key: cord-0819196-uyj4iske
authors: Arrieta, Oscar; Cardona, Andrés F.; Lara, Luis; Heredia, David; Barrón, Feliciano; Zatarain-Barrón, Zyanya Lucia; Lozano, Francisco; de Lima, Vladmir Cordeiro; Maldonado, Federico; Corona-Cruz, Francisco; Ramos, Maritza; Cabrera, Luis; Martin, Claudio; Corrales, Luis; Cuello, Mauricio; Arroyo-Hernández, Marisol; Aman, Enrique; Bacon, Ludwing; Baez, Renata; Benitez, Sergio; Botero, Antonio; Burotto, Mauricio; Caglevic, Christian; Ferraris, Gustavo; Freitas, Helano; Kaen, Diego Lucas; Lamot, Sebastián; Lyons, Gustavo; Mas, Luis; Mata, Andrea; Mathias, Clarissa; Muñoz, Alvaro; Patane, Ana Karina; Oblitas, George; Pino, Luis; Raez, Luis E.; Remon, Jordi; Rojas, Leonardo; Rolfo, Christian; Ruiz-Patiño, Alejandro; Samtani, Suraj; Viola, Lucia; Viteri, Santiago; Rosell, Rafael
title: Recommendations for detection, prioritization, and treatment of thoracic oncology patients during the COVID‐19 pandemic: The THOCOoP cooperative group
date: 2020-06-20
journal: Crit Rev Oncol Hematol
DOI: 10.1016/j.critrevonc.2020.103033
sha: b813d22069a29937c67d22991cae8d3874ec9a8e
doc_id: 819196
cord_uid: uyj4iske

The world currently faces a pandemic due to SARS-CoV-2. Relevant information has emerged regarding the higher risk of poor outcomes in lung cancer patients. As such, lung cancer patients must be prioritized in terms of prevention, detection and treatment. On May 7th, 45 experts in thoracic cancers from 11 different countries were invited to participate. A core panel of experts regarding thoracic oncology care amidst the pandemic gathered virtually, and a total of 60 initial recommendations were drafted based on available evidence. By May 16th, 44 experts had agreed to participate, and voted on each recommendation using a Delphi panel on a live voting event. Consensus was reached regarding the recommendations (>66% strongly agree/agree) for 57 questions. Strong consensus (>80% strongly agree/agree) was reached for 45 questions. Patients with lung cancer represent a particularly vulnerable population during this time. Special care must be taken to maintain treatment while avoiding exposure.

At the end of 2019, an outbreak of cases of atypical pneumonia was documented in China. The etiological agent was identified as SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2), and the disease was later known as COVID- 19 . From that initial site, COVID-19 has been transmitted in an accelerated J o u r n a l P r e -p r o o f

In another study of 105 cancer patients infected with COVID-19, reported in the 2020 AACR (Dai) the authors documented that lung cancer (22 cases corresponding to 21%) was the most common type of cancer in these series, followed by gastrointestinal, breast cancer, thyroid and hematological malignancies. Compared with a control group without malignancies of 536 patients with COVID-19, cancer patients had a higher risk of death, (OR = 2.34 P = 0.03), admission to the ICU (OR = 2.84, p = <0.01), development of serious symptoms (OR = 2.79, P = <0.1) and a higher probability of requiring mechanical ventilation [5] . Patients with lung cancer (n=22) included in this analysis represented the group with the second highest risk of complications, preceded only by hematological tumors, 4 died (18.8%), 6 (27.7%) were admitted to the ICU, 11 (50%) developed serious symptoms and 4 (18.8%) required mechanical ventilation. It has become seemingly clear that the COVID-19 pandemic is a global health problem, with increasing trends in most world regions, including America. As such, public policies have been implemented to counteract the effect on health systems.

Given the exponential increase in cases, hospitals have undergone considerable adaptations to offer care for patients with COVID-19, many of which require intensive care management. However, this refocusing has affected the care of patients with other serious diseases, including cancer care. In this regard, the urgent need for an adequate allocation and rational use of health systems is evident. The WHO states that "governments and health systems have an obligation to ensure, to the best of their ability, adequate provision of health care for al".

When this guarantee is flailing due to the current pandemic, the prioritization and rational use of resources should, to the best of our ability, be based upon evidence-based recommendations, particularly in time-sensitive conditions.

Delivery of standard-of-care for every patient at any moment should be the goal of all health providers. In the extreme case where saturated or collapsed health care systems challenge the status quo, a guideline of evidence-based recommendations which can be implemented provisionally without impacting longterm outcomes can aid decision making in the clinical setting. Furthermore, the access to potentially curative oncological surgeries has been reduced significantly. In Italy during the year of 2019, 371,000 cancer cases were diagnosed of which 80% were surgical candidates, and due to the COVID-19 pandemic, the number of surgeries has decreased in the last 30 days [6] .

This change and prioritization of health systems in the care of patients with COVID-19 has led professionals in the field of oncology to make decisions about which patients should receive oncological treatment. There are already some guidelines and consensus, for the attention of patients with cancer in multiple neoplasia.

These guidelines attempt to stratify patients according to risk categories to determine which patients may benefit the most from immediate therapy, and identify those whose clinical scenario will not change because of delayed treatment [7] .

This consensus is an effort by a multidisciplinary team of key opinion leaders who are currently faced with the challenge of providing standard-of-care for thoracic malignancies patients in the setting of overwhelmed or collapsed health systems.

These recommendations seek to propose management algorithms applicable to a population of patients with thoracic malignancies who might face delays or shortages due to the pandemic. In this way we seek to improve risk stratification, prioritize treatments and reduce complications in the current scenario. It is of utmost important to stress that these should only be considered when the scenario merits it, and not as routine choices. Furthermore, some of these treatment recommendations might be influenced by differences in socio-economic conditions and regulatory approvals of cancer drugs between countries as well as specific J o u r n a l P r e -p r o o f government restrictions during the COVID19 outbreak. Additionally, it is imperative that each clinical decision be made considering the baseline characteristics of the patient, including age and comorbidities.

On May 7th, 45 experts (medical oncology, surgeons, pulmonologists and radiotherapists) in thoracic cancers from 11 different countries were invited to participate in this project. By May 16th, 44 had agreed to participate, with a total of 44 experts for the final consensus.

A core of 6 experts gathered on May 9th in order to compose a set of clinically relevant questions in the COVID-19 pandemic setting. Each question was voted on in terms of relevance, application, frequency and available evidence. In the end, a total of 60 questions were considered for inclusion in the voting panel. All questions were thoroughly reviewed in the literature in order to compose an evidence-based recommendation for each. Questions in which evidence is scarce or controversial were only considered if they were highly clinically meaningful or frequent scenarios in the current setting. One question was deleted post-voting due to controversial evidence pertaining to the recommendation, leaving a total of 59 questions and recommendations.

A modified Delphi process was used to establish consensus about whether and how to adapt clinical care during this pandemic for patients with thoracic J o u r n a l P r e -p r o o f malignancies. On May 16th at 10 a.m., all invited experts who agreed to participate logged on to a live voting platform. During this meeting, participants had access to a voting tool in which they would state whether they agreed or disagreed with each recommendation. The Delphi scale for each recommendation included the following options "Totally disagree; strongly disagree; slightly disagree; neither agree nor disagree; slightly agree; agree; strongly agree; totally agree". During this session, a moderator read each question and displayed in a screen the recommendation, once this was done, panelists had 6 minutes to vote on an 8question section, once the voting was completed the moderator moved to the next section until all recommendations had been voted on.

Questions for the Delphi process were stratified according to 16 main categories which are all clinical scenarios frequently assessed in a thoracic oncology unit, or by any practice which routinely treats patients with thoracic cancers, all questions are summarized in Table 1 .

Once the voting was complete, all answers were categorized into three main categories for each recommendation, and the percentages of each are presented in Table 1 . For this purpose, "Totally agree" and "strongly agree" were categorized into category 1, "agree" and "slightly agree" into category 2, and "Totally disagree; strongly disagree; slightly disagree; neither agree nor disagree" into category 3.

A threshold of 66% for agreement (categories 1 and 2) or disagreement (category 3) was required for each question to reach consensus and a threshold of 80% for strong consensus. The criteria mentioned above are recommended for hospital discharge and termination of contact isolation after COVID-19 infection [20] . However, positive SARS Cov 2 RT-PCR results were reported even 13 days after clinical symptoms mentioned resolved [21] . This may be related to the immune status of each patient, use of glucocorticoids, and time of virus clearance [22] . ESMO recommends restarting treatment after 2 negative RT-PCR tests with a one week interval following clinical [14] . VATS and thoracotomy approaches [25] . Also, there is information from nonrandomized phase I and II studies comparing SBRT with surgery, a conjunct J o u r n a l P r e -p r o o f analysis of these trials showed a better OS at 3 years in patients treated with SBRT [25] . So, SBRT could be considered an option in these patients [26] . If the patient is also candidate of adjuvant RT (R1 or pathological N2), the treatment could be administered after the completion of chemotherapy, or delayed till 3 months after surgery. In a review evaluation of 3500 of the National Cancer

Database, the patients that received sequential chemoradiation had a better survival compared with the group of concomitant chemoradiation [27] [28] [29] .

Recommendation: Hypofractionated radiotherapy is not recommended in this clinical scenario.

Although hypofractioning is gaining acceptance, high technology is necessary in order to implement this modality. The dose should be 50-60Gy in 25-30 fractions [30, 31] .

Recommendation: Every patient should be considered for chemoradiation

The standard treatment is chemoradiation followed by durvalumab in patients who did not progress during the next 42 days. The two-year survival of stage III NSCLC patients ranges from 24-55% [32] , but increases to 66% with concomitant J o u r n a l P r e -p r o o f chemoradiation followed by durvalumab [33] . Hypofractionation is not recommended concurrently with chemotherapy.

Recommendation: A concurrent approach is preferred, although sequential treatment can be kept in mind for specific cases in which toxicity is considerable.

Concurrent chemoradiation over sequential treatment is superior in terms of OS, but the benefit is modest and the toxicities could be higher, so the risk for immunosuppression in the pandemic could be less for the sequential therapy [34, 35] . The choice of treatment should be made based on clinical features like patients´ symptoms, rate of disease progression, disease burden, (i.e. patients with hilar tumors or vascular compression) could be treated with RT [36] . No hypofractionation or only mild hypofractionation (i.e. 50Gy in 20Fx) is recommended. While this modality could prolong the treatment duration it can delay the time to chemoradiation with the expected immunosuppressive effects and daily visits.

Recommendation: G-CSF should not be routinely used, only if neutropenia develops and represents an issue.

In this scenario the use of G-CSF is associated with a higher probability of toxicity when administered during chemoradiation, however, a review readdressed this question for the safety of this combination [40] .

Recommendation: Hypofractionated schedules in this clinical setting are not currently fully supported by available evidence. Nonetheless, the approach could be an option for treatment in some patients that have access to the technology.

Shorter courses of RT are associated with less immunosuppression in other cancers, though currently evidence for lung cancer in this clinical setting is scarce and therefore, an evidence-based recommendation cannot be made [40] . This approach could, however, diminish the risk of infection by minimizing the number of visits to the hospital to receive treatment [38, 39] . Nonetheless, hypofractionated schedules increase risk of radiation pneumonitis and should be decided in case by case scenario [41] . In many retrospective cohorts, delays on treatment have an impact on prognosis, especially in earlier stages [42] . Similarly, in advanced disease, shorter delays were correlated with poorer outcomes. The association reflects the biology of the disease, as symptomatic patients often receive expedited treatment to control symptoms [43, 44] . Considering the highly effective therapies available in the firstline setting with a clear impact in OS, PFS, and ORR its necessary to make a counterbalance considering risk and benefits [45] . Patients that have oligometastatic disease with low disease burden may be suitable for an aggressive approach (surgery or radiotherapy, ablative techniques) to all metastatic lesions looking for a curative intention strategy [46] . Docetaxel has a modest ORR benefit compared with best supportive care (less than 10%) and a median PFS of 2-3 months. Meanwhile, pemetrexed has demonstrated similar efficacy but a more favorable toxicity profile [45] . Considering Though this has not been evaluated in this particular scenario, many studies have shown evidence regarding the use of the serum level of CEA as a prognostic and predictive factor for recurrence and death [47] [48] [49] . Guidelines do not recommend determination of serum CEA, however, considering potential delays in response evaluation during this pandemic, it could provide valid information. [49] 10.0 Non oncogene-driver mutations and suitable for immunotherapy

immunotherapy be considered a safe treatment during the pandemic?

Recommendation: Immunotherapy should be administered to all candidate patients. Until now, no evidence of an increased mortality has been documented, and a recent study shows PD-1 blockade in lung cancer is not associated with increased severity of COVID-19.

Theoretically patients under immunotherapy could be more immunocompetent than non-users, thus potentially a greater inflammatory response could be established.

Cytokine release syndrome (CRS) is a rare complication seen with car-T cells therapy or PD-1 inhibitors characterized by an increased level of IL-6 and IFNγ [50] . The acute respiratory distress syndrome (ARDS) is one of the most lethal complications in almost one third of patients in this pandemic, due to a secondary cytokine storm that produce a hyperactivation of T-cells that contribute to the J o u r n a l P r e -p r o o f severe immune injury. This proinflammatory state in the COVID-19 patients could progress to an acute inflammatory distress syndrome ARDS or even to multiorgan failure [51, 52] . Nonetheless, current evidence suggests that PD-1 blockade does not impact the severity of COVID-19 in patients with lung cancer [53] . Recently in a model-based approach pembrolizumab 400mg 6-weekly 6W was compared with 3-weekly 3W approved regimens in terms of pharmacokinetic and security. The 6W regimen had similar predicted exposure, likewise, fewer than 1% of patients had transiently lower concentrations compared to 3W regimens, nonpeak concentrations over the security dose of 10mg/kg [54] . Nivolumab 480mg 4W

regimen is recommended too based in a success pharmacokinetic (PK) analyses comparing with 3mg/kg and flat dose of 240mg 2W [55] . In addition, durvalumab 1500mg 4-weekly regimen has been explored in the CASPIAN trial in extensive SCLC [37] and it is being tested in the ongoing PACIFIC (2,4,5 and 6) trials [56] with an acceptable safety. Additionally, atezolizumab can be administered 1680 q4w, a dosing regimen that has been shown to be interchangeable with 1200 q3w, but offers patients longer visit intervals [57] . All the regimens are FDA approved.

Recommendation: Patients on TKIs should be monitored for pulmonary symptoms in every visit or telephone call, but patients suitable to receive TKIs must do so.

One concern is the increased risk of pneumonitis in patients with NSCLC during TKIs treatment. Based on a recent metanalysis the overall incidence of EGFR-TKI pneumonitis was 1.12% in patients without prior exposure to EGFR-TKI, and 1.13% in EGFR-TKI retreatment group. Grade ≥3 pneumonitis was presented in 0.81% of patients in the total cohort [58] . Likewise, all grade and grade ≥3 pneumonitis were reported in 2.14% and 1.55% respectively, of patients with an ALK inhibitors [59] . Further, data from the ALK in Lung Cancer Trial of Brigatinib in 1st Line (ALTA-1L) showed patients treated with brigatinib and crizotinib presented with G3/4 interstitial lung disease or pneumonitis in 3% and 0.7% of cases, respectively [60] . Chemotherapy has shown to prolong OS in patients with PS2. Also, a metanalysis confirmed the benefit of platinum-based regimens compared with monotherapy in this population, at the cost of an increase in hematologic toxicity, more grade 3-4

anemia and neutropenia [65, 66] . Regarding platinum therapy, superiority of carboplatin-based combination over monotherapy has been reported in two large J o u r n a l P r e -p r o o f phase III trials with an acceptable toxicity profile [67, 68] . Therefore, platinumpreferably carboplatin doublets could be considered in eligible PS 2 patients, but during this pandemic the risk of contracting the infection should be considered. TKIs demonstrated in many phases 3 trials a more favorable toxicity profile compared with chemotherapy. Additionally, they help achieve longer responses.

On the other hand, treatment beyond progression in slow progressive disease could be employed as a valid strategy. Considering risks during pandemic, longer monitorization of these patients could be considered an option, preferable with intermediate evaluation with telemedicine or phone calls as back-up resources.

regimens with immunotherapy treatment could be followed with 4-weekly outpatient visits rather than 3-weekly?

Recommendations: Patients on chemotherapy or combination treatments with immunotherapy could be monitored with 4-weekly outpatient visits. it is not recommended to delay the studies in these patients. However, once a patient has been diagnosed to have extensive stage disease, further standing is not required, except for brain imaging [74] .

Recommendation: If surgery times are prolonged, chemotherapy or SBRT can be used instead.

Only 5% of patients present in early stages are candidates for surgical treatment, and the decision to carry out surgery should be discussed by a multidisciplinary team, since a complete evaluation of the mediastinum is required, this in addition 

Recommendation: The omission/delay of chemotherapy treatment is not recommended due to the high rate of growth.

Due to the high rate of tumor growth that occurs in the SCLC and that it is considered a systemic disease from the start, the omission/delay of standard chemotherapy treatment is not recommended in these patients [77] .

Recommendation: Delaying the starting time of RT treatment is not recommended due to the high rate of growth; moreover, early initiation has a benefit in survival.

The use of concurrent chemotherapy with radiotherapy is the standard of treatment for patients with limited disease due to the impact on survival. In patients with limited disease, the use of etoposide and cisplatin with radiotherapy has response rates of 70% to 90% with a 5-year survival of 25% to 30%. Use of concurrent vs. sequential therapy has been questioned [76] , but several studies, including a

Cochrane study, have shown benefit for the early start of RT [78] . Therefore, if J o u r n a l P r e -p r o o f possible, early radiation initiation is recommended, but If toxicity is an important issue a sequential approach could be an option.

Recommendation: Considering the current situation, the best option is to delay the administration of radiotherapy until 6 months after the start of the adjuvant treatment without having a significant impact on oncological outcomes.

SCLC patients are a high-risk population for developing brain metastases, which are associated with poor survival. As such, it is not recommended to suspend the administration of PCI in these patients. One could, however, consider delaying the administration of the therapy until 6 months after the start of the adjuvant without significantly impacting on the outcomes.

PCI has been shown to be effective in a meta-analysis of seven randomized studies that included 978 patients. It showed a reduction in the incidence of metastases (relative risk [RR] 0.46; 95% CI 0.38-0.57) and a decrease in mortality (RR 0.84; 95% CI 0.73-0.97).

In the same study, a subgroup analysis showed there was no difference in mortality when starting radiotherapy less than 6 or more than 6 months after starting chemotherapy treatment, there was only a higher risk of developing brain metastases in patients that started PCI later than 6 months [79] . Regular contrastenhanced cranial MRI follow up should be available if PCI is not performed.

Recommendation: Due to lower probability of developing hematological toxicity, cisplatin should be considered.

The substitution of cisplatin for carboplatin could be considered due to its different toxicity profile, however taking into account that the neutropenia rate is increased,

and that the current evidence shows that the use of granulocyte colony stimulating factor in conjunction with chemotherapy and radiotherapy increases the toxicity. In 

Recommendation: PCI can be omitted because of the controversial benefit in survival.

In extensive disease the benefit of prophylactic radiotherapy to the brain is controversial due to discordant results. In addition to the current systemic treatment, the recommendation is that it could be omitted to decrease the risks of the patients by offering follow-up only.

In 

Malignant Pleural Mesothelioma (MPM) is a relatively low-frequency tumor, nonetheless worldwide incidence has been rising during the last decade, and it is likely that this trend will continue. The exposure to asbestos is accountable for approximately 80% of MPM cases [87] . Following this pattern, several large-scale epidemiological analyses predicts that incidence in Europe and Latin America will reach its highest historic level in 2020 [88] . Screening for mesothelioma in high risk population has been studied and is not recommended based on the absence of benefit in mortality. Patients with mesothelioma often present with high symptoms burden that require attention promptly, even in early stages. Considering the limited access to surgery and hospitalization risks, neoadjuvant treatment could be preferred over adjuvant approaches during the pandemic. Extrapleural pneumonectomy is associated with increased mortality and morbidity, despite this, it is a valid procedure considering pandemic situation, total pleurectomy is considered safer [90, 91] .

Recommendation: We currently do recommend trimodal treatment, including radiotherapy. This is a fast-progressing tumor which is radiosensitive and therefore OS benefit could be achieved with trimodal therapy.

The efficacy of trimodal treatment using chemotherapy surgery and hemithoracic radiotherapy has been explored in some retrospective analyses and phase 2 trials in patients who complete the treatment has been reported [92] [93] [94] [95] [96] . However, an important increased risk of developing pneumonitis up to 30% has to be assumed [97] .

Recommendation: Patients could be considered for deferring cytotoxic therapy if they are asymptomatic and have a low burden of disease.

Some guidelines recommend deferring treatment in asymptomatic patients with good functional status with unresectable disease, considering starting treatment after clinical or radiographical progression. This could be a good option for selected patients that could be tracked to identify symptoms of progression during pandemic [89] .

Recommendation: Consider starting first-line treatment in every symptomatic patient preferably with a carboplatin-based regimen in combination with pemetrexed.

Comparison data has emerged between cisplatin versus carboplatin regimens combined with pemetrexed in medically inoperable population. Oncological outcomes in a cohort of more than 1,700 patients were similar [96] . Guidelines recommend carboplatin-based regimen even in patients with good functional status J o u r n a l P r e -p r o o f PS 0-1. Options for patients who are not candidates for platinum could be monotherapy regimens with pemetrexed or vinorelbine with poorer outcomes [98, 99] .

Recommendation: Due to the lack of efficacy in the available data, pemetrexed maintenance therapy is not be recommended. Regarding bevacizumab, we do not consider the benefit could outweigh the risks of COVID-19 infection.

Two trials, and one phase 3 trial have demonstrated an OS benefit with bevacizumab both during the induction phase and as maintenance. Remarkably, the median OS benefit does not exceed the 3 months, at the cost of increased grade 3-4 adverse events [100] . Additionally, considering the extra visits, omitting maintenance during the pandemic is advised [101] . The efficacy of pemetrexed maintenance therapy is not well stablished and should not be recommended as well.

Recommendation: Second-line treatment in asymptomatic patients could be delayed until clinical or radiological progression, considering risks during the pandemic.

Limited data are available to guide second-line treatment and beyond. Prognosis in patients who progress is ominous, and a standard of care is not available. Limited evidence from phase II trials have identified subgroups of patients who will benefit J o u r n a l P r e -p r o o f from receiving subsequent therapy. In the other hand checkpoint inhibitors therapy is emerging in this scenario and could be used for symptomatic patients, independently of PDL1-expression. A monotherapy strategy with pembrolizumab [102] [103] [104] or nivolumab [105] could represent safer options when compared with the combined treatment with nivolumab and ipilimumab [106, 107] .

In the midst of the COVID-19 pandemic, oncologists will need to weigh the risks of death and morbidity from COVID-19 against the magnitude of benefit of intended cancer therapies. Early estimates from China suggest an overall case fatality rate of 2%, increasing to 8% for 70-79 year-olds, and 15% for those ≥80 years of age [108] . Case fatality rates (CFR) are also markedly higher among patients with comorbidities, 11% for cardiovascular disease, 7% for diabetes and 6% for chronic respiratory disease. Patients with cancer are among those most vulnerable to severe illness from respiratory viral infections [109] . have not yet been strongly affected by this pandemic.

There is scarce information about the potential consequences of modifications to the standard of care. Additionally, until now, the impact, timeline, and duration of pandemic remain unknown; consequently, the uncertainty for cancer patients regarding their treatment will last longer. However, with this pandemic having reached all areas across the globe, there is an increasing need for guidance for all oncologists to optimize resources, until this current crisis is over. With some luck, in the short future, we will recover the certainty and security to treat cancer patients using the established standard of care. Dr. Oscar Arrieta reports personal fees from Pfizer, grants and personal fees from Astra zeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Lilly, personal fees from Merck, personal fees from Bristol Myers Squibb, grants and personal fees from Roche, outside the submitted work. All the remaining authors declare no conflict of interest. J o u r n a l P r e -p r o o f

Centro de Investigación y Manejo del Cáncer (CIMCA)

Hospital Vivián Pellas

Coordinador de la sección Oncología

Centro Oncológico Riojano Integral

Hospital de Rehabilitacion Respiratoria María Ferrer

Unidad Oncológica Molecular Peruana

Thoracic Oncology Program Memorial Cancer Institute, Memorial Healthcare System

Centro Integral Oncología Clara Campal Bacelona

Clínica Colsanitas

Speaker: MSD, Roche, Astra Zeneca, BMS, Novartis. Advisory and Consulting: MSD

Viteri reports personal fees and non-financial support from Roche, personal fees from BMS, non-financial support from OSEPharma, personal fees from MSD, non-financial support from Merck Serono outside the submitted work

Reports personal fees from AstraZeneca

Principal Investigator: BMS

Consulting or Advisory Role, Company: AstraZeneca; Travel, Accommodations, Expenses Company: Mundipharma, Boehringer Ingelheim, Astra Zeneca Dr. Luis Mas: speaker

Bristol-Myers Squibb and The Foundation for Clinical and Applied Cancer Research -FICMAC., other from Pfizer

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The incidence of ALK inhibitor-related pneumonitis in advanced non-smallcell lung cancer patients: A systematic review and meta-analysis. Lung Cancer

Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer

First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer: The ASPIRATION Study

Epidermal growth factor receptor tyrosine kinase inhibitors beyond progressive disease: a retrospective analysis for Japanese patients with activating EGFR mutations

Continued treatment with gefitinib beyond progressive disease benefits patients with activating EGFR mutations. Lung Cancer

Systemic Treatment Options for Brain Metastases from Non-Small-Cell Lung Cancer

What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis

Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel

Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised

Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2

Phase II trial of single-agent oral vinorelbine in elderly (> or =70 years) patients with advanced non-small-cell lung cancer and poor performance status

Metronomic oral vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer: results of a phase II trial (MOVE trial)

Telemedicine for cancer patients during COVID-19 pandemic: between threats and opportunities

Hyperprogressive Disease in Patients With Advanced Non-Small Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy

Immune-related adverse events with immune checkpoint inhibitors in thoracic malignancies: focusing on non-small cell lung cancer patients

Characteristics and outcomes of small cell lung cancer patients diagnosed during two lung cancer computed tomographic screening programs in heavy smokers

American College of Chest Physicians evidence-based clinical practice guidelines

A Meta-Analysis of Thoracic Radiotherapy for Small-Cell Lung Cancer

Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer

Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer

Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission

Carboplatin-or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data

First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

Role of thoracic consolidation radiation in extensive stage small cell lung cancer: A systematic review and meta-analysis of randomised controlled trials

Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial

Prophylactic Cranial Irradiation in Extensive Small-Cell Lung Cancer

Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial

A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer

Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline

A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study

Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma

Trimodality Treatment of Malignant Pleural Mesothelioma: An Institutional Review

Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy

Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma

Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program

Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma

Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial

Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma

Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial

Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma

Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, openlabel, phase 1b trial

03 Long-Term Overall Survival for Patients with Malignant Pleural Mesothelioma on&#xa0;Pembrolizumab Enrolled in KEYNOTE-028

Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma

Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma

Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial

Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention

Respiratory Viral Infections in Patients With Cancer or Undergoing Hematopoietic Cell Transplant

Cancer is associated with severity and mortality of patients with COVID-19 a systematic review and meta-analysis

Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 -COVID-NET, 14 States

Treatment guidance for lung cancer patients during the COVID-19 pandemic

localized (I-IIIA) mesothelioma? Patients with localized diseased must be discussed in a multidisciplinary session aimed for curative intent, considering neoadjuvant chemotherapy followed by surgery (preferably total pleurectomy/decortication).

Do you have any consideration for trimodality (chT, surgery & RT) treatment? We currently do recommend trimodal treatment, including radiotherapy. This is a fast-progressing tumor which is radiosensitive and therefore OS benefit could be achieved with trimodal therapy.