Anaplastic Cancer Research Articles

Five-year relative survival and determinants of excess mortality in patients with head and neck and thyroid cancers: A population-based study from Golestan province, Northern Iran

BackgroundWe aimed to assess relative survival (RS) and determinants of excess mortality rate in patients with head and neck squamous cell carcinomas (HNSCC) and thyroid cancer in Golestan province, Northern Iran. MethodsWe recruited new primary HNSCC and thyroid cancer cases from Golestan, 2006–2016. Five-year age-standardized RS with their 95% confidence intervals (CIs) were calculated. The relationships between different variables with excess mortality rates were assessed by estimating adjusted excess hazard ratios (aEHRs) with their 95% CIs. ResultsOverall, 718 cases of HNSCC and 386 thyroid cancer cases were enrolled. Five-year age-standardized RS (95% CI) were 36% (31−41) and 61% (52−69) in HNSCC and thyroid cancer patients, respectively. There were significant relationship between excess mortality rates in HNSCC patients with metastasis (aEHR= 3.31; 95%CI: 2.26–4.84), treatment type (4.19; 2.54–6.91, for no treatment as compared to receiving both surgery and chemoradiotherapy), age (2.16; 1.57–2.96, for older age group) and smoking (2.00; 1.45–2.75, for smokers as compared to non-smokers). Determinant of the excess mortality in thyroid cancer patients included metastasis (19.65; 8.08–47.79), tumor morphology (12.27; 4.62–32.58, for anaplastic cancer as compared to papillary cancer), treatment type (8.95, 4.13–19.4, for no treatment as compared to receiving both surgery and iodine therapy) and age (2.31; 1.17–4.54, for older age group). ConclusionOur findings suggested low RS for thyroid cancer in our population, while the estimates for HNSCC were comparable with other population. Metastasis, treatment type and age were determinants of mortality both in thyroid and HNSCC patients.

1175P Pharmacokinetics of ensartinib in advanced solid tumors and anaplastic lymphoma kinase-positive non-small cell lung cancer

Ensartinib is a novel and potent anaplastic lymphoma kinase (ALK) inhibitor. This study aimed to develop a population pharmacokinetic (POP-PK) model for ensartinib in advanced solid tumors and ALK-positive non–small cell lung cancer (NSCLC) and to investigate the exposure-response (E-R) and dose-response (D-R) relationships for selected efficacy and safety endpoints.

Efficacy of lorlatinib after alectinib-induced interstitial lung disease in a patient with anaplastic lymphoma kinase-positive non-small cell lung cancer: a case report

BackgroundAnaplastic lymphoma kinase tyrosine kinase inhibitors are standard therapeutic agents prescribed for anaplastic lymphoma kinase-positive non-small cell lung cancer, and treatment with these agents has been shown to contribute to long-term survival in patients. However, there is no consensus regarding the course of treatment after the onset of anaplastic lymphoma kinase tyrosine kinase inhibitors related drug-induced interstitial lung disease.Here, we present a case of successful lorlatinib treatment after the onset of drug-induced interstitial lung disease caused by alectinib.Case presentationA 57-year-old Japanese man was diagnosed with stage IVB non-small cell lung cancer by bronchoscopy, but gene mutation testing could not be performed because of the small amount of specimen. After diagnosis, first-line therapy with cisplatin/pemetrexed was initiated, but the patient developed renal dysfunction. Bronchoscopy was performed again to guide further treatment, and the non-small cell lung cancer was found to be anaplastic lymphoma kinase positive. Alectinib was started after the onset of progressive disease, but it resulted in drug-induced interstitial lung disease, necessitating alternative treatments. He subsequently received nanoparticle albumin bound paclitaxel, which was halted in view of the renal dysfunction. Thereafter, lorlatinib was administered, which was continued without drug-induced interstitial lung disease relapse.ConclusionSince alectinib can occasionally cause drug-induced interstitial lung disease, as in the present case, lorlatinib may be an option to continue treatment in patients without other treatment alternatives.

Radiomic-signature changes after early treatment improve the prediction of progression-free survival in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.

The prognosis of lung cancer varies widely, even in cases wherein the tumor stage, genetic mutation, and treatment regimens are the same. Thus, an effective means for risk stratification of patients with lung cancer is needed. To develop and validate a combined model for predicting progression-free survival and risk stratification in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with ensartinib. We analyzed 203 tumor lesions in 114 patients and evaluated average radiomic feature measures from all lesions at baseline and changes in these features after early treatment (Δradiomic features). Combined models were developed by integrating clinical with radiomic features. The prediction performance and clinical value of the proposed models were evaluated using receiver operating characteristic analysis, calibration curve, decision curve analysis (DCA), and Kaplan-Meier survival analysis. Both the baseline and delta combined models achieved predictive efficacy with a high area under the curve. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the combined models for tumor progression prediction. In the Kaplan-Meier analysis, the delta and baseline combined models, Δradiomic signature, and two selected clinical features could distinguish patients with a higher progression risk within 42 weeks. The delta combined model had the best performance. The combination of clinical and radiomic features provided a prognostic value for survival and progression in patients with NSCLC receiving ensartinib. Radiomic-signature changes after early treatment could be more valuable than those at baseline alone.

Outcomes and Toxicities of Nonmedullary Thyroid Tumors Treated with Proton Beam Radiation Therapy.

PurposeProton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck.MethodsFrom our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities.ResultsMedian follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities.ConclusionsProton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

Anaplastic Cancer: Our Experience.

Anaplastic thyroid carcinoma (ATC) is a rare thyroid malignancy with a dire prognosis, nearly 100% disease specific mortality and a median overall survival less than 6months. In view of the limited data from India on anaplastic thyroid cancer, we conducted this audit to analyze the treatment pattern, outcomes and factors influencing it. This is a retrospective analysis of outcomes of patients treated in a single institution between January 2008 and December 2020. Baseline characteristics, treatment received, and outcomes among adult patients with ATC were collected. Progression free survival (PFS) and overall survival (OS) were analyzed. SPSS version 20 and RStudio version 3.1.1 were used for analysis. In this cohort of 134 patients, the median age at diagnosis was 59years, with 63.4% of them being females. At presentation, 70.9% of them had good performance status (PS 0-1). Only 38.8% received treatment with curative intent (either surgery fb adjuvant or neoadjuvant chemotherapy fb surgery and adjuvant or definitive chemoradiotherapy) while 61.2% patients received palliative treatment (either palliation alone or palliative chemotherapy or palliative surgery or palliative RT). Predominant pattern of progression was local progression (79.8%). Median PFS and OS of the overall cohort were 58days and 80days respectively. PFS and OS were significantly better in patients treated with curative intent vs palliative intent (116 and 134days vs 45 and 50days; p = 0.00 and 0.00 respectively). Among patients treated with curative intent, OS was significantly better in patients undergoing surgery vs CTRT (155 vs 76days; p = 0.03). Among patients treated with upfront surgery, both PFS and OS were better with the addition of adjuvant CTRT/RT vs no adjuvant (332 and 540days vs 55 and 91days; p = 0.00 and 0.003 respectively). ATC is a rare cancer with dismal prognosis. Local therapy with surgery followed adjuvant seems to be associated with the better outcomes. Systemic therapy seems to be a better option for palliation. Our data reflects the real world data of this rare cancer.

CO26 Efficacy and Safety of First-Line Treatments for Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Systematic Review and Indirect Treatment Comparison

To evaluate the relative efficacy and safety of brigatinib compared with other ALK inhibitors for the first-line treatment of ALK-positive non-small cell lung cancer (NSCLC) patients.

Expert consensus on ensartinib in the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer

The mutation rate of anaplastic lymphoma kinase (ALK) in patients with non-small cell lung cancer is 3% to 7%. Due to its low mutation rate and better long-term survival compared with epidermal growth factor receptor-positive non-small cell lung cancer patients, therefore, it's called "diamond mutation". At present, there are three generations of ALK tyrosine kinase inhibitor (TKI) drugs in the world. The first-generation ALK-TKI drug approved in China is crizotinib, and the second-generation drugs are alectinib, ceritinib and ensartinib. Among them, ensartinib is an ALK-TKI domestically developed, and its efficacy is similar to that of alectinib. The main adverse event is transient rash, and compliance to ensartinib is better from the perspective of long-term survival of patients. The manifestation of rash caused by ensartinib is different from that of other ALK-TKI drugs. In order to facilitate clinical application and provide patients with more treatment options, under the guidance of the Committee of Cancer Rehabilitation and Palliative Care of China Anti-Cancer Association, this article collects and summarizes the common adverse reactions of ensartinib. Based on the clinical practice, a clear adverse classification and specific treatment plan are formulated, in order to provide a corresponding reference for clinicians to make more comprehensive clinical decisions.

PET positive tattoo lymphadenopathy: a case report and review of the literature

We present a case of positron emission tomography (PET)–avid internal mammary lymphadenopathy, prompting open excisional biopsy of the lymph node in the setting of concern about breast-implant associated anaplastic large cell lymphoma (BIA-ALCL) or breast cancer recurrence. Histopathological examination revealed reactive lymphadenopathy with tattoo ink and no malignancy. We undertook a review of the literature to investigate the frequency of tattoo ink related PET-avid lymphadenopathy, and false positive PET scan results from tattooing. Lymphadenopathy related to tattoo ink has been reported previously, however this is the only case of benign PET positive tattoo lymphadenopathy resulting in unnecessary invasive surgery reported to date.

Characteristics of malignant neoplasms of the hepatobiliary system in the cohort of occupationally-exposed workers

Introduction. The etiology of malignant neoplasms (MN) of the hepatobiliary system is multifarious, so when assessing the impact of ionizing radiation on the occurrence of tumors of this localization, non-radiation factors should be considered. The aim of the study was to describe cases of hepatobiliary system disease in the cohort of employees hired at the main plants of FSUE Mayak Production Association (PA «Mayak») in 1948-1982, who were exposed to occupational chronic radiation. Materials and Methods. The cohort under study included 22,377 persons (25% were women). The frequency of individual risk factors was compared among morphologically confirmed cases of hepatobiliary cancer and among workers who had not been ill with tumors of the indicated localization. Results. Up to December 31, 2018, the cohort had 59 cases of liver MCC (59% hepatocellular carcinoma, 17% cholangiocarcinoma, 25% hemangiosarcoma, and 2% anaplastic cancer) and 34 cases of gallbladder and biliary tract MCC (100% adenocarcinoma). The incidence of chronic diseases of gallbladder and biliary tract, cholelithiasis was statistically significantly higher among cases of hepatobiliary MNS in comparison with uninfected workers. In addition, there was a higher share of persons who had contact with harmful industrial factors before employment at PA «Mayak», as well as those with chronic liver diseases, excessive body weight and obesity among liver cancer patients. Doses of occupational exposure were highest in workers with liver hemangiosarcomas. Discussion. The data were obtained testifying to a possible role of non-radiation factors and ionizing radiation in the development of hepatobiliary cancer in the workers of the cohort under study. A peculiarity of the cohort is a high proportion of hemangiosarcomas in the structure of hepatic cancer. Conclusion. The non-radiational factors that, along with occupational exposure, could influence the incidence of hepatobiliary cancer among PA «Mayak» workers have been singled out. An analysis of risk caused by radiation and non-radiation factors is required to clarify the results of the study.

Chemotherapy versus alectinib for the treatment of crizotinib-pretreated ALK-positive patients with non small cell lung cancer: A protocol for systematic review and meta-analysis.

There are no evidence-based data in the literature to demonstrate that alectinib shows a clinically relevant advantage over chemotherapy in anaplastic lymphoma kinase-positive non-small cell lung cancer pretreated with crizotinib. Therefore, we designed this systematic review and meta-analysis protocol to reveal whether the safety and efficacy of alectinib are indeed superior to chemotherapy alone in this special group of patients. This protocol will be written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. We will search databases from Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library from their inception to June 2022, restricting them to human subjects and clinical trials. Outcomes include progression-free survival, central nervous system progression, and incidence of adverse events. Pooled analyses will be calculated using fixed-effect models, whereas random-effect models will be applied in case of significant heterogeneity across studies. Any disagreements will be discussed and resolved in discussions with the third reviewer. We hypothesized that alectinib would be superior to chemotherapy in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer pretreated with crizotinib. The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. 10.17605/OSF.IO/PQF53.

Review of Therapeutic Strategies for Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer.

Simple SummaryAnaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) was first reported in 2007. Following the development of crizotinib as a tyrosine kinase inhibitor (TKI) targeting ALK, the treatment of advanced NSCLC with ALK-rearrangements has made remarkable progress. Currently, there are five ALK-TKIs approved by the FDA, and the development of new agents, including fourth-generation TKI, is ongoing. Clinical trials with angiogenesis inhibitors and immune checkpoint inhibitors are also underway, and further progress in the treatment of ALK-rearranged advanced NSCLC is expected. The purpose of this manuscript is to provide information on the recent clinical trials of ALK-TKIs, angiogenesis inhibitors, immune checkpoint inhibitors, and chemotherapy, to describe tissue and liquid biopsy as a method to investigate the mechanisms of resistance against ALK-TKIs and suggest a proposed treatment algorithm.Non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase rearrangement (ALK) was first reported in 2007. ALK-rearranged NSCLC accounts for about 3–8% of NSCLC. The first-line therapy for ALK-rearranged advanced NSCLC is tyrosine kinase inhibitors (TKI) targeting ALK. Following the development of crizotinib, the first ALK-TKI, patient prognosis has been greatly improved. Currently, five TKIs are approved by the FDA. In addition, clinical trials of the novel TKI, ensartinib, and fourth-generation ALK-TKI for compound ALK mutation are ongoing. Treatment with angiogenesis inhibitors and immune checkpoint inhibitors is also being studied. However, as the disease progresses, cancers tend to develop resistance mechanisms. In addition to ALK mutations, other mechanisms, including the activation of bypass signaling pathways and histological transformation, cause resistance, and the identification of these mechanisms is important in selecting subsequent therapy. Studies on tissue and liquid biopsy have been reported and are expected to be useful tools for identifying resistance mechanisms. The purpose of this manuscript is to provide information on the recent clinical trials of ALK-TKIs, angiogenesis inhibitors, immune checkpoint inhibitors, and chemotherapy to describe tissue and liquid biopsy as a method to investigate the mechanisms of resistance against ALK-TKIs and suggest a proposed treatment algorithm.

139 - Using qualitative research to determine the impact of brain metastases (BM) on the advanced anaplastic lymphoma kinase positive non-small cell lung cancer (ALK+ NSCLC) patient experience

139 - Using qualitative research to determine the impact of brain metastases (BM) on the advanced anaplastic lymphoma kinase positive non-small cell lung cancer (ALK+ NSCLC) patient experience

The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer treated with first-line ALK inhibitor

BackgroundAnaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC). However, reliable biomarkers to predict the prognostic role of this treatment are lacking. The Pan-Immune-Inflammation Value (PIV) has recently been demonstrated as a novel comprehensive biomarker to predict survival of patients with solid tumors. Our study aimed to evaluate the prognostic power of PIV in this group of patients. Patients and methods94 patients with advanced ALK-positive NSCLC who received first-line ALK inhibitors were enrolled in this study. PIV was calculated as the product of peripheral blood neutrophil, monocyte, and platelet counts divided by lymphocyte count. Kaplan-Meier method and Cox hazard regression models were used for survival analyses. ResultsThe 1-year progression-free survival (PFS) was 63.5%, and the 5-year overall survival (OS) rate was 55.1%. Patients with higher PIV, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) had worse PFS in univariate analysis, but only the PIV (hazard ratio [HR] = 2.90, 95% confidence interval [CI]: 1.79–4.70, p < 0.001) was an independent prognostic factor in multivariate analysis. Similarly, patients with higher PIV, NLR, PLR, and SII had a worse OS in the univariate analysis, but only the PIV (HR = 4.70, 95% CI: 2.00–11.02, p < 0.001) was significantly associated with worse OS in multivariate analysis. ConclusionPIV is a comprehensive and convenient predictor of both PFS and OS in patients with ALK-positive advanced NSCLC who received first-line ALK TKIs. Prospective clinical trials are required to validate the value of this new parameter.

ANALYSIS OF THYROID CANCER INCIDENCE AND MORTALITY TRENDS AMONG THE RESIDENTS OF THE SUMY REGION

Introduction. Thyroid cancer ranks ninth in the structure of malignant neoplasms. Since the 1980s, most countries in the world have seen a rapid increase in the incidence rate and a relatively stable or even decreasing mortality rate. The objective of our study was to analyze the thyroid cancer morbidity and mortality trends in the Sumy region during 2014–2021, to study the prevalence of histological variants and sex-age-specific characteristics, and to compare them with all-Ukrainian and global data. Study results. According to the National Cancer Registry of Ukraine, 24,626 people were diagnosed with thyroid cancer between 2014 and 2021, including 4,556 men (18.5%) and 2,0070 women (81.5%). On average, 3078.25 ± 136.15 people were diagnosed per year. The incidence rate among women is 3.8 times higher than among men. The average incidence rate in Ukraine in 2014–2021 was 6.5 per 100,000 population, while in the Sumy region – 8.9 per 100,000 population. The average mortality rates among residents of the Sumy region and Ukraine did not differ and amounted to 0.4 per 100,000 population. A distinctive feature was represented by the lower male and higher female mortality rates in the Sumy region compared to all-Ukrainian indicators (0.2 versus 0.3 per 100,000 population and 0.6 versus 0.4 per 100,000 population, respectively). The study of histological types of thyroid malignancies demonstrated that papillary variant was most common (70.5 to 81.9%). The specific share of follicular cancer ranged from 12.8 to 19.2%. The medullary variant occured much less often – in 1.5 to 4.6% of cases, while undifferentiated and squamous cell cancer was extremely rare (0.2 to 3.3% of cases). In Buryn district, Velyka Pysarivka district, Konotop district, Krasnopillia district, Krolevets district, Lebedyn district, Nedrygailiv district, Putyvl district, Sumy district, Trostyanets district and the city of Sumy, a significantly higher incidence rate was observed. Women aged 50–64 and men aged 55–69 are most often affected in Ukraine. The highest mortality rate is reported for the age range of 70–84 years for both males and females. Conclusions. During 2014–2021, the incidence and mortality rates among the population of Ukraine remained at a stable level and were lower compared to global indicators. Since 2017, the Sumy region has been presenting with a decrease in the incidence rate, which corresponds to European trends. In the Sumy region, papillary thyroid cancer remains the most common histological variant. In general, the shares of papillary, follicular, medullary, and anaplastic cancers are consistent with the European figures. In general, the age trends in Ukraine and other countries of the world are similar.

Current Insights on the Treatment of Anaplastic Lymphoma Kinase-Positive Metastatic Non-Small Cell Lung Cancer: Focus on Brigatinib.

Rearrangement of anaplastic lymphoma kinase (ALK) gene is detected in approximately 5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors targeting ALK have significantly improved the prognosis of these patients. However, most patients experienced disease progression within a few years due to acquired resistance. Brigatinib is a second-generation ALK inhibitor effective in presence of several ALK mutations with demonstrated activity against central nervous system metastases. Currently, brigatinib is approved to treat ALK-positive metastatic NSCLC patients not previously treated with ALK inhibitors and patients who have progressed on or are intolerant to crizotinib. In this review, we provide a summary of results from clinical trials involving brigatinib, and we discuss its possible role in the management of ALK-positive NSCLC in the following years.

POSB151 Brigatinib As a Leading Option to Manage Previously Not Treated Patients with Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer (ALK+ NSCLC) in Portugal

ALK+ NSCLC is an aggressive subtype of lung cancer with high rates of Central Nervous System (CNS) metastasis, with 15-35% of patients presenting brain metastases at diagnosis, leading to a major clinical burden and a high economic impact on national healthcare systems (NHS). Crizotinib, a first-generation tyrosine kinase inhibitor (TKI), currently used in the Portuguese setting as first-line (1L) treatment, has shown limited CNS efficacy – 70% of patients experience CNS disease progression during treatment with crizotinib.

Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer.

IntroductionThe outcomes after gamma knife radiosurgery (GKRS) were retrospectively analysed in patients with brain metastases from anaplastic lymphoma kinase (ALK) rearrangement-positive and epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) to evaluate the efficacy, safety and difference for overall survival and local tumor control.MethodsThe medical records were retrospectively reviewed of 607 patients (25 ALK-positive, 171 EGFR-positive, and 411 wild type) with 2959 tumors who had undergone GKRS.ResultsThe median overall survival time after initial GKRS was 14 months. Driver gene mutation-positive patients had significantly longer overall survival than wild type patients (p < 0.0001), and ALK-positive patients survived significantly longer than EGFR-positive patients (p = 0.04). Multivariate analysis showed the unfavorable factors significantly affecting overall survival outcomes were older age, lower Karnofsky Performance Status score, multiple intracranial metastases, uncontrolled primary cancer, uncontrolled extracranial metastases, no administration of immune checkpoint inhibitors, and driver gene mutation-negative cases. Seventy-three patients died of uncontrolled brain metastases at a median of 12 months. Driver gene mutations had no influence (p = 0.33), and ALK-positive and EGFR-positive patients showed no significant difference in neurological survival (p = 0.83). A total of 174 patients demonstrated distant brain control failure at a median of 15 months. ALK-positive type was significant compared with EGFR-positive type (p = 0.047), but driver gene mutation-positive and -negative types showed no significant difference in the development of new brain metastases (p = 0.2). The median tumor volume was 1.06 cm3 in the driver gene mutation-positive type and 1.85 cm3 in wild type. The median marginal dose was 20 Gy in both types. The 6-, 12-, and 24-month local tumor control rates were 97.3%, 96.1%, and 95.9%, respectively. Driver gene mutations had a significantly positive impact on local tumor control (p = 0.001), and ALK-positive and EGFR-positive types showed no significant difference (p = 0.95). A total of 193 tumors had radiation injury at a median of 12 months after GKRS. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 8.1%, and 8.7%, respectively. Driver gene mutations significantly induced radiation damage (p = 0.021), and the ALK-positive type was affected more than the EGFR-positive type (p = 0.02).ConclusionsALK rearrangement-positive NSCLC patients tended to have significantly longer survival, but had higher incidence of new intracranial metastases due to long-term survival after GKRS, compared with EGFR mutation-negative and driver gene mutation-negative NSCLC patients. GKRS induced significantly satisfactory local tumor control in driver gene mutation-positive tumors but GKRS-related complication frequency was higher, especially in ALK-positive NSCLC patients. Therefore, more careful imaging follow-up is necessary after GKRS for patients with driver gene mutation-positive NSCLC.

Pharmacokinetically-guided dosing to improve the efficacy of brigatinib in non-small cell lung cancer patients.

Brigatinib was recently approved for the treatment of anaplastic lymphoma kinase‐positive non‐small cell lung cancer and is dosed according to a one‐dose‐fits‐all paradigm. We aimed to identify a pharmacokinetically‐guided precision dosing strategy to improve treatment response with brigatinib through simulations using a previously published pharmacokinetic‐pharmacodynamic model. Dosing strategies explored were the approved 180 mg QD; the highest tolerable dose tested in clinical trials: 240 mg QD; and two precision dosing strategies targeting the median trough concentrations following 180 mg QD, and 240 mg QD. We investigated the impact of alternative dosing regimens on progression‐free survival (PFS), overall survival (OS) and the probability of developing a grade ≥2 rash or grade ≥2 amylase increase. Median PFS and OS increased by 1.6 and 7.8 months, respectively between the currently approved dosing strategy and precision dosing to the median trough concentration of the 240 mg dosing strategy, with only a minor increase in the probability of developing toxicity.

Thyroid cancer in the Democratic Republic of the Congo: Frequency and risk factors

BackgroundThe prevalence of thyroid cancer is increasing steadily in most countries, partly due to better, earlier diagnosis. However, there is little data for developing countries, where the technical platform is often very limited, especially in Africa. ObjectivesTo assess the frequency of thyroid cancer in the Democratic Republic of the Congo (DRC) and to analyze the epidemiological, clinical, and ultrasound risk factors. Material and methodsThis is a multicenter cross-sectional study of 594 patients operated on for a thyroid mass from 2005 to 2019, in 35 centers in the DRC and for whom histopathological analyses were performed. ResultsThe frequency of thyroid cancers in our cohort was 20%, mostly in patients over the age of 40 (62% of patients). These cancers were mainly diagnosed at the clinical stage, due to the presence of palpable masses. Papillary cancer was the most common (67.2% of patients), followed by follicular cancer (28% of cases). We found a high prevalence of anaplastic cancer (7.6%). These frequencies are probably the consequence of the fact that histopathological analyses are not systematically performed in the DRC, but mostly on tissues that the thyroid surgeons suspect to be malignant. Age ≥60 years, the presence of adenopathies upon palpation or on ultrasound, the solid nature and hypoechogenicity of nodules, the presence of macronodules and calcifications were the factors independently associated with the diagnosis of cancer in the study population. ConclusionsIn this first study performed in the DRC, we have found that thyroid cancer is common. It is mainly detected at clinical stages, with patients over the age of 40 years and women being the most affected. The histopathology distribution differs from that in developed countries, with a lower prevalence of papillary cancer and a higher prevalence of the anaplastic type. In developing countries, it appears necessary to introduce the use of more precise diagnostic tools for thyroid cancer and also, to reinforce the improvement of known, controllable risk factors such as iodine deficiency.