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Special Issue "New Advances in the Treatment of Resectable Non-small Cell Lung Cancer"

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A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Thoracic Oncology".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 16510

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Special Issue Editors

Dr. Francesco Facciolo

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Guest Editor

Thoracic Surgery Department, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
Interests: lung cancer; surgery; robotic surgery; minimally invasive thoracic surgery; lymphadenectomy

Dr. Luca Bertolaccini

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Guest Editor

Department of Thoracic Surgery - IEO, European Institute of Oncology IRCCS, Milan, IT, Italy
Interests: lung cancer surgery; biostatistics; methodology
Special Issues, Collections and Topics in MDPI journals

Dr. Federico Cappuzzo

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Guest Editor

Medical Oncology, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
Interests: lung cancer; target therapy; immunotherapy; clinical trials

Special Issue Information

Dear Colleagues,

Despite the evolution in non-small cell lung cancer treatment, the overall prognosis is still poor. In this context, lobectomy and radical lymphadenectomy remain the cornerstone of surgical treatment of resectable NSCLC. One of the most important prognostic factors remains the presence of lymph node involvement, particularly the presence of mediastinal nodal involvement, as demonstrated in the VIII TNM staging system edition with a clear prognosis stratification considering the presence of nodal metastases. Furthermore, correct intraoperative staging is mandatory to reach an actual pathological status of the disease. The recent approval of Osimertinib for resected EGFR-mutated NSCLC in an adjuvant setting has led to the hypothesis that other targeted therapies used in metastatic patients can also lead to improved early-stage outcomes of NSCLC. Indeed, in addition to surgical treatment, some target therapies are being tested in adjuvant settings with promising outcomes. Some trials are open which use these therapies in the neoadjuvant setting. For this Special Issue, we welcome manuscripts focusing on recent advancements in the preoperative staging, the surgical resection of NSCLC, and the role of the new medications approved as adjuvant and neoadjuvant therapies. We also welcome systematic reviews, original research, economic evaluation, and cost-effectiveness studies on this relevant topic.

Dr. Francesco Facciolo
Dr. Luca Bertolaccini
Dr. Federico Cappuzzo
Guest Editors

Manuscript Submission Information

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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. Current Oncology is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

early-stage NSCLC
lymphadenectomy
robotic surgery
adjuvant therapy
neoadjuvant therapy

Published Papers (10 papers)

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Research

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Open AccessArticle

The Effect of Lung Resection for NSCLC on Circulating Immune Cells: A Pilot Study

and

Jacqueline Y. Channon

Curr. Oncol. 2023, 30(5), 5116-5134; https://doi.org/10.3390/curroncol30050387 - 17 May 2023

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Abstract

This pilot study sought to evaluate the circulating levels of immune cells, particularly regulatory T-cell (Treg) subsets, before and after lung resection for non-small cell lung cancer. Twenty-five patients consented and had specimens collected. Initially, peripheral blood of 21 patients was collected for circulating immune cell studies. Two of these patients were excluded due to technical issues, leaving 19 patients for the analyses of circulating immune cells. Standard gating and high-dimensional unsupervised clustering flow cytometry analyses were performed. The blood, tumors and lymph nodes were analyzed via single-cell RNA and TCR sequencing for Treg analyses in a total of five patients (including four additional patients from the initial 21 patients). Standard gating flow cytometry revealed a transient increase in neutrophils immediately following surgery, with a variable neutrophil–lymphocyte ratio and a stable CD4–CD8 ratio. Unexpectedly, the total Treg and Treg subsets did not change with surgery with standard gating in short- or long-term follow-up. Similarly, unsupervised clustering of Tregs revealed a dominant cluster that was stable perioperatively and long-term. Two small FoxP3^hi clusters slightly increased following surgery. In the longer-term follow-up, these small FoxP3^hi Treg clusters were not identified, indicating that they were likely a response to surgery. Single-cell sequencing demonstrated six CD4+FoxP3+ clusters among the blood, tumors and lymph nodes. These clusters had a variable expression of FoxP3, and several were mainly, or only, present in tumor and lymph node tissue. As such, serial monitoring of circulating Tregs may be informative, but not completely reflective of the Tregs present in the tumor microenvironment. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Open AccessArticle

Trimodality Treatment of Superior Sulcus Non-Small Cell Lung Cancer: An Institutional Series of 47 Consecutive Patients

Witold Rzyman

Małgorzata Łazar-Poniatowska

and

Curr. Oncol. 2023, 30(5), 4551-4562; https://doi.org/10.3390/curroncol30050344 - 27 Apr 2023

Viewed by 929

Abstract

Objectives: Treatment of superior sulcus tumors (SST) using concurrent chemoradiation followed by surgery is a current standard. However, due to the rarity of this entity, clinical experience in its treatment remains scarce. Here, we present the results of a large consecutive series of patients treated with concurrent chemoradiation followed by surgery at a single academic institution. Materials and Methods: The study group included 48 patients with pathologically confirmed SST. The treatment schedule consisted of preoperative 6-MV photon-beam radiotherapy (45–66 Gy delivered in 25–33 fractions over 5–6.5 weeks) and concurrent two cycles of platinum-based chemotherapy. Five weeks after completion of chemoradiation, pulmonary and chest wall resection was performed. Results: From 2006 to 2018, 47 of 48 consecutive patients meeting protocol criteria underwent two cycles of cisplatin-based chemotherapy and concurrent radiotherapy (45–66 Gy) followed by pulmonary resection. One patient did not undergo surgery due to brain metastases that occurred during induction therapy. The median follow-up was 64.7 months. Chemoradiation was well tolerated, with no toxicity-related deaths. Twenty-one patients (44%) developed grade 3–4 side effects, of which the most common was neutropenia (17 patients; 35.4%). Seventeen patients (36.2%) had postoperative complications, and 90-day mortality was 2.1%. Three- and five-year overall survival (OS) were 43.6% and 33.5%, respectively, and three- and five-year recurrence-free survival were 42.1% and 32.4%, respectively. Thirteen (27.7%) and 22 (46.8%) patients had a complete and major pathological response, respectively. Five-year OS in patients with complete tumor regression was 52.7% (95% CI 29.4–94.5). Predictive factors of long-term survival included age below 70 years, complete resection, pathological stage, and response to induction treatment. Conclusions: Chemoradiation followed by surgery is a relatively safe method with satisfactory outcomes. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Open AccessArticle

Disparities in Access to Thoracic Surgeons among Patients Receiving Lung Lobectomy in the United States

Sean J. Halloran

Christine E. Alvarado

and

Curr. Oncol. 2023, 30(3), 2801-2811; https://doi.org/10.3390/curroncol30030213 - 27 Feb 2023

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Abstract

Objective: Lung lobectomy is the standard of care for early-stage lung cancer. Studies have suggested improved outcomes associated with lobectomy performed by specialized thoracic surgery providers. We hypothesized that disparities would exist regarding access to thoracic surgeons among patients receiving lung lobectomy for cancer. Methods: The Premier Hospital Database was used to identify adult inpatients receiving lung lobectomy from 2009 to 2019. Patients were categorized as receiving their lobectomy from a thoracic surgeon, cardiovascular surgeon, or general surgeon. Sample-weighted multivariable analysis was performed to identify factors associated with provider type. Results: When adjusted for sampling, 121,711 patients were analyzed, including 71,709 (58.9%) who received lobectomy by a thoracic surgeon, 36,630 (30.1%) by a cardiovascular surgeon, and 13,373 (11.0%) by a general surgeon. Multivariable analysis showed that thoracic surgeon provider type was less likely with Black patients, Medicaid insurance, smaller hospital size, in the western region, and in rural areas. In addition, non-thoracic surgery specialty was less likely to perform minimally-invasive (MIS) lobectomy (cardiovascular OR 0.80, p < 0.001, general surgery OR 0.85, p = 0.003). Conclusions: In this nationally representative analysis, smaller, rural, non-teaching hospitals, and certain regions of the United States are less likely to receive lobectomy from a thoracic surgeon. Thoracic surgeon specialization is also independently associated with utilization of minimally invasive lobectomy. Combined, there are significant disparities in access to guideline-directed surgical care of patients receiving lung lobectomy. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Open AccessArticle

Disparate Time-to-Treatment and Varied Incidence of Actionable Non-Small Cell Lung Cancer Molecular Alterations in British Columbia: A Historical Cohort Study

Roy Avraham Hilzenrat

and

Curr. Oncol. 2023, 30(1), 145-156; https://doi.org/10.3390/curroncol30010012 - 22 Dec 2022

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Abstract

Background: non-small cell lung cancer (NSCLC) outcomes remain suboptimal for early-stage disease despite emerging advances in systemic therapy for the peri-operative period. Next-generation sequencing (NGS) identifies driver mutations for which targeted therapies have been developed that improve survival. The BC lung cancer screening program, which was initiated in May 2022, is expected to identify people with early and late stages of NSCLC. It is crucial to first understand the molecular epidemiology and patterns of time to initiate treatment across its five health authorities (HA) to optimize the delivery of care for NSCLC in BC. In this way, we may harness the benefits of targeted therapy for more people with NSCLC as novel advances in therapy continue to emerge. Objective: to compare (a) the frequency of actionable NSCLC molecular alterations among HAs and (b) the time to treatment initiation. Methods: a retrospective observational study was conducted with prospectively collected data from the BC CGL Database. Adults with late stage NSCLC who underwent targeted NGS were included for the time period from May 2020 to June 2021. Demographics, actionable molecular alterations, PDL-1 expression, and time to treatment across HAs were examined. Using appropriate statistical tests for comparison among HAs, p>0.05 was deemed significant. Results: 582 patients underwent NGS/IHC and analysis during the study period. The mean age was 71 (10.1), and 326 (56%) patients were female. A significantly higher proportion of all EGFRm+ were identified within Vancouver Coastal Health (VCHA) and Fraser Health Authority (FHA) compared to the other health authorities (p < 0.001). This also holds true for common sensitizing EGFRm+ alone (p < 0.001) and for sensitizing EGFRm+ when adjusted for females and smoker status (OR 0.75; 95% CI 0.62, 0.92; p = 0.005). Patients residing within the Northern, Interior, and Island HAs were less likely to receive treatment at the same rate as those in VCHA and FHA HAs. Conclusion: actionable NSCLC driver mutations are present in all regional HAs, with disparity noted in time to initiate treatment between HAs. This provides evidence for the importance of molecular testing for patients in all BC HAs to guide personalized and timely NSCLC treatment. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Review

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Open AccessReview

The Role of Sublobar Resection for the Surgical Treatment of Non-Small Cell Lung Cancer

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Curr. Oncol. 2023, 30(7), 7019-7030; https://doi.org/10.3390/curroncol30070509 - 22 Jul 2023

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Abstract

Lung cancer is the most common cancer killer in the world. The standard of care for surgical treatment of non-small cell lung cancer has been lobectomy. Recent studies have identified that sublobar resection has non-inferior survival rates compared to lobectomy, however. Sublobar resection may increase the number of patients who can tolerate surgery and reduce postoperative pulmonary decline. Sublobar resection appears to have equivalent results to surgery in patients with small, peripheral tumors and no lymph node disease. As the utilization of segmentectomy increases, there may be some centers that perform this operation more than other centers. Care must be taken to ensure that all patients have access to this modality. Future investigations should focus on examining the outcomes from segmentectomy as it is applied more widely. When employed on a broad scale, morbidity and survival rates should be monitored. As segmentectomy is performed more frequently, patients may experience improved postoperative quality of life while maintaining the same oncologic benefit. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Open AccessEditor’s ChoiceReview

Stage III Non-Small-Cell Lung Cancer: An Overview of Treatment Options

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Curr. Oncol. 2023, 30(3), 3160-3175; https://doi.org/10.3390/curroncol30030239 - 07 Mar 2023

Cited by 3 | Viewed by 2418

Abstract

Lung cancer is the second-most commonly diagnosed cancer and the leading cause of cancer death worldwide. The most common histological type is non-small-cell lung cancer, accounting for 85% of all lung cancer cases. About one out of three new cases of non-small-cell lung cancer are diagnosed at a locally advanced stage—mainly stage III—consisting of a widely heterogeneous group of patients presenting significant differences in terms of tumor volume, local diffusion, and lymph nodal involvement. Stage III NSCLC therapy is based on the pivotal role of multimodal treatment, including surgery, radiotherapy, and a wide-ranging option of systemic treatments. Radical surgery is indicated in the case of hilar lymphnodal involvement or single station mediastinal ipsilateral involvement, possibly after neoadjuvant chemotherapy; the best appropriate treatment for multistation mediastinal lymph node involvement still represents a matter of debate. Although the main scope of treatments in this setting is potentially curative, the overall survival rates are still poor, ranging from 36% to 26% and 13% in stages IIIA, IIIB, and IIIC, respectively. The aim of this article is to provide an up-to-date, comprehensive overview of the state-of-the-art treatments for stage III non-small-cell lung cancer. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

Open AccessReview

Immunotherapy for Metastatic Non-Small Cell Lung Cancer: Therapeutic Advances and Biomarkers

Giuseppina Rita Di Fazio

and

Curr. Oncol. 2023, 30(2), 2366-2387; https://doi.org/10.3390/curroncol30020181 - 16 Feb 2023

Cited by 4 | Viewed by 2473

Abstract

Immunotherapy has revolutionized the treatment paradigm of non-small cell lung cancer and improved patients’ prognosis. Immune checkpoint inhibitors have quickly become standard frontline treatment for metastatic non-oncogene addicted disease, either as a single agent or in combination strategies. However, only a few patients have long-term benefits, and most of them do not respond or develop progressive disease during treatment. Thus, the identification of reliable predictive and prognostic biomarkers remains crucial for patient selection and guiding therapeutic choices. In this review, we provide an overview of the current strategies, highlighting the main clinical challenges and novel potential biomarkers. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Other

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Open AccessBrief Report

Robotic Lobectomy without Complete Fissure for Non-Small Cell Lung Cancer: Technical Aspects and Perioperative Outcomes of the Tunnel Technique

Filippo Tommaso Gallina

Daniele Forcella

Enrico Melis

and

Francesco Facciolo

Curr. Oncol. 2023, 30(6), 5898-5905; https://doi.org/10.3390/curroncol30060441 - 19 Jun 2023

Viewed by 726

Abstract

Even though the use of the “fissure-last” technique in mini-invasive lobectomy with the fissureless condition is well accepted, in terms of perioperative outcomes, controversies still surround the hilar lymph node dissection. In this article, we reported a description of the robotic “tunnel technique” approach in the right upper lobectomy in the absence of a defined fissure. We then compared the short terms outcomes of 30 consecutive cases treated using this technique, with 30 patients treated using the “fissure last” VATS approach in the same institution, before the start of the robotic surgery program. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Open AccessCase Report

Acquired G2032R Resistance Mutation in ROS1 to Lorlatinib Therapy Detected with Liquid Biopsy

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Curr. Oncol. 2022, 29(9), 6628-6634; https://doi.org/10.3390/curroncol29090520 - 16 Sep 2022

Cited by 2 | Viewed by 1678

Abstract

Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK)/receptor tyrosine kinase inhibitor (ROS1), demonstrated efficacy in ROS1 positive (ROS1+) non-small cell lung cancer (NSCLC), although approval is currently limited to the treatment of ALK+ patients. However, lorlatinib-induced resistance mechanisms, and its efficacy against the resistance mutation G2032R in ROS1, respectively, have not yet been fully understood. Furthermore, concomitant tumor suppressor gene p53 (TP53) mutations occur in driver alteration positive NSCLC, but their prognostic contribution in the context of ROS1 inhibition remains unclear. Here we report a ROS1+ NSCLC patient who developed an on target G2032R resistance mutation during second-line lorlatinib treatment, indicating the lack of activity of lorlatinib against ROS1 G2032R. The resistance mutation was detected in plasma-derived ctDNA, signifying the clinical utility of liquid biopsies. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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Open AccessCase Report

Neoadjuvant Immunotherapy Combined with Chemotherapy for Local Advanced Non-Small-Cell Lung Cancer in a Patient with a History of Breast Cancer: A Case Report

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Curr. Oncol. 2022, 29(9), 6203-6210; https://doi.org/10.3390/curroncol29090487 - 29 Aug 2022

Cited by 1 | Viewed by 2320

Abstract

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1–2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy. Full article

(This article belongs to the Special Issue New Advances in the Treatment of Resectable Non-small Cell Lung Cancer)

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