Diagnosis Of Advanced Lung Cancer Research Articles

Comparison of 68Ga-FAP-2286 and 18F-FDG PET/CT in the diagnosis of advanced lung cancer.

The 68Ga/177Lu-FAP-2286 is a newly developed tumor imaging agent that shows potential for visualizing and treating tumor stroma. The objective of this research was to evaluate the effectiveness of 68Ga-FAP-2286 PET/CT and 18F-FDG PET/CT in diagnosing advanced lung cancer. In this prospective study, patients with lung cancer who underwent 68Ga-FAP-2286 and 18F-FDG PET/CT examinations between September 2022 and June 2023 were analyzed. Lesion uptake was converted to SUVmax. A paired T-test was used to compare the SUVmax, and the number of positive lesions detected by the two methods was recorded. In total, 31 participants (median age: 56 years) were assessed. The uptake of 68Ga-FAP-2286 was significantly higher than that of 18F-FDG in primary lesions (9.90 ± 5.61 vs. 6.09 ± 2.84, respectively, P < 0.001), lymph nodes (7.95 ± 2.75 vs. 5.55 ± 1.59, respectively, P=0.01), and bone metastases (7.74 ± 3.72 vs. 5.66 ± 3.55, respectively, P=0.04). Furthermore, the detection sensitivity of lymph nodes using 68Ga-FAP-2286 PET/CT was superior to that with 18F-FDG PET/CT [100% (137/137) vs. 78.8% (108/137), respectively], as well as for bone metastases [100% (384/384) vs. 68.5% (263/384), respectively]. However, the detection sensitivity for primary tumors using both modalities was comparable [100% (13/13) for both]. Compared to 18F-FDG PET/CT, 68Ga-FAP-2286 PET/CT demonstrated better lesion detection capabilities for lung cancer, particularly in lymph nodes and bone metastases, providing compelling imaging evidence for the efficacy of 177Lu-FAP-2286 treatment.

Regional trends in diagnosis of advanced lung cancer in Michigan over 33 years.

Lung cancer is the most common cancer killer worldwide. Nearly 80 percent of lung cancers are diagnosed at advanced stages. Lack of access to medical care and undwerutilized lung cancer screening are key reasons for advanced diagnoses. We sought to understand the regional differences in presentation of lung cancer across Michigan. Utilizing a comprehensive cancer registry over 33 years, our goal was to examine associations between sociodemographic patient factors and diagnoses at advanced stages. The Michigan Cancer Registry was queried from 1985 to 2018 to include all new diagnoses of non-small cell lung cancer (NSCLC) using International Classification of Diseases for Oncology (ICD-O) version 3 codes. NSCLC was categorized as early, regional and distant disease. Advanced disease was considered to be any disease that was regional or distant. NSCLC rates were calculated and mapped at the zip code level using the 2010 population as the denominator and spatial empirical Bayes methodology. Regional hospital service areas were constructed using travel time to treatment from the patient's zip code centroid. Logistic regression models were estimated to investigate the significance of rural vs. urban and travel time on level of disease at presentation. Kaplan-Meier and multivariate survival analysis was performed to evaluate the association between distance from the nearest medical center and length of survival controlling for known risk factors for lung cancer. From 1985 to 2018, there were 141,977 patients in Michigan diagnosed with NSCLC. In 1985, men were 2.2 times more likely than women to be diagnosed but by 2018 women and men developed disease at equal rates. Mean age was 67.8 years. Among all patients with known stage of disease, 72.5% of patients were diagnosed with advanced disease. Regional and distant NSCLC rates were both higher in the northern parts of the state. Longer drive times in rural regions also significantly increased the likelihood of advanced NSCLC diagnoses, in particular regional lung cancer. Patients with longer drive times also experienced overall worse survival after controlling for other factors. Regional disparities exist in Michigan for diagnoses of NSCLC at advanced stages. Factors such as lack of screening in urban regions and distances to treating institutions in rural areas likely contribute to the increased likelihood of advanced NSCLC. Future interventions should target the specific needs of residents to detect disease at earlier stages and improve overall outcomes.

Role of the clinical nurse specialist as a non-medical prescriber in managing the palliative care needs of individuals with advanced lung cancer.

Rapid identification of the palliative care needs of individuals with a diagnosis of advanced lung cancer is crucial to maximise the patient's quality of life by upholding exemplary standards of patient-centred holistic care. The clinical nurse specialist is in an ideal position to contribute to the identification and management of the palliative care needs of individuals with advanced lung cancer through the assessment and timely prescribing of medications to manage distressing symptoms. This paper reviews and critiques the role of the clinical nurse specialist as an independent non-medical prescriber in the management of palliative symptoms in end-of-life care for patients with advanced lung cancer. Published literature highlights the positive impact the clinical nurse specialist has as a non-medical prescriber in addressing the palliative needs of individuals with lung cancer. However, there are barriers and challenges, and to overcome these, maximising resources and the availability of support is required to ensure the delivery of timely, person-centred care. The clinical nurse specialist as a non-medical prescriber is an evolving role. There are a range of factors that may influence the clinical nurse specialist to confidently and competently undertake this role. These include the perception that there will be an escalation in the workload, concerns about increased accountability and inadequate mentoring for this new role. To incentivise this role, multidisciplinary support is essential in promoting the clinical nurse specialist's confidence for developing this service to individuals with advanced lung cancer.

The association between the coronavirus disease 2019 (COVID-19) pandemic and quality of life and depression symptoms in patients with advanced lung cancer.

12122 Background: It is unclear whether patients with cancer experience greater distress as a result of the COVID-19 pandemic. Thus, we assessed the relationship of the COVID-19 pandemic with quality of life (QOL) and depression symptoms in patients newly diagnosed with advanced lung cancer. Methods: We conducted a cross-sectional study of patients with advanced lung cancer enrolled in two multisite randomized supportive care trials. We enrolled adult patients within 12 weeks of diagnosis of advanced lung cancer and an Eastern Cooperative Oncology Group (ECOG) Performance Status from 0 to 3 across 23 institutions in the United States. At the time of enrollment, participants completed the Functional Assessment of Cancer Therapy-Lung (FACT-L), which includes four wellbeing subscales (i.e., physical, social, emotional, and functional) as well as lung cancer symptoms, and the Patient Health Questionnaire-9 (PHQ-9) to assess their QOL and depression symptoms, respectively. We compared QOL and depression symptoms between participants enrolled prior to COVID-19 (i.e., those enrolled in the following time periods: March 2018 to January 2019 and March 2019 to January 2020) and during the COVID-19 pandemic (March 2020 to January 2021). We used linear regression models adjusting for age, race, gender, and time since diagnosis of advanced cancer to examine the relationship between the period of enrollment and patients’ QOL and depression symptoms. Results: A total of 860 patients were included in this analysis (665 participants enrolled prior to COVID-19 and 195 participants during COVID-19). The two cohorts did not differ significantly with respect to baseline demographic factors [Mean age 65.4 (SD = 11.4), 51.9% female]. In multivariate regression models, enrollment during COVID-19 was not associated with physical (B = -0.16, SE = 0.52, P = 0.763), social (B = -0.48, SE = 0.39, P = 0.217), emotional (B = -0.16, SE = 0.41, P = 0.693), functional (B = -0.83, SE = 0.55, P = 0.128) wellbeing, or lung cancer symptoms (B = -0.11, SE = 0.44, P = 0.806). Enrollment during COVID-19 was not associated with overall QOL (FACT-L: B = -1.32, SE = 1.69, P = 0.436) or depression symptoms (PHQ-9: B = -0.02, SE = 0.45, P = 0.973). Conclusions: Despite the prevailing belief that COVID-19 has negatively impacted QOL and distress in patients with cancer, we found no differences in QOL or depression symptoms in patients newly diagnosed with advanced lung cancer during the COVID-19 pandemic compared to those diagnosed prior to the pandemic. These findings suggest that factors other than the COVID-19 pandemic, such as patients’ experience with their cancer, contribute to their QOL and depression symptoms.

Liquid biopsies to distinguish malignant from benign pulmonary nodules.

Over the past decades, low‐dose computed tomography (LD‐CT) screening has been widely used for the early detection of lung cancer. Increasing numbers of indeterminate pulmonary nodules are now being discovered. However, it remains challenging to distinguish malignant from benign pulmonary nodules, especially those considered to be small or ground‐glass (GGN) nodules. Liquid biopsies have been successfully applied in the diagnosis of advanced lung cancer, and the potential value for early detection of lung cancer has made great progress. Recent studies have demonstrated the value of various blood‐based tumor biomarkers in determining the nature of pulmonary nodules, including cell‐free DNA (cfDNA), microRNAs (miRNAs), circulating tumor cells (CTCs) and tumor‐associated autoantibodies (AAbs). In this review, we summarize the latest progress of liquid biopsies, and their potential applications and challenges in the diagnosis of malignant pulmonary nodules.

Comparison of Differential Diagnosis of Lung Cancer by Diffuse Weighted Imaging and Sagittal Imaging with Short Inversion Recovery Sequence

The differential diagnosis of advanced lung cancer is difficult in clinical practice. Our study aims to compare the value of diffusion weighted imaging (DWI) with short-term inversion recovery sequence (STIR) for sagittal imaging in the differential diagnosis of lung cancer. 149 patients with non-small cell lung carcinoma (NSCLC) were enrolled and underwent DWI and STIR sagittal imaging. To quantify cancer types, we evaluated the apparent diffusion coefficient (ADC) value on DWI and the contrast ratio (CRs) on sagittal imaging. The ADC values of subclasses in NSCLC were significantly higher than small cell lung carcinoma (SCLC) (p &lt;0.01). The mean CRs were 1.59 for SCLC and 1.30 for NSCLC with a significant difference (p &lt; 0.01). Large cell carcinomas (LCC) and adenocarcinomas have significant differences compared to small cell carcinomas (SCC) without difference between squamous cell carcinomas (p &gt; 0.05); this is also the case for CRs. Squamous cell carcinoma and adenocarcinoma have significant differences compared to SCC without difference in LCC (p &gt; 0.05). Qualitative evaluation of the feasible thresholds DWI and STIR showed that the thresholds were 0.9810−3 mm2/s and 1.37 respectively. The specificity and accuracy was 78.5% is 85.3% for DWI, which was significantly higher than STIR (56.3% and 61.0%). The combination of DWI and STIR sequences was superior to DWI alone with an accuracy rate of 94.3%. DWI is more helpful than STIR in differentiating SCLC and NSCLC, and their combined use can significantly improve diagnosis accuracy.

A noninterventional, multinational study to assess PD-L1 expression in cytological and histological lung cancer specimens.

BackgroundThe diagnosis of advanced lung cancer is made with minimally invasive procedures. This often results in the availability of cytological material only for subtype determination and companion diagnostic testing, with the latter being technically and clinically validated on histological material only. Thus, the primary objective of the MO29978 clinical study was to assess programmed death ligand 1 (PD‐L1) protein expression on cytology samples as surrogates for histology samples in patients with lung cancer.MethodsFormalin‐fixed, paraffin‐embedded histological samples and cytological cell blocks from 190 patients were analyzed with immunohistochemical assays using the rabbit monoclonal anti–PD‐L1 antibody clones SP142 and SP263. PD‐L1 expression was quantified on both tumor cells (TC) and tumor‐infiltrating immune cells (IC). Overall concordance, sensitivity, specificity, and accuracy, with a 1% cutoff used for both assays, were assessed for PD‐L1 expression on TC and IC.ResultsIn non–small cell lung cancer histology and cytology samples measured with the PD‐L1 (SP142) antibody (n = 173), the intraclass correlation coefficients were 0.40 and 0.06 on TC and IC, respectively. With SP142 and SP263, accuracies of 74.1% for TC and 51.9% for IC and accuracies of 75.2% for TC and 61.2% for IC, respectively, were reported.ConclusionsOverall, this study has demonstrated that PD‐L1 analysis on TC is feasible in cytological material, but quantification is challenging. Tumor tissue should be preferred over cell block cytology for PD‐L1 immunohistochemical analysis unless laboratories have validated their cytology preanalytical approaches and demonstrated the comparability of histology and cytology for TC PD‐L1 results.

Human Lung Adenocarcinoma-Derived Organoid Models for Drug Screening

SummaryLung cancer is an extremely heterogeneous disease, and its treatment remains one of the most challenging tasks in medicine. Few existing laboratory lung cancer models can faithfully recapitulate the diversity of the disease and predict therapy response. Here, we establish 12 patient-derived organoids from the most common lung cancer subtype, lung adenocarcinoma (LADC). Extensive gene and histopathology profiling show that the tumor organoids retain the histological architectures, genomic landscapes, and gene expression profiles of their parental tumors. Patient-derived lung cancer organoids are amenable for biomarker identification and high-throughput drug screening in vitro. This study should enable the generation of patient-derived lung cancer organoid lines, which can be used to further the understanding of lung cancer pathophysiology and to assess drug response in personalized medicine.

ALK and ROS1 rearrangement tested by ARMS-PCR in non-small-cell lung cancer patients via cytology specimens: The experience of Shanghai Pulmonary Hospital.

Cytology specimens are the main samples used for the diagnosis of advanced lung cancer. The objective of our study was to assess anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 receptor tyrosine kinase (ROS1) genes by an amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) using cytology specimens and to then evaluate the mutation frequency of ALK and ROS1 in non-small-cell lung cancer (NSCLC) patients. A large cohort that consisted of 8180 NSCLC patients who were genetically tested using cytology samples or formalin-fixed and paraffin-embedded (FFPE) samples (tumor tissue or biopsy) from January 2015 to December 2018 were screened. The gene rearrangement ratio and clinical characteristics of the two sample groups were analyzed by SPSS software. In our hospital, cytology specimens are the main resource used for gene testing in NSCLC. In most cases, an abundant quantity of nucleic acid was extracted from the residual liquid-based cell pellet for testing the ALK and ROS1 genes. In certain cases, when the residual cell pellet was insufficient for the gene testing, the cell block and liquid-based cell smear served as alternative options. In addition, we retrospectively analyzed our previous data, and the mutation ratio of the ALK/ROS1 rearrangements obtained by using the cytology samples (4.98%/1.80%) and the FFPE samples (6.06%/1.62%) was almost the same (P-value = .09/.634). This study demonstrated that AMRS-PCR method can effectively identify ALK and ROS1 gene rearrangements and cytology specimens might be an excellent source for routine molecular testing in patients with advanced NSCLC.

Impact of a mature palliative service for patients with lung cancer admitted to the ICU.

102 Background: In 2012 ASCO made the clinical recommendation for patients with stage IV solid organ cancer to receive palliative care consultation (PCC) at the time of detection. This was intended to increase utilization and effectiveness of palliative care. In this study, we estimate the proportion and impact of late "brink of death" PCC for patients with stage III-IV lung cancer admitted to the ICU of a hospital with a Joint Commission approved palliative care program. Methods: Retrospective review of patients with advanced lung cancer (stage III-IV) admitted to ICU in 2015-17. IRB approval was obtained. There were no exclusion criteria within this population. Areas assessed were age, stage, reason for admission, interventions, disposition, length of stay, days in the intensive care unit, palliative care consultation, code status, and documented end of life discussion. Results: A total of 13 patient met inclusion criteria. They were 38% male 62% female with a mean age of 67 years (SD: 14.9). All had prior diagnosis of advanced lung cancer and 92% were stage IV. The most common indication for admission was sepsis (38%). Less than half (46%) had a PCC, and fewer (31%) had a documented end of life care discussion. Even in the minority of patients with PCC, 33% received the PCC on day of death. Full code status was maintained in 77%. 53% expired during admission with only 57% of those that died having palliative care discussion. Conclusions: Even in a mature TJC certified PCC program, less than half of these terminally ill patients received a PCC. There is a chasm between ASCO's goal of early PCC and the reality of palliative care utilization in ICU admitted patients with advanced lung cancer. A possible solution is to initiate triggered palliative consultation for this high mortality population upon admission, with possible expansion to other terminally ill groups. In a world of electronic medical records, it should be possible to arrange a system to flag these patients for direct review by the palliative team to determine appropriateness and then notify the primary team in order to coordinate care.[Table: see text]

Influence of social determinants of health on patients with advanced lung cancer: a prospective cohort study

IntroductionSocioeconomic factors with an influence on human health are known as social determinants of health (SDH). There are some SDH studies in patients with lung cancer, but important exposures such...

OA14.03 Integrating Therapies into a Specialist Lung Cancer Nursing Team: An Evaluation

A diagnosis of advanced lung cancer inevitably results in deterioration in both health and functional status. This threatens a person’s independence and dignity and can be a burden to their family and carers. The lung cancer nursing team at Oxford identified a lack of timely therapy provision for their patient group and sought to improve this, concluding that having an occupational therapist (OT) in the team would significantly expand/diversify the service that could be offered to patients. Lung cancer therapy goals were identified as a) working with patients and carers to anticipate functional need rather than waiting for a crisis to occur b) providing a rapid, flexible and responsive service to those with existing needs and c) working in a keyworker role outside of traditional therapy expertise supporting patients at diagnosis, making treatment decisions and providing information. Funding was obtained from Macmillan Cancer Support for a three year project looking at delivering a new model of care. An Advanced Therapist Practitioner (ATP) with an OT background was recruited and embedded into the nursing team full time. Referrals were received from all members of the lung cancer MDT, the inpatient team, primary and palliative care. Interventions included home assessment, outpatient clinic review, breathlessness and anxiety management, provision of aids, support, education and advice. Data was gathered from a one year period when there were 305 new lung cancer diagnoses. 165 (54%) patients had identified therapy needs. A further 40 (13%) patients were seen by the ATP as part of her generic keyworker role. 205 referrals resulted in a total of 1005 interventions averaging 5 per person. Interventions were allocated to three levels ranging from simple telephone calls and liaison to complex case management. Average time from referral to first contact with the patient was half a day. The value of the role was measured in three ways: User Feedback Event, Satisfaction Questionnaire and a Stakeholder Questionnaire. Outcomes were overwhelmingly positive. Lung cancer patients have high functional needs. An ATP can become an integral part of traditional specialist nursing teams, is able to work in a keyworker capacity and is well accepted and used by the lung cancer MDT. The ATP role provides a strong bridge between primary and secondary care environments and preserves independence and dignity for longer. Evidence from users and stakeholders demonstrated high levels of satisfaction and quality of care.

Effectiveness of EGFR-tyrosine kinase inhibitors (TKI) versus EGFR-TKIs plus talc pleurodesis in preventing recurrence of malignant pleural effusion (MPE) in advanced lung adenocarcinoma.

e21684Background: Approximately 15% of patients have pleural effusion at the initial diagnosis of advanced lung cancer. The best treatment approach to prevent re-accumulation of symptomatic MPE aft...

Integrating Palliative Care Into the Care of Patients With Advanced Lung Cancer.

Lung cancer is the leading cause of death due to malignancy. Although lung cancer mortality has been decreasing in recent years, it remains substantially higher than other causes of cancer death. Median survival for patients with locally advanced non-small cell lung cancer, defined as lung cancer involving regional lymph nodes, is estimated to be approximately 10 to 17 months, and median survival for patients with metastatic disease is only 6 to 9 months. In addition, patients with advanced lung cancer often experience debilitating symptoms and poor quality of life. Pain, dyspnea, and fatigue are most frequently reported and affect at least 65% of patients with advanced lung cancer. Given this burden of symptoms and high mortality, patients and their families facing a diagnosis of advanced lung cancer are in need of support. Palliative care, with its focus on addressing the emotional, physical, and spiritual sources of suffering utilizing the expertise of an interdisciplinary team, can provide this comprehensive support. This review describes the role of supportive and palliative care integrated into the treatment of patients with a diagnosis of advanced lung cancer with sections focused on the evaluation and treatment of pain and dyspnea, approaches to challenging communication tasks, and the support of caregivers who care for patients with advanced lung cancer.

Clinically Relevant Gene Sequencing in Lung Cancer: Metastatic Non-Small Cell Lung Cancer

Clinically Relevant Gene Sequencing in Lung Cancer: Metastatic Non-Small Cell Lung Cancer

Preferences for aggressive care in underserved populations with advanced-stage lung cancer: looking beyond race and resuscitation

This paper examines the relationship between race, religiousness, spiritual well-being, antitumor treatment and preference for aggressive care among Black and White patients with advanced stage lung cancer receiving ambulatory cancer care in an urban setting. A cross-sectional exploration of patients enrolled in a Cleveland-based longitudinal study after initial diagnosis of advanced lung cancer were interviewed in Cleveland regarding religiousness, spiritual well-being, preferences for cardiopulmonary resuscitation (CPR), goals of aggressive care, and willingness to tolerate adverse health states. Receipt of antitumor treatment was identified from medical records. We analyzed data from 67 Black and 129 White patients (N=196). Regression analysis for CPR showed that race was not associated with preference for CPR (OR=1.12, CI 0.44-2.85). The odds of choosing CPR were three times higher among patients receiving antitumor treatment (OR=3.26, CI 1.12-9.44). Greater willingness to endure adverse health states was associated with higher spiritual well-being scores (b=0.12, CI 0.01-0.25). Choosing goals to extend life versus relieve pain was higher among persons with higher spiritual well-being as well (RRR=1.08, CI 1.01-1.16), yet the relationship with religiousness was negative (RRR=0.46, CI 0.22-0.98). After controlling for multiple factors, race was associated only with CPR, but not with other measures of preference for aggressive care. In addition, receipt of active antitumor treatment was positively associated with preference for CPR and spiritual well-being was important to setting end-of-life care goals and perspectives. Future directions for tailoring end-of-life care decision-making initiatives should move beyond race and discussions of CPR alone and focus on a full spectrum of patient beliefs and preferences at the end of life.

Provider Continuity Prior to the Diagnosis of Advanced Lung Cancer and End-of-Life Care

BackgroundLittle is known about the effect of provider continuity prior to the diagnosis of advanced lung cancer and end-of-life care.MethodsRetrospective analysis of 69,247 Medicare beneficiaries aged 67 years or older diagnosed with Stage IIIB or IV lung cancer between January 1, 1993 and December 31, 2005 who died within two years of diagnosis. We examined visit patterns to a primary care physician (PCP) and/or any provider one year prior to the diagnosis of advanced lung cancer as measures of continuity of care. Outcome measures were hospitalization, ICU use and chemotherapy use during the last month of life, and hospice use during the last week of life.ResultsSeeing a PCP or any provider in the year prior to the diagnosis of advanced lung cancer increased the likelihood of hospitalization, ICU care, chemotherapy and hospice use during the end of life. Patients with 1–3, 4–7 or >7 visits to their PCP in the year prior to the diagnosis of lung cancer had 1.0 (reference), 1.08 (95% CI; 1.04–1.13), and 1.14 (95% CI; 1.08–1.19) odds of hospitalization during the last month of life, respectively. Odds of hospice use during the last week of life were higher in patients with visits to multiple PCPs (OR 1.10: 95% CI; 1.06–1.15) compared to those whose visits were all to the same PCP.ConclusionProvider continuity in the year prior to the diagnosis of advanced lung cancer was not associated with lower use of aggressive care during end of life. Our study did not have information on patient preferences and result should be interpreted accordingly.

A Pilot Study To Investigate Adherence to Long-Acting Opioids among Patients with Advanced Lung Cancer

Uncontrolled pain remains prevalent in patients with advanced cancer and has been associated with worse quality of life and greater health care utilization. Poor adherence to analgesics may represent a modifiable barrier to pain management. This pilot study aimed to establish feasibility/utility of evaluating self-reported adherence to long-acting (LA) opioids in patients with advanced lung cancer, and to explore rates and correlates of adherence. Consecutive patients attending an ambulatory thoracic oncology clinic with a diagnosis of advanced lung cancer and a current LA opioid regimen were approached to complete a brief questionnaire during their clinic visit. Participants reported LA opioid adherence during the past 4 weeks (0%-100%) and knowledge of their LA opioid regimen, and completed the Patient Health Questionnaire-2 (PHQ-2) depression screen. Demographic and clinical information were confirmed via electronic health record review. Fifty-four eligible patients were approached to reach our target sample (n=50; enrollment=92.6%). Self-reported adherence to LA opioids was 85.4% (standard deviation [SD]=21.0). Twenty-eight percent reported a frequency of medication use that did not match the prescribed daily frequency. Lower adherence was associated with inaccurate frequency (p=0.004), positive depression screen (p=0.005), and older age (p=0.04). Our results demonstrate the feasibility of integrating self-report assessments of LA opioid adherence into a thoracic oncology clinic. Patients reported high adherence, but more than one-quarter did not accurately report the prescribed frequency of daily doses. Understanding of LA opioid regimens may be a critical indicator of adherence in patients with advanced cancer.

Do Complex Mutations of the Epidermal Growth Factor Receptor Gene Reflect Intratumoral Heterogeneity?

In our clinical practice, two different epidermal growth factor receptor (EGFR) gene mutations are occasionally found in a single tumor sample. Such co-occurring EGFR mutations have been termed “complex mutations,” and we have previously reported the incidence and efficacy of gefitinib for patients with complex mutations.1Hata A Yoshioka H Fujita S et al.Complex mutations in the epidermal growth factor receptor gene in non-small cell lung cancer.J Thorac Oncol. 2010; 5: 1524-1528Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar In our previous article, we discussed the cause of complex mutations and speculated on the existence of intratumoral heterogeneity for EGFR mutations. We recently encountered three cases that support our hypothesis and herein present these cases. Case 1 was a 68-year-old man. He received a computed tomography-guided lung biopsy due to a suspicion of lung cancer. We performed a fine needle aspiration, followed by a core needle biopsy through a guide needle to obtain both cytological fluid and histological tissue (Figure 1). Although both cytology and histology revealed adenocarcinoma cells, we accidentally performed EGFR mutational analysis on both specimens. Interestingly, only a point mutation in exon 21 (L858R) was detected in the cytology, but complex mutations consisting of a point mutation in exon 18 (G719S) and L858R were detected in the histology. After a diagnosis of locally advanced disease, the patient underwent concurrent chemoradiation therapy. After the treatment, he has been observed and has not yet received EGFR-tyrosine kinase inhibitor (TKI) therapy. Case 2 was a 66-year-old woman. She was diagnosed with lung adenocarcinoma and underwent surgery as the initial therapy. EGFR mutational analysis in the surgical tissue revealed complex mutations consisting of a deletional mutation in exon 19 (Del-19) and L858R. After recurrence, she underwent multiple chemotherapies including EGFR-TKIs. In the course of treatment, she complained of gait disturbance and neck stiffness. Brain magnetic resonance imaging showed leptomeningeal metastases (Figure 2), and a lumbar puncture was performed. Unexpectedly, Del-19 disappeared, and only L858R was detected by EGFR mutational analysis of malignant cells in the cerebral spinal fluid. Rechallenge treatment with erlotinib was administered, and the clinical benefit has continued for 4 months. Case 3 was an 81-year-old man. He was initially diagnosed with lung adenocarcinoma with pleural disseminations. EGFR mutational analysis of the primary tumor showed complex mutations consisting of Del-19 and L858R. Considering the patient's age, gefitinib was chosen as the first-line treatment. Primary tumor and pleural disseminations markedly responded to gefitinib for approximately 20 months. However, the right pleural effusion has recently increased (Figure 3), and the cytology of pleural effusion revealed adenocarcinoma cells. Similarly, Del-19 disappeared, and both L858R and a point mutation in exon 20 (T790M) were detected by EGFR mutational analysis of the pleural effusion. Chest tube drainage has been carried out. Case 1 implies the existence of heterogeneous EGFR mutations in a single tumor: cytological fluid cells harboring only L858R and histological tissue cells harboring both G719S and L858R simultaneously existed in a single tumor. The intratumoral heterogeneity of EGFR mutation has been previously reported; both EGFR mutated and wild-type malignant cells were confirmed in a single tumor tissue in the report.2Sakurada A Lara-Guerra H Liu N et al.Tissue heterogeneity of EGFR mutation in lung adenocarcinoma.J Thorac Oncol. 2008; 3: 527-529Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar In cases 2 and 3, although complex mutations consisting of Del-19 and L858R were detected at the initial EGFR mutational analysis, Del-19 has disappeared and L858R remained after EGFR-TKI treatments. Higher sensitivity to EGFR-TKIs in patients with Del-19 than L858R has been demonstrated in several reports.3Jackman DM Yeap BY Sequist LV et al.Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib.Clin Cancer Res. 2006; 12: 3908-3914Crossref PubMed Scopus (486) Google Scholar If Del-19 and L858R cells had existed separately, Del-19 cells would have responded to EGFR-TKIs better than L858R cells, and L858R cells might have remained. Our present cases exhibiting these complex mutations suggest the intratumoral heterogeneity of EGFR mutations. Considering intratumoral heterogeneity consisting of EGFR-sensitive-mutated cells and wild-type or EGFR-resistant-mutated cells, the detection of EGFR mutations using a highly sensitive polymerase chain reaction method from small biopsies may not always reflect whole tumor sensitivity to EGFR-TKIs.4Travis WD Rekhtman N Riley GJ et al.Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift.J Thorac Oncol. 2010; 5: 411-414Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar However, our data were taken from only a few cases, and further research is needed. The clinical significance of intratumoral heterogeneity warrants future studies.

EUS-guided FNA for the diagnosis of advanced lung cancer

A majority of patients with lung cancer are incurable but are symptomatic and may benefit from palliative therapy. Currently available diagnostic methods are either too risky or unsuccessful in obtaining a tissue diagnosis in up to 30% of patients. To evaluate the role of EUS-guided FNA in obtaining a tissue diagnosis in patients with advanced lung cancer. Prospective, uncontrolled. Veterans Administration Medical Center. Patients with suspected lung cancer who were not candidates for curative therapy were prospectively identified. CT scans were reviewed, and patients with lesions considered suitable for sampling by EUS were enrolled. Outcomes were analyzed by a final tissue diagnosis or by serial imaging. Sixty-nine patients met inclusion criteria, of which 3 refused participation. The remaining 66 patients constituted the study population. EUS was technically successful in 95% of patients. A final diagnosis was based on tissue in 63 of 66 patients, serial imaging in 1 of 66 patients, and was unavailable in 2 of 66 patients. A lung mass was sampled in 21 patients, and a metastatic lesion was sampled in 45 patients. EUS made a correct diagnosis in 55 of 64 patients (86%, 95% confidence interval [CI] 77%-93%), including 24% that had undergone a failed prior attempt at diagnosis. The sensitivity of EUS was 86%, and the specificity was 100%. Sampling a metastasis was more likely to yield a correct diagnosis than sampling a lung mass (P = .02). Two self-limited complications were noted during the study. EUS was an accurate and a safe method for obtaining a tissue diagnosis in patients with advanced incurable lung cancer.