Introduction

In Australia in 2020, lung cancer represented 9.1% of all new cancer diagnoses.1 While lung cancer remains the deadliest cancer, accounting for 18% of cancer deaths in Australia last year, there remains reason for optimism with a range of systemic therapy developments across the spectrum of early to advanced disease.1

Lung cancer screening

Contrary to well established screening programmes aimed at early detection of bowel and breast cancer, data supporting the benefits of screening in lung cancer have only recently become available. Screening is one of the ‘hot topics’ in thoracic oncology at present, as signalled by a recent A$6.9 million commitment by the Australian government towards efforts to scope a national programme.2

The benefits of targeted lung cancer screening with low-dose computed tomography (CT) have been shown in smoking populations. The US National Lung Screening Trial (NLST) recruited 53 454 high-risk persons between 2002 and 2004 and randomised them to three annual screenings with low-dose CT or chest X-ray.3 A 20% reduction in lung cancer mortality (95% confidence interval (CI) 6.8–26.7; P = 0.004) was reported with low-dose CT, with rate of death from any cause also 6.7% lower (95% CI 1.2–13.5; P = 0.02). Published last year, the NELSON trial, a Dutch/Belgian study, enrolled 13 195 men aged 50–74 years and randomised them to a baseline screening CT and then imaging at 1, 3 and 5.5 years versus no screening.4 The cumulative rate ratio for lung cancer death at 10 years was 0.76 (95% CI 0.61–0.94, P = 0.01). Of further interest are preliminary results of the TAiwan Lung cancEr screening for Never smoker Trial (TALENT), which demonstrated a T0 lung cancer detection rate of 3.2% and 2.0% among patients aged 55–75 years with or without a family history of lung cancer, all of whom had no or minimal smoking history.5 This compared to T0 detection rates of 1.1% and 0.9% in smoker populations in NLST and NELSON respectively. While applicability of this study to the Australian population is unclear, especially as in Taiwan a greater proportion of lung cancers occur in never smokers along with differences in driver mutations, these are nonetheless thought provoking results. In Australia, 1 in 3 women and 1 in 10 men diagnosed with lung cancer are never-smokers.6

Early disease: neoadjuvant/adjuvant immunotherapy, EGFR mutant disease

Among patients with non-small-cell lung cancer (NSCLC) who present with localised disease amenable to surgical resection, relapse rates, unfortunately, remain high. For patients who undergo surgery for tumours ≥4 cm and/or node positivity, 4 cycles of platinum-doublet chemotherapy remain standard-of-care.

The IMpower-010 study is the first of the four similarly designed large randomised controlled trials (RCT) to report on adjuvant immunotherapy given following adjuvant chemotherapy. Patients with resected stage II–IIIA NSCLC received 3-weekly atezolizumab, a programmed death ligand-1 (PDL-1) inhibitor, for up to 16 cycles, or best supportive care. Disease-free survival (DFS) was greater for atezolizumab-treated patients among patients with ≥1% of tumour cells positive for PDL-1 on immunohistochemistry (hazard ratio (HR) 0.66; 95% CI 0.50–0.88).7 DFS of the intention-to-treat population also favoured atezolizumab (HR 0.81; 95% CI 0.67–0.99). Ongoing maturation of overall survival (OS) data will be informative.

Some surgical patients may be considered for neoadjuvant chemotherapy, such as those with a Pancoast tumour or large, potentially resectable tumours with the aim to down-stage and optimise surgical outcomes. Although tumour shrinkage with chemotherapy can be achieved, pathological complete responses (pCR) are uncommon. Preliminary results for the CheckMate 816 phase III, RCT of patients with stage IB-IIIA disease, have recently been presented showing a 24.0% pCR rate among patients who received neoadjuvant nivolumab, a programmed cell death protein-1 (PD-1) inhibitor, combined with chemotherapy, compared to 2.2% pCR rate among those who received chemotherapy alone.8, 9 The major pathological response rate, defined as ≤10% viable tumour, for combination chemotherapy plus nivolumab was 36.9%.9

Of particular interest in the early disease setting have been developments for management of patients with NSCLC harbouring somatic driver mutations of epidermal growth factor receptor (EGFR). ADAURA, a double-blind, phase III RCT, randomised patients with completely resected stage IB-IIIA EGFR-mutation positive NSCLC 1:1 to receive the third-generation tyrosine kinase inhibitor (TKI) osimertinib 80 mg PO daily or placebo for 3 years.10 Results reported at 24 months demonstrate significant improvement in DFS, the primary end-point (HR for disease recurrence/death 0.17; 99.06% CI 0.11–0.26). OS data remain immature, which raises questions around sequencing given osimertinib is currently considered first-line treatment in the advanced setting. Adjuvant osimertinib has recently received FDA approval, but is not Pharmaceutical Benefits Scheme (PBS) listed for this indication.

Locally advanced NSCLC

Approximately one-quarter of all patients diagnosed with NSCLC have locally advanced, stage III disease at diagnosis. For most patients, surgery will not be feasible, and thus for sufficiently fit patients the standard treatment paradigm has historically consisted of concurrent chemoradiotherapy with either carboplatin/paclitaxel or cisplatin/etoposide.11 While undertaken with ‘definitive’ intent, historically prognosis has remained poor, with ‘cure’ rate of approximately 20–25% at best.

The phase III PACIFIC RCT, which demonstrated both PFS (median 16.9 months vs 5.6 months; HR 0.55; 95% CI 0.45–0.68) as well as OS (47.5 months vs 29.1 months; HR 0.72; 95% CI 0.59–0.89) benefits with the addition of consolidation durvalumab, a PDL-1 inhibitor, following chemoradiotherapy for patients with stage III NSCLC, has been a game changer.12, 13 In this trial, good performance status patients (ECOG 0–1), who had not progressed following chemoradiotherapy, were randomised 2:1 to receive either 10 mg/kg i.v. durvalumab or placebo fortnightly for 12 months. Treatment with durvalumab was generally well tolerated with 3.4% of patients in the durvalumab arm experiencing grade 3–4 immune-related adverse events (irAE) and 8.2% requiring high-dose glucocorticoids for irAE. Grade 3–4 immune-related or radiation pneumonitis was recorded in 3.4% vs 2.6% of participants in the durvalumab and placebo arms respectively.14

Many questions remain for the management of this patient cohort. The importance of translational biomarker investigation will be critical to assist clinicians in identifying patients who are likely to respond well versus those who do not, particularly in the context of patients known to have EGFR mutations. In addition, the difficulty in discriminating between radiological changes apparent for immunotherapy-associated pneumonitis versus radiation-associated pneumonitis versus early recurrence presents new clinical challenges. In this regard, data from outside trial settings are also important, with any grade pneumonitis reportedly similar (10.6%) in PACIFIC-R,15 a large observational study incorporating ‘real world’ patient data from Europe, Israel and Australia; to the 12.6% rate noted in the original trial, though ongoing data collection will be informative.14

Metastatic NSCLC

Perhaps the most practice-changing developments in lung cancer in recent years have been advances for those with metastatic NSCLC with the advent of the immunotherapy and combination chemotherapy–immunotherapy era of the past decade, and a slew of targeted therapies for patients recognised to have driver molecular alterations.

‘No’ molecular alteration

For patients without a recognised targetable mutation, an increasingly diminishing fraction of all patients with metastatic NSCLC, treatment is largely dependent on PDL-1 status, scored as percentage tumour cells positive. Five-year OS was recently reported for KEYNOTE-024, which randomised patients with PDL-1 ≥ 50% to 4−6 cycles of platinum-based chemotherapy or pembrolizumab 200 mg i.v. q3/52 up to 35 cycles, with median OS 13.4 months (95% CI 9.4–18.3) and 26.3 months (95% CI 18.3–40.4) respectively.16 At 5 years, 31.9% of patients in the pembrolizumab group were still alive compared to 16.3% in the chemotherapy group. Single-agent pembrolizumab remains a good option for patients with high PDL-1 ≥50%, particularly those with lower disease volume who can afford to wait for the effect of immunotherapy.

For patients with PDL-1 <50% the landscape is more complex. For most reasonable performance status patients, treatment is with 4 cycles of platinum-doublet chemotherapy plus single-agent immunotherapy followed by maintenance chemo-immunotherapy (i.e. KEYNOTE-189 regimen: carboplatin/pemetrexed/pembrolizumab followed by pemetrexed/pembrolizumab if adenocarcinoma17) or immunotherapy (i.e. KEYNOTE-407 regimen: carboplatin/paclitaxel/pembrolizumab followed by pembrolizumab if squamous cell carcinoma (SCC)18). Alternatively, the quadruplet IMPower150 regimen carboplatin/paclitaxel/atezolizumab/bevacizumab is another option for patients with non-squamous disease, particularly for those patients requiring rapid disease control, or in later line settings for those with mutation-driven cancers who have progressed on TKI.19

Less or even no chemotherapy is a tantalising prospect on the basis of the recently reported CheckMate 9LA and CheckMate 227 trials. In CheckMate 9LA, superior OS was reported for patients who received nivolumab/ipilimumab (a CTLA-4 inhibitor) plus 2 cycles of platinum-doublet chemotherapy compared to those who received 4 cycles of chemotherapy with the regimen now PBS-approved for SCC.20 Benefit was apparent in all pre-defined PDL-1 expression subgroups, including PDL-1 <1% (HR 0.62 for survival, 95% CI 0.45–0.85). In CheckMate 227 patients who received ipilimumab (1 mg/kg i.v. 6 weekly)/nivolumab (3 mg/kg i.v. 2 weekly) until progression demonstrated superior OS compared to those who received 4 cycles of platinum-doublet chemotherapy (17.1 months, 95% CI 15.2–19.9 versus 13.9 months, 95% CI 12.2–15.1 across all patients, HR for death 0.79, 95% CI 0.65–0.96).21 However, such data raise several questions, including the use of chemotherapy-alone comparators that are no longer standard of care, relationship to varying PDL-1 cut-offs, and CheckMate 227 is not PBS listed.

Molecular alterations

All patients with adenocarcinoma should be tested for somatic driver mutations in EGFR, ALK and ROS1, at a minimum, as PBS-listed targeted therapies exist for each. Such testing should be reflex in non-squamous NSCLC, that is, initiated by the pathologist to minimise delays in commencing treatment. Activating EGFR mutations (e.g. L858R or exon 19 deletion) are observed in approximately 15% of patients with adenocarcinoma in Australia,22 and are more frequent among never-smokers, females and those of East Asian ethnicity (with 20–76% frequency reported in Asia-Pacific cohorts23). First-line therapy with the third-generation EGFR TKI osimertinib is now standard for patients with activating mutations, which is generally well tolerated and associated with both better treatment of cranial nervous system (CNS) metastases and reduced CNS seeding than earlier generation TKI.24 For patients previously commenced on first or second generation TKI who develop a T790M resistance mutation osimertinib is recommended in the second-line setting.25 Among patients with adenocarcinoma, 3–7% will harbour an ALK translocation,26 for which first-line alectinib or brigatinib and second-line lorlatinib is routine through PBS. For patients with a ROS1 alteration, 1–2% of adenocarcinoma cases,27 crizotinib and entrectinib are available on PBS.

In Australia, in an early stage all histologies cohort and separately, a metastatic cohort excluding ALK, EGFR, ROS1 mutated patients, 21.8%28 and 42%29 respectively of patients have been reported to have a KRAS mutation. Until recently, KRAS has been considered an ‘undruggable’ target, with mutations more commonly noted among Caucasian and smoking populations.30 Several KRAS TKI are in development with activity against the most common subtype, G12C, including sotorasib, which has a response rate of approximately 30% and has received FDA approval.31

Numerous other molecular alterations are recognised to be significant amongst patients with metastatic lung adenocarcinoma (e.g. BRAF, RET, MET, NTRK, HER2, NRG1), many of which have targeted agents available that have been FDA-approved overseas, but are yet to receive PBS-listing in Australia, but may be available to self-fund through drug access programmes or on trials (Table 1). This raises challenges with respect to equity, given variation in the extent of molecular panel testing available by institution with some patients having to pay for testing as well as paying for non-PBS drugs unless there is a compassionate access or co-pay programme in place. To this end, data from the currently recruiting Thoracic Oncology Group of Australasia (TOGA) ASPIRATION trial, an observational cohort study that facilitates access to comprehensive genomic screening for newly diagnosed patients, will be informative.

Table 1. Recognised oncogenic driver mutations in metastatic lung adenocarcinoma and corresponding targeted therapies Driver mutation Mutation frequency Available targeted therapies† Efficacy ALK ~3–7%26 Alectinib, lorlatinib, crizotinib, brigatinib, entrectinib

ALEX trial:32

First-line alectinib: ORR 82.9% (95% CI 75.95–88.51), median PFS 34.8 months (95% CI 17.7–not able to be estimated)

J-ALEX trial:‡33

First-line alectinib: median PFS 34.1 months

ROS1 ~1–2%26 Crizotinib, entrectinib

PROFILE 1001 trial:34

Crizotinib: ORR 72% (95% CI 58–83%), median DOR 24.7 months (95% CI 15.2–45.3), median PFS 19.3 months (95% CI 15.2–39.1), median OS 51.4 months (95% CI 29.3–not reached)

EGFR ~15%22§

First generation: gefitinib, erlotinib

Second generation: afatinib

Third generation: osimertinib

FLAURA trial:24

First-line osimertinib: ORR 80%, median DOR 17.2 months (95% 13.8–22.0),35 median OS 38.6 months (95% CI 26.6–36.0)

RET ~1–2%36 Selpercatinib

LIBRETTO-001 trial:36

Pre-treated: ORR 64% (95% CI 54–73), median DOR 17.5 months (95% CI 12.0–could not be evaluated)

First line: ORR 85% (95% CI 70–94%)

BRAF

~1–5%

(50% BRAF V600E)37

Dabrafenib/trametinib, encorafenib/binimetinib

Phase II trial of dabrafenib/trametinib in BRAF V600E mutant metastatic NSCLC:37

Pre-treated: ORR 68.4% (95% CI 54.8–80.1), median PFS 10.2 (95% CI 6.9–16.7), median OS 18.2 months (95% CI 14.3–28.6 months)

First line: ORR 63.9% (95% CI 46.2–79.2%), median PFS 10.8 (95% CI 7.0–14.5 months), median OS 17.3 months (95% CI 12.3–40.2 months)

MET

MET exon-14 skipping mutations: 3% adenocarcinoma, up to 20% sarcomatoid NSCLC38

MET gene amplifications: 2–4% untreated¶ NSCLC38

Capmatinib, tepotinib, crizotinib

GEOMETRY mono-1 trial of capmatinib:38

MET exon 14 skipping mutation pre-treated: overall response 41% (95% CI 29–53%), median DOR 9.7 months (95% CI 5.6–13.0)

MET exon 14 skipping mutation untreated: overall response 68% (95% CI 48–84), median DOR 12.6 months (95% CI 5.6–could not be estimated)

MET gene amplifications (gene copy number ≥10) pre-treated: overall response 29% (95% CI 19–41)

MET gene amplifications (gene copy number ≥10) untreated: overall response 41% (95% CI 16–68)

NTRK <1% Larotrectinib, entrectinib

Pooled analysis of 54 adults with TRK fusion-positive metastatic solid tumours treated with entrectinib in STARTRK-2/-1/ALKA-372-001 trials:39

ORR (all tumour types) 57% (95% CI 43–71%), median DOR 10.4 months (95% CI 7.1–not evaluable)

CI, confidence interval; DOR, duration of response; NSCLC, non-small-cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival. Small-cell lung cancer

Small-cell lung cancer (SCLC) accounts for 12–15% of lung cancer cases overall, with most patients diagnosed with extensive-stage (ES-SCLC) disease at outset and prognosis historically dismal with 5-year OS rates in the order of 5%. While this is typically a chemo-sensitive cancer initially, recurrence following initial treatment is common and often rapid. For the past 20 years or so, the standard-of-care for patients diagnosed with SCLC has consisted of 4 cycles of platinum-doublet chemotherapy with cisplatin or carboplatin/etoposide. For those with limited-stage SCLC, this is given in conjunction with concurrent thoracic radiotherapy and subsequently consideration given to suitability for prophylactic cranial irradiation.

Over the past few years, several phase III trials investigating the addition of immunotherapy to first-line platinum-doublet chemotherapy have been practice-changing for the management of ES-SCLC. IMPower 133, a double-blinded, placebo-controlled RCT demonstrated the addition of atezolizumab to 4 cycles of platinum-doublet chemotherapy followed by maintenance atezolizumab, achieved superior OS in patients with ES-SCLC compared to the same regimen with a placebo substitute (median OS 12.3 months atezolizumab arm vs 10.3 months placebo arm; HR 0.70; 95% CI 0.54–0.91).41 The CASPIAN trial, likewise demonstrated an OS benefit to the addition of durvalumab to standard-of-care first-line chemotherapy for ES-SCLC patients followed by durvalumab maintenance (median 13.0 months OS for durvalumab arm, 95% CI 11.5–14.8 months vs 10.3 months, 95% CI 9.3–11.2 months placebo arm).42 The addition of pembrolizumab to standard platinum-based chemotherapy followed by maintenance immunotherapy was investigated in the KEYNOTE-604 trial and met significance criteria for PFS (IA2 HR 0.75; 95% CI 0.61–9.91; P = 0.0023), but not OS.43 As of July 2020, atezolizumab has been PBS-listed for ES-SCLC.

While combination chemotherapy–immunotherapy has become the new standard of care for management of patients with ES-SCLC, many questions remain. At relapse following first-line therapy whether for limited or extensive disease, response is typically short-lived. For patients who demonstrate platinum-sensitivity and relapse more than 6 months following initial treatment, rechallenge with platinum-doublet chemotherapy may be considered, otherwise second-line chemotherapy has typically been with CAV (cyclophosphamide/doxorubicin/vincristine) or topotecan. Historically and overseas, topotecan has typically been the comparator agent in second-line SCLC trials, with a reported response rate of 24.3% among patients who relapse more than 2 months following initial therapy and median survival of 25 weeks, and has recently become available as a generic medicine in Australia in 2021.44 As with all sufficiently fit patients, due consideration should be given to enrolment in clinical trials, of which there are several investigating novel therapies, such as bi-specific T-cell engager (BiTE) approaches.

Mesothelioma

The incidence of mesothelioma in Australia is one of the highest globally and for 2020 Cancer Australia estimated 834 new cases would be diagnosed, 649 in men and 185 in females. This neoplasm arising from mesothelial surfaces, most commonly the pleura (80%), is typically associated with asbestos exposure. Histological classification consists of three main subtypes: epithelioid, sarcomatoid and mixed histology, with epithelioid portending the best prognosis.

Since 2002, the standard-of-care first-line therapy for mesothelioma has been platinum/pemetrexed chemotherapy following a landmark phase III RCT demonstrating superiority of cisplatin/pemetrexed compared to cisplatin alone (median OS 12.1 months vs 9.3 months; P = 0.020; HR 0.77).45 Of note, the addition of vitamin B12 and folate as supportive medications was associated with an increased median OS of 13.3 months and as such both form standard adjuncts.

In recent years, consideration has been given to the role of anti-vascular endothelial growth factor agents added to standard first-line platinum-doublet chemotherapy as well as the role of immunotherapy in both the first- and second-line settings. In 2016, the MAPS trial, an open-label, phase III RCT conducted in France, demonstrated an OS benefit with the addition of bevacizumab (an anti-angiogenic drug, at 15 mg/kg) to cisplatin/pemetrexed (median OS 18.8 months, 95% CI 15.9–22.6 months with bevacizumab vs 16.1 months, 95% CI 14.0–17.9 months without; HR 0.77; 95% CI 0.62–0.95; P = 0.0167).45 As such, although of modest benefit only, the addition of bevacizumab may be considered for suitable patients (e.g. who lack significant cardiac comorbidities or bleeding risks). This is more generally an option now that generic bevacizumab is available.

Regarding immunotherapy, the Checkmate 743 trial, a first-line open-label, phase III RCT randomised 1:1 605 individuals with pleural mesothelioma to either ipilimumab (1 mg/kg i.v. every 6 weeks) and nivolumab (3 mg/kg i.v. every 2 weeks) for up to 2 years, or up to 6 cycles of 3 weekly platinum (cisplatin 75 mg/m2 i.v. or carboplatin AUC5 i.v.) and pemetrexed (500 mg/m2 i.v.).46 At a pre-specified interim analysis point with median follow up of 29.7 months, immunotherapy demonstrated significantly increased median OS compared to chemotherapy (18.1 months, 95% CI 16.8–21.4 vs 14.1 months, 95% CI 12.4–16.2; HR 0.74; 95% CI 0.60–0.91; P = 0.0020). Of particular interest was the benefit seen amongst patients with non-epithelioid mesothelioma, which is typically less chemo-sensitive, with 54% reduction in risk of death compared to 14% reduction in epithelioid (non-epithelioid: median OS HR of 0.46; 95% CI 0.31–0.68; and epithelioid: median OS HR 0.86; 95% CI 0.69–1.08). The regimen was PBS listed in July 2021. Single-agent nivolumab has also recently been demonstrated as beneficial in the subsequent line setting compared to best supportive care, with the CONFIRM trial reporting superior investigator-assessed PFS (3.0 vs 1.8 months; HR 0.62; 95% CI 0.49–0.78; P < 0.001).47 Looking forward, trials investigating the role of addition of immunotherapy to standard platinum-based chemotherapy in the first-line setting will be of interest, such as the TOGA DREAM3R phase III trial, which builds on phase II data and will investigate the addition of durvalumab.48

Survivorship

Concomitant with systemic therapy advances as described, resulting in improved prognosis for many patients with metastatic NSCLC, has been emerging recognition that a subset of patients are fortunate to experience durable periods of disease control. Traditionally, survivorship care has referred to the physical, psychological and functional concerns of patients with early stage disease following tumour resection and adjuvant therapy, such as long-term medical sequelae of treatment (e.g. peripheral neuropathy, impacts on fertility) or fear of cancer recurrence. In 2019, a provocative editorial in the New England Journal of Medicine ‘Time to study metastatic cancer survivorship’ challenged this notion, suggesting that patients living with stable advanced cancer face other challenges and their real-world experience remains largely under studied.49

A recent special edition of the Journal of Cancer Survivorship, ‘Living with Incurable Cancer: Addressing Gaps in Cancer Survivorship’, has shone a spotlight on this issue, including a single-centre Australian study reporting the lived experience of 20 patients with metastatic NSCLC with 6 months or more stable disease on immunotherapy or targeted therapy. In this study, the median time since diagnosis of metastatic disease was 27 (range 10–108) months and half were never-smokers.50 Four main themes were identified: the experience of long-term treatment with immunotherapy or targeted therapy (some with ongoing treatment toxicities vs others very well and not identifying with ‘sick’ role); psychological challenges (e.g. living with prognostic uncertainty, fear of cancer progression, challenges associated with long-term clinical trial participation); desire for practical advice (e.g. returning to work, financial planning while prognosis uncertain); and support tailored to molecular subtype and treatment approach rather than a ‘one size fits all’ approach. A similar US-based study of patients receiving targeted therapy and their caregivers likewise highlights the challenge for such patients of living with stable yet incurable cancer ‘reflecting the foot-in-both-worlds experience’.51

Conclusion

It is heartening to report a mere ‘tip of the iceberg’ selection of recent practice-changing developments in lung cancer management. For example, we have not mentioned the variety of novel therapeutic strategies, such as antibody-drug conjugates, BiTE molecules, immunotherapy agents and novel targeted therapies that are being tested in early phase settings across Australia. In the diagnostic research space, as with other tumour types, the role of non-invasive, liquid biopsies, using circulating tumour DNA techniques is being investigated across a range of settings – to assist in early detection of minimal residual disease, and to track clonal evolution over time. In addition, there is increasing research focus on bringing TKI, with known efficacy for metastatic disease, forward to investigate utility in earlier disease settings.

Whilst the pace of development of novel systemic therapy approaches in the research setting is undoubtedly exciting, it is likewise important to consider the challenges for clinicians applying clinical trial data in ‘real world’ contexts. Funding complexities aside, other factors such as strict eligibility criteria can pose challenges for clinicians in extrapolating trial outcomes to the clinic. A population-based Australian study demonstrated >50% of patients ≥65 years with metastatic lung cancer would typically be excluded from clinical trial participation.52 In the Australian context geography may be a further consideration and hence the drive for tele-trial models to promote equity of access to clinical trial participation for rural patients.53 Hence the importance of collaborative groups such as the Lung Foundation and recently renamed lung cancer-specific TOGA trials group in continuing to advocate for the breadth of patient experience as far as the research and education agenda.

Finally, in 2021, it would be remiss not to acknowledge the relevance of COVID-19, with patients with lung cancer more likely to suffer serious morbidity and mortality.54 As has been reported elsewhere, there is concern regarding the potential for stage migration amongst new lung cancer diagnoses, due to the impact of COVID-19 related disruptions to healthcare delivery and consumer hesitancy.55 To conclude, the management of lung malignancies is a rapidly changing space and this can serve as an encouragement to the medical community and consumers alike, and yet much ground remains to be gained.

References

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