging driver mutation. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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13 pages, 868 KiB  
Review
Real-World Data and Evidence in Lung Cancer: A Review of Recent Developments
by Eleni Kokkotou, Maximilian Anagnostakis, Georgios Evangelou, Nikolaos K. Syrigos and Ioannis Gkiozos
Cancers 2024, 16(7), 1414; https://doi.org/10.3390/cancers16071414 - 4 Apr 2024
Viewed by 778
Abstract
Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects [...] Read more.
Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. The distinction between RWD and data derived from randomized clinical trials lies in the method of data collection, as RWD by definition are obtained at the point of care. Experimental designs resembling those used in traditional clinical trials can be utilized to generate RWD, thus offering multiple benefits including increased efficiency and a more equitable balance between internal and external validity. Real-world data can be utilized in the field of pharmacovigilance to facilitate the understanding of disease progression and to formulate external control groups. By utilizing prospectively collected RWD, it is feasible to conduct pragmatic clinical trials (PCTs) that can provide evidence to support randomized study designs and extend clinical research to the patient’s point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly and patients with poor performance status (PS), hepatitis, or human immunodeficiency virus, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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19 pages, 274 KiB  
Review
Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors following Disease Progression or Relapse
by Maria Effrosyni Livanou, Vasiliki Nikolaidou, Vasileios Skouras, Oraianthi Fiste and Elias Kotteas
Cancers 2024, 16(6), 1196; https://doi.org/10.3390/cancers16061196 - 18 Mar 2024
Viewed by 869
Abstract
Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options [...] Read more.
Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6–3.1 months and a Disease Control Rate (DCR) of 21.4–41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75–81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
12 pages, 1362 KiB  
Review
Robotic Bronchoscopy in Lung Cancer Diagnosis
by Vasileios S. Skouras, Ioannis Gkiozos, Andriani G. Charpidou and Konstantinos N. Syrigos
Cancers 2024, 16(6), 1179; https://doi.org/10.3390/cancers16061179 - 17 Mar 2024
Viewed by 788
Abstract
Background: The widespread use of chest CT has increased the number of detected pulmonary nodules. Nodules with intermediate risk of malignancy warrant further evaluation with PET-CT or sampling. Although sampling with conventional bronchoscopy presents lower complication rates compared to transthoracic needle biopsy (TTNB), [...] Read more.
Background: The widespread use of chest CT has increased the number of detected pulmonary nodules. Nodules with intermediate risk of malignancy warrant further evaluation with PET-CT or sampling. Although sampling with conventional bronchoscopy presents lower complication rates compared to transthoracic needle biopsy (TTNB), it is limited by the inability to reach distal airways. To overcome this shortcoming, a new bronchoscopic technique named robotic bronchoscopy (RB) has emerged. Methods: A literature review was used to clarify the rationale behind RB emergence, describe RB procedure, and summarize data regarding its efficacy and safety. Results: The FDA has approved three RB platforms for clinical use. RB is safe, presenting a mortality and complication rate of 0% and 0–8.1%, respectively. Common complications include pneumothorax (0–5.7%) and minor bleeding (0–3.2%). However, its diagnostic yield remains lower than that of TTNB. Conclusions: RB is a promising bronchoscopic technique that aims to overcome the limitations of conventional bronchoscopy and improve upon the current techniques of guided bronchoscopy for the investigation of pulmonary nodules. Despite the lower complication rate, current evidence suggests a lower diagnostic yield compared to TTNB. Additional studies are required to adequately evaluate the role of RB in the diagnosis of pulmonary nodules. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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16 pages, 295 KiB  
Review
Lung NETs and GEPNETs: One Cancer with Different Origins or Two Distinct Cancers?
by Georgios Evangelou, Ioannis Vamvakaris, Anastasia Papafili, Maximilian Anagnostakis and Melpomeni Peppa
Cancers 2024, 16(6), 1177; https://doi.org/10.3390/cancers16061177 - 17 Mar 2024
Viewed by 951
Abstract
Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, [...] Read more.
Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, the role of EGFR in carcinogenesis, the presence of transcription factors, and the immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may improve our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
16 pages, 1258 KiB  
Review
The Gap of Health Inequalities Amongst Lung Cancer Patients of Different Socioeconomic Status: A Brief Reference to the Greek Reality
by Amalia Sofianidi, Alexandra Karadimou, Andriani Charpidou and Konstantinos N. Syrigos
Cancers 2024, 16(5), 906; https://doi.org/10.3390/cancers16050906 - 23 Feb 2024
Viewed by 1391
Abstract
Lung cancer treatment and patient care are constantly improving, but it remains doubtful whether this applies equally to all socioeconomic groups. It is nowadays well established that there are socioeconomic inequalities regarding lung cancer incidence, screening, effective treatment, overall survival, and prognosis. One [...] Read more.
Lung cancer treatment and patient care are constantly improving, but it remains doubtful whether this applies equally to all socioeconomic groups. It is nowadays well established that there are socioeconomic inequalities regarding lung cancer incidence, screening, effective treatment, overall survival, and prognosis. One of the key contributing factors to low socioeconomic status is low education. Low educational level is correlated with several factors, such as smoking habits, bad lifestyle behaviors, lower paid and unhealthier occupations, polluted neighborhoods, and genetic-familial risk, that lead to increased lung cancer incidence. The disparities regarding lung cancer care are further enhanced by stigma. On this basis and inspired by the gap in health equality among the Greek population, the Greek Society of Lung Cancer initiated a campaign, “MIND THE GAP”, to help increase awareness and minimize the gap associated with lung cancer, both in Greece and across Europe. The aim of this review is to explore the gap of health inequalities regarding lung cancer incidence and prognosis between patients of different SES and its root of causality. Key pivotal actions towards bridging this gap are reviewed as well. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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15 pages, 286 KiB  
Review
Artificial Intelligence-Based Treatment Decisions: A New Era for NSCLC
by Oraianthi Fiste, Ioannis Gkiozos, Andriani Charpidou and Nikolaos K. Syrigos
Cancers 2024, 16(4), 831; https://doi.org/10.3390/cancers16040831 - 19 Feb 2024
Cited by 1 | Viewed by 1820
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. [...] Read more.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. Targeting oncogenic driver mutations and immune checkpoint inhibition has indeed revolutionized NSCLC treatment, yet there still remains the unmet need for robust and standardized predictive biomarkers to accurately inform clinical decisions. Artificial intelligence (AI) represents the computer-based science concerned with large datasets for complex problem-solving. Its concept has brought a paradigm shift in oncology considering its immense potential for improved diagnosis, treatment guidance, and prognosis. In this review, we present the current state of AI-driven applications on NSCLC management, with a particular focus on radiomics and pathomics, and critically discuss both the existing limitations and future directions in this field. The thoracic oncology community should not be discouraged by the likely long road of AI implementation into daily clinical practice, as its transformative impact on personalized treatment approaches is undeniable. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)

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8 pages, 237 KiB  
Commentary
Uncommon and Rare EGFR Mutations in Non-Small Cell Lung Cancer Patients with a Focus on Exon 20 Insertions and the Phase 3 PAPILLON Trial: The State of the Art
by Federico Pio Fabrizio, Ilaria Attili and Filippo de Marinis
Cancers 2024, 16(7), 1331; https://doi.org/10.3390/cancers16071331 - 29 Mar 2024
Viewed by 951
Abstract
Uncommon (ucEGFRmuts) and rare epidermal growth factor receptor (EGFR) mutations account for 10–15% of diagnosed cases and consist of a heterogeneous group represented by several clusters within exons 18–21 (e.g., exon 18 point mutations, exon 21 L861X, exon 20 S768I), as [...] Read more.
Uncommon (ucEGFRmuts) and rare epidermal growth factor receptor (EGFR) mutations account for 10–15% of diagnosed cases and consist of a heterogeneous group represented by several clusters within exons 18–21 (e.g., exon 18 point mutations, exon 21 L861X, exon 20 S768I), as well as exon 20 insertions (Ex20ins). Their incidence is under molecular and clinical investigation following recent findings that reported an increase of sensitivity and specificity of next-generation sequencing (NGS) methods. Consequently, their detection allows for the selection of emerging treatment options to significantly improve patients’ outcomes in these particular subgroups of EGFR-mutated advanced non-small cell lung cancer (NSCLC). Specifically, this commentary is focused on the notable progress of the Phase 3 PAPILLON study that showed primary efficacy results from amivantamab, a bispecific antibody with specific binding and affinity to extracellular domains of EGFR and MET, plus chemotherapy in the first-line setting for EGFR exon 20 insertion–mutated advanced or metastatic NSCLC patients, as compared with chemotherapy alone, thus becoming the new standard of care in this group of patients. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
18 pages, 2985 KiB  
Systematic Review
AI-Driven Models for Diagnosing and Predicting Outcomes in Lung Cancer: A Systematic Review and Meta-Analysis
by Mohammed Kanan, Hajar Alharbi, Nawaf Alotaibi, Lubna Almasuood, Shahad Aljoaid, Tuqa Alharbi, Leen Albraik, Wojod Alothman, Hadeel Aljohani, Aghnar Alzahrani, Sadeem Alqahtani, Razan Kalantan, Raghad Althomali, Maram Alameen and Ahdab Mufti
Cancers 2024, 16(3), 674; https://doi.org/10.3390/cancers16030674 - 5 Feb 2024
Viewed by 2685
Abstract
(1) Background: Lung cancer’s high mortality due to late diagnosis highlights a need for early detection strategies. Artificial intelligence (AI) in healthcare, particularly for lung cancer, offers promise by analyzing medical data for early identification and personalized treatment. This systematic review evaluates AI’s [...] Read more.
(1) Background: Lung cancer’s high mortality due to late diagnosis highlights a need for early detection strategies. Artificial intelligence (AI) in healthcare, particularly for lung cancer, offers promise by analyzing medical data for early identification and personalized treatment. This systematic review evaluates AI’s performance in early lung cancer detection, analyzing its techniques, strengths, limitations, and comparative edge over traditional methods. (2) Methods: This systematic review and meta-analysis followed the PRISMA guidelines rigorously, outlining a comprehensive protocol and employing tailored search strategies across diverse databases. Two reviewers independently screened studies based on predefined criteria, ensuring the selection of high-quality data relevant to AI’s role in lung cancer detection. The extraction of key study details and performance metrics, followed by quality assessment, facilitated a robust analysis using R software (Version 4.3.0). The process, depicted via a PRISMA flow diagram, allowed for the meticulous evaluation and synthesis of the findings in this review. (3) Results: From 1024 records, 39 studies met the inclusion criteria, showcasing diverse AI model applications for lung cancer detection, emphasizing varying strengths among the studies. These findings underscore AI’s potential for early lung cancer diagnosis but highlight the need for standardization amidst study variations. The results demonstrate promising pooled sensitivity and specificity of 0.87, signifying AI’s accuracy in identifying true positives and negatives, despite the observed heterogeneity attributed to diverse study parameters. (4) Conclusions: AI demonstrates promise in early lung cancer detection, showing high accuracy levels in this systematic review. However, study variations underline the need for standardized protocols to fully leverage AI’s potential in revolutionizing early diagnosis, ultimately benefiting patients and healthcare professionals. As the field progresses, validated AI models from large-scale perspective studies will greatly benefit clinical practice and patient care in the future. Full article
(This article belongs to the Special Issue Recent Advances in Trachea, Bronchus and Lung Cancer Management)
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