Crystal structure and Hirshfeld surface analysis of cyclo-tetra-bromido-1κ2Br,3κ2Br-tetra-kis-(µ2-2-{[(pyridin-2-yl)meth-yl]amino}-ethane-1-thiol-ato-κ3N,S:S)tetra-mercury(II).

The macrometallacyclic title compound, [Hg4Br4(C8H11N2S)4] or [((HgL 2)(HgBr2))2] (1) where HL = 2-{[(pyridin-2-yl)meth-yl]amino}-ethane-1-thiol, was prepared and structurally characterized. The Hg2+ complex crystallizes in the P21/c space group. The centrosymmetric Hg4S4 metallacycle is constructed from metal ions with alternating distorted tetra-hedral Br2S2 and distorted seesaw N2S2 primary coordination environments with pendant pyridyl groups. The backfolded extended chair metallacycle conformation suggests inter-actions between each of the bis-chelated mercury atoms and Br atoms lying above and below the central Hg2S4 plane. Supra-molecular inter-actions in 1 include a fourfold aryl embrace and potential hydrogen bonds with bromine as the acceptor. Hirshfeld surface analysis indicates that H⋯H (51.7%), Br⋯H/H⋯Br (23.0%) and C⋯H/H⋯C (9.5%) inter-actions are dominant.

Achieving international biodiversity targets: Learning from local norms, values and actions regarding migratory waterfowl management in Kazakhstan.

Migratory species are protected under international legislation; their seasonal movements across international borders may therefore present opportunities for understanding how global conservation policies translate to local-level actions across different socio-ecological contexts. Moreover, local-level management of migratory species can reveal how culture and governance affects progress towards achieving global targets. Here, we investigate potential misalignment in the two-way relationship between global-level conservation policies (i.e. hunting bans and quotas) and local-level norms, values and actions (i.e. legal and illegal hunting) in the context of waterfowl hunting in northern Kazakhstan as a case-study.Northern Kazakhstan is globally important for waterfowl and a key staging area for arctic-breeding species. Hunting is managed through licences, quotas and seasonal bans under UN-AEWA intergovernmental agreements. To better understand the local socio-ecological context of waterfowl hunting, we take a mixed-methods approach using socio-ecological surveys, informal discussions and population modelling of a focal migratory goose species to: (a) investigate motivations for hunting in relation to socio-economic factors; (b) assess knowledge of species' protection status; and (c) predict the population size of Lesser White-fronted Geese (LWfG; Anser erythropus; IUCN Vulnerable) under different scenarios of survival rates and hunting offtake, to understand how goose population demographics interact with the local socio-ecological context.Model results showed no evidence that waterfowl hunting is motivated by financial gain; social and cultural importance were stronger factors. The majority of hunters are knowledgeable about species' protection status; however, 11% did not know LWfG are protected, highlighting a key area for increased stakeholder engagement.Simulations of LWfG population growth over a 20-year period showed LWfG are highly vulnerable to hunting pressure even when survival rates are high. This potential impact of hunting highlights the need for effective regulation along the entire flyway; our survey results show that hunters were generally compliant with newly introduced hunting regulations, showing that effective regulation is possible on a local level. Synthesis and applications. Here, we investigate how global conservation policy and local norms interact to affect the management of a threatened migratory species, which is particularly important for the protection and sustainable management of wildlife that crosses international borders where local contexts may differ. Our study highlights that to be effective and sustainable in the long-term, global conservation policies must fully integrate local socio-economic, cultural, governance and environmental contexts, to ensure interventions are equitable across entire species' ranges. This approach is relevant and adaptable for different contexts involving the conservation of wide-ranging and migratory species, including the 255 migratory waterfowl covered by UN-AEWA (United Nations Agreement on the Conservation of African-Eurasian Migratory Waterbirds).

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus

Aim To stablish a consensus on the treatment strategy for advanced non–small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. Methods After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1–9 range scale (1–3 = disagree, 7–9 = agree). Consensus was reached if 2/3 of the participants are in the median range. Results In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. Conclusions A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations (AU)

Gender influence on work satisfaction and leadership for medical oncologists: a survey of the Spanish Society of Medical Oncology (SEOM).

BACKGROUND: Women represent an increasing proportion of the oncology workforce; however, globally this does not translate into leadership roles, reflecting disparities in career opportunities between men and women. The Spanish Society of Medical Oncology (SEOM) undertook a survey to investigate gender disparity in the Spanish oncology context. DESIGN: An online survey was made available to SEOM medical oncologists between February and May 2019. It included demographics, professional context and achievements, parenthood and family conciliation issues, workplace gender bias, and approaches to address disparities. RESULTS: Of the 316 eligible respondents, 71.5% were women, 59.5% were aged 45 or younger, and 66.1% had children. Among women, 12.4% were division or unit heads, compared with 45.5% of men, with most women (74.3%) being attending medical oncologists, compared with 45.5% of men. More males were professors (34.4% versus 14.2% of females), had a PhD (46.7% versus 28.8%), and/or had led clinical research groups (41.1% versus 9.7%). Spending time overseas after completing a residency was also more common for men than women (34.4% versus 20.4%). Professional satisfaction was similar between genders, driven primarily by patient care and intellectual stimulation. More women (40.7%) considered parenthood to have a strong negative impact on their career, compared with men (9.0%). Main perceived barriers to gender equality included a lack of work-life balance (72.6% women, 44.4% men), bias of peers and superiors (50.0% women, 18.9% men), and different career goals (41.2% women, 24.4% men). Preferred solutions included educational programs and scholarships (52.9%), communication and leadership training (35.8%), childcare at conferences (33.2%), and postmaternity return-to-work incentives (32.0%). CONCLUSION: There is a clear paucity of equal opportunities for female oncologists in Spain. This can be addressed by encouraging professional development and merit recognition particularly for younger female oncologists, and empowering women to be involved in management and leadership of institutions and professional societies.

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus.

AIM: To stablish a consensus on the treatment strategy for advanced non-small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. METHODS: After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1-9 range scale (1-3 = disagree, 7-9 = agree). Consensus was reached if 2/3 of the participants are in the median range. RESULTS: In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. CONCLUSIONS: A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations.

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019).

Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus.

PURPOSE: Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally advanced disease. Uncertainty on how to treat patients at disease progression prompted us to develop a consensus document on post-immunotherapy options in Spain for patients with advanced wild-type lung adenocarcinoma. METHODS: After extensive literature review, a 5-member scientific committee generated 33 statements in 4 domains: general aspects (n = 4); post-durvalumab in locally advanced disease (n = 6); post-first-line immunotherapy ± chemotherapy in advanced/metastatic disease (n = 11); and post-first-line platinum-based chemotherapy in advanced/metastatic disease (n = 12). A panel of 26 lung cancer experts completed 2 Delphi iterations through an online platform rating their degree of agreement/disagreement (first-round scale 1-5 and second-round scale 1-4, 1 = strongly disagree, 4/5 = strongly agree) for each statement. Second-round consensus: ≥ 70% of responses were in categories 1/2 (disagreement) or 3/4 (agreement). RESULTS: Consensus was reached for 2/33 statements in the first Delphi round and in 29/31 statements in the second round. Important variables informing treatment at disease progression with an immunotherapy-based treatment include: disease aggressiveness, previous treatment, accumulated toxicity, progression-free interval, PD-L1 expression, and tumour mutational burden. A platinum-based chemotherapy should follow a first-line immunotherapy treatment without chemotherapy. Treatment with docetaxel + nintedanib may be appropriate post-durvalumab in refractory patients or following progression to first-line chemotherapy + immunotherapy, or second-line chemotherapy after first-line immunotherapy, or first-line chemotherapy in some patients with low/negative PD-L1 expression, or second-line immunotherapy after first-line chemotherapy. CONCLUSIONS: To support decision making following progression to immunotherapy-based treatment in patients with advanced wild-type lung adenocarcinoma, a consensus document has been developed.

Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

In 2011 the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) started a joint project to establish guidelines on biomarker testing in patients with advanced non-small-cell lung cancer (NSCLC) based on current evidence. As this field is constantly evolving, these guidelines have been updated, previously in 2012 and 2015 and now in 2019. Current evidence suggests that the mandatory tests to conduct in all patients with advanced NSCLC are for EGFR and BRAF mutations, ALK and ROS1 rearrangements and PD-L1 expression. The growing need to study other emerging biomarkers has promoted the routine use of massive sequencing (next-generation sequencing, NGS). The coordination of every professional involved and the prioritisation of the most suitable tests and technologies for each case remains a challenge.

Who knows best? Understanding the use of research-based knowledge in conservation conflicts.

The way in which research-based knowledge is used, interpreted and communicated by different actors can influence the dynamics of conservation conflicts. The conflict that occurs between grouse shooting interests and the conservation of birds of prey in Scotland is notoriously complex, involving multiple actors at multiple levels, and shaped by the values and world views of these actors. This paper explores how research-based knowledge is used in the debate by six key organisations, and looks to understand the drivers that may influence knowledge use and interpretation in this, and other, cases of conservation conflict. Research was used to both legitimise and reinforce certain world views, and to support associated political actions that would cause these to become reality. Actors offered divergent interpretations of the same piece of research, emphasising different findings and outcomes. Research-based knowledge was thus employed by actors to support or counter the 'status quo', and challenge other claims that clashed with their own values. Although the intention of such knowledge use is unclear, the selective reconstruction of research by actors could stem from, and reiterate, divergent value systems. This may pose significant challenges to conflict mitigation efforts; whilst some may look to research-based knowledge as the bringer of truth, its interpretation by different actors may exacerbate existing rifts between stakeholders; promoting polarisation of views. Mitigation strategies should be sensitive to this, and aim to improve the inclusiveness and transparency of the knowledge transfer process.

Clinical utility of plasma-based digital next-generation sequencing in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping.

BACKGROUND: Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping. PATIENTS AND METHODS: We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a hybrid-capture-based 73-gene panel. Variants were deemed actionable if they were part of the OncoKB precision oncology knowledge database and classified in four levels of actionability based on their clinical or preclinical evidence for drug response. RESULTS: Eighty-three out of 93 patients (89%) had detectable levels of ctDNA. Potentially actionable level 1-4 genomic alterations were detected in 53 cases (57%), of which 13 (14%) had level 1-2A alterations (Food and Drug Administration-approved and standard-care biomarkers according to lung cancer guidelines). Frequencies of each genomic alteration in ctDNA were consistent with those observed in unselected pulmonary adenocarcinomas. The majority of the patients (62%), particularly those with actionable alterations (87%), had more than one pathogenic variant in ctDNA. The median turnaround time to genomic results was 13 days. Twelve patients (13%) received genotype-matched therapies based on ctDNA results, deriving the expected clinical benefit. Patients with co-occurring pathogenic alterations had a significantly shorter median overall survival as compared with patients without co-occurring pathogenic alteration (multivariate hazard ratio = 5.35, P = 0.01). CONCLUSION: Digital NGS of ctDNA in lung cancers with insufficient tumor samples for tissue sequencing detects actionable variants that frequently co-occur with other potentially clinically relevant genomic alterations, allowing timely initiation of genotype-matched therapies.

Efficacy of tyrosine kinase inhibitors in EGFR-mutant lung cancer women in a real-world setting: the WORLD07 database

Background. The WORLD07 project is a female specific database to assess the characteristics of women with lung cancer. Methods. WORLD07 database sets up in 2007, and prospectively stores clinical characteristics, treatment, outcome, and follow-up of lung cancer women. All women with epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) were selected for this analysis. Results. From October 2007 to December 2012, a total of 1775 NSCLC women were recruited. EGFR mutation was identified in 34.4% of patients. Upfront EGFR tyrosine kinase inhibitor (TKI) reported a response rate of 60%, a median progression-free survival of 11.7 months, and median overall survival of 23.0 months. EGFR TKI, EGFR-mutation type, and smoking status did not impact in the outcome of treated women. Conclusion. Prevalence of EGFR mutation in women with NSCLC is higher than overall population with NSCLC. Efficacy of EGFR TKI in this real-world setting is similar to that previously reported (AU)

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Efficacy of tyrosine kinase inhibitors in EGFR-mutant lung cancer women in a real-world setting: the WORLD07 database.

BACKGROUND: The WORLD07 project is a female specific database to assess the characteristics of women with lung cancer. METHODS: WORLD07 database sets up in 2007, and prospectively stores clinical characteristics, treatment, outcome, and follow-up of lung cancer women. All women with epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) were selected for this analysis. RESULTS: From October 2007 to December 2012, a total of 1775 NSCLC women were recruited. EGFR mutation was identified in 34.4% of patients. Upfront EGFR tyrosine kinase inhibitor (TKI) reported a response rate of 60%, a median progression-free survival of 11.7 months, and median overall survival of 23.0 months. EGFR TKI, EGFR-mutation type, and smoking status did not impact in the outcome of treated women. CONCLUSION: Prevalence of EGFR mutation in women with NSCLC is higher than overall population with NSCLC. Efficacy of EGFR TKI in this real-world setting is similar to that previously reported.

A consensus statement on the gender perspective in lung cancer

Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women (AU)

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Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy

Background/Aim. First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. Patients and methods. This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. Results. Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. Conclusion. Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors (AU)

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Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

BACKGROUND/AIM: First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. PATIENTS AND METHODS: This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. RESULTS: Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. CONCLUSION: Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

A consensus statement on the gender perspective in lung cancer.

Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.

SEOM Clinical Guideline for bone metastases from solid tumours (2016)

Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone (AU)

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SEOM Clinical Guideline for bone metastases from solid tumours (2016).

Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.

Recomendaciones para el diagnóstico radiológico y la valoración de la respuesta terapéutica en el cáncer de pulmón. Consenso nacional de la Sociedad Española de Radiología Médica y la Sociedad Española de Oncología Médica / Recommendations for radiological diagnosis and assessment of treatment response in lung cancer: a national consensus statement by the Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology

En esta última década se han producido avances importantes en el diagnóstico y tratamiento del cáncer de pulmón que han permitido mejorar su pronóstico. Por ello, la Sociedad Española de Radiología Médica (SERAM) y la Sociedad Española de Oncología Médica (SEOM) han elaborado un documento de consenso nacional para hacer recomendaciones sobre el diagnóstico radiológico y la valoración de la respuesta terapéutica en pacientes con cáncer de pulmón. Este grupo de expertos recomienda la tomografía computarizada multidetector (TCMD) como la técnica de elección para estudiar esta enfermedad, y respecto al informe radiológico incluir una valoración completa siguiendo el sistema de estadificación TNM. Por último, cuando el paciente reciba inmunoterapia, además de usar los criterios para evaluar la respuesta en tumores sólidos (Response Evaluation Criteria in Solid Tumors [RECIST 1.1]) también habrá que usar los criterios de respuesta inmunológica (Immune-Related Response Criteria [irRC]) (AU)

The last decade has seen substantial progress in the diagnostic and therapeutic approach to lung cancer, thus meaning that its prognosis has improved. The Spanish Society of Medical Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM) have therefore produced a national consensus statement in order to make recommendations for radiological diagnosis and assessment of treatment response in patients with lung cancer. This expert group recommends multi-detector computed tomography (MDCT) as the technique of choice for investigating this disease. The radiology report should include a full assessment by the TNM staging system. Lastly, when the patient is on immunotherapy, response evaluation should employ not only Response Evaluation Criteria in Solid Tumours (RECIST 1.1) but also Immune-Related Response Criteria (irRC) (AU)