bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle MASS and mortality in cancer patients.
Authors: Salas Claudio , De La Maza Maria PIA , von Geldern Paula , Silva Claudio , Alvayay Pablo , Berkovits Alejandro
Published: May 2019

e18290

Background: Detection and prevention of cancer cachexia during oncologic treatment is an important issue in cancer patients care. AIM: To analyze the relation between overall survival and nutritional status assessed both by subjective and objective methods, in a prospective cohort of oncologic patients. Methods: Between 2012-2014 all patients under treatment in the Oncology Unit of Clinica Alemana de Santiago were invited to participate in this study, and follow-up was completed August 2018. Exclusion criteria were terminal phase patients, or those with cognitive deterioration. Apart from recording demographic, clinical and nutritional data, whenever possible, recent computed tomographic images were analyzed through Slice O Matic, at the level of the third lumbar vertebra, for measurement of abdominal fat and muscle area. Muscle Mass Index (MMI) was calculated as muscle area/squared height. The control group was composed by 130 healthy subjects 18-40 years, whose computed tomography images were obtained as part of the trauma protocol. The cutoff for sarcopenia was MMI < -1 SD respect control subjects. In addition, nutritional status was assessed through anthropometric measurements and the Patient Generated Subjective Global Assessment (VGSGP). Results: We included 103 patients, predominant cancer sites were digestive, haematologic and lung; average survival was 33 ± 23 months. The sample was divided in 2 groups (TNM stages 1 and 2 versus 3 and 4). MMI in control subjects was significantly higher than values obtained from 64 oncologic patients with available CT scans, while fat area, specifically visceral, was the opposite. VGSGP scores correlated negatively and significantly with MMI (p < 0.001). According to univariate analysis, survival time was inversely associated with age among male patients ( p = 0.002), cancer stage in both genders p < 0.01), VGSGP (p < 0.01), and positively associated with MMI, only among men (p = 004). Kaplan Meir survival estimates were significant both sarcopenia and cancer stage. According to Cox regression, both sarcopenia and cancer stage were significant predictors of mortality, without any effect of age or sex. Conclusions: Both sarcopenia and cancer stage are predictors of survival during treatment of cancer.
Strategies for reducing grade 2 and 3 adverse events due to immunotherapy in a Spanish university hospital.
Authors: Gomez Ana , Gómez Solana Paloma , Ruiz Elena , Anton Antonio , Aranda Enrique , Camps Carlos , Constenla Manuel , Cruz Juan Jesús , Díaz-Rubio Eduardo , Feyjoo Margarita , García Foncillas Jesús , Gascon Pedro , Guillem Vicente , Lopez Rafael , Lugo Ilse , Carrato Alfredo
Published: May 2019

e18295

Background: To develop an improvement project, the Lung Cancer Unit of Ramón y Cajal Hospital (Madrid) analyzed 45 patients treated with immunotherapy in 2017 and detected that 55% presented moderate-to-severe Adverse Events (AEs). Consequently, a specialized team from Ramon y Cajal Hospital and the ECO Foundation proposed to identify improvement areas that reduce grade 2 (G2) and 3 (G3) AEs. ECO is a collaboration of experts representing the major Spanish hospitals in the pursuit of excellence in cancer treatment. Methods: The team used as an instrument the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP). A data collection process was conducted before attending the first out of three sessions of the QTP with the revision of medical records from lung cancer patients. The goal for the final QTP session in June 2018 was to reduce G2 and G3 AEs by 25%, by standardizing patient education sessions using ASCO guidelines for the management of immune-related AEs. Results: The data collected showed that G2 and G3 AEs had an impact on quality of care, specifically a treatment delay in 31% of patients, unscheduled visits in 19%, serious complications in 11% and patient dissatisfaction with the reporting system. The team created a cause and effect diagram, in which the most relevant causes were inadequate patient knowledge and a lack of communication with patients between visits. A run chart of the percentage of G2 and G3 AEs during 2017 displayed that G2 AEs were higher during January and August; and G3 AEs in February and December. The team, including patient advocates, prioritized the implementation of these short-term measures for patients: improvement of education, education follow-up, satisfaction questionnaire development and AE knowledge test. By June 2018, the resulting value of the “(mean + range)/standard deviation” formula for AEs perceived knowledge in patients increased from 5.4 to 11.1 points, the same value for patients’ AEs knowledge increased from 7.3 to 13.8 points, the percentage of G2 AEs reduced in 5% and the percentage of G3 AEs maintained in 0%. Conclusions: This improvement approach indicates the need to continue further quality projects in healthcare. Broader participation of Spanish hospitals in improvement initiatives will enhance the goal of a quality-oriented health care system.
Oral chemotherapy follow up on a Brazilian private health care unit.
Authors: Zukin Mauro , Soares Marcos Coelho Simões Travassos , Gamboa Nathalia Fonseca , Pombo Fabiano Hosken , Carvalho Lucyana
Published: May 2019

e18311

Background: Oral antineoplastic therapy is a growing reality, and ensures greater comfort and better quality of life for patients. However, this modality of treatment requires greater attention of the professionals to avoid dispensing errors and to guarantee adherence to the treatment. The goal of this study is to present a method to follow up cancer patients to reduce percentage of problems related to medication and improve oral antineoplastic adherence. Methods: The study was conducted at a private oncology clinic in Rio de Janeiro during the year 2018. In the first dispensation, patients received verbal and written pharmaceutical advice on posology, proper storage, safe handling requirements and strategies to avoid adverse side effects and food and drugs interactions. There were also given nutrition, sexuality, rights and duties guidelines. To improve adherence and to avoid forgetfulness or duplicity of dosing, patients received a medication calendar. Pharmacist made dispensing, managed adverse side effects and assessed adherence of patient using a model based on Morisky Medication Adherence Scale. Patients that answered "yes" to any questions were considered non-adherents. All information was registered in medical record. Non-compliances were considered: wrong medicine, incorrect dose and delays of any administrative reason. Results: In 2018, on average 1487 dispensings were made and 1053 patients’ adherence behavior were measured. 94.37% were considered adherent. Monthly percentage of non-compliance was 1.5% of dispensings. Conclusions: The present study demonstrates that with education and pharmaceutical follow-up since the first dispensation, it is possible to guarantee a safer and more effective treatment for patients using oral cancer medication. It is imperative to maintain the objective of developing better techniques for dispensing, guiding and guaranteeing high adherence.
NCI and ASCO CancerLinQ collaboration to advance quality of cancer care and surveillance.
Authors: Rivera Donna , Rubinstein Wendy S. , Schussler Nicola C. , Charlton Mary E. , Coyle Linda , Cronin Kathleen A , Howe Will , Kolacevski Andrej , Komatsoulis George Anthony , Lynch Charles F , Negoita Serban , Miller Robert S. , Penberthy Lynne
Published: May 2019

e18317

Background: The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program curates population-based cancer data representing 34% of the US population. CancerLinQ is an ASCO initiative that collects and analyzes electronic health record (EHR) data to give oncologists opportunities to improve the quality of patient care. With the shared goal of understanding care delivery, NCI SEER and CancerLinQ launched a pilot linkage. Purpose: Establish data exchange between registries and oncology practices to a) provide clinicians with SEER data to more effectively evaluate care within their practices, and b) enhance ability of SEER registries to capture cancer-related data and facilitate compliance of legally mandated public health reporting requirements while supporting metrics for quality reporting to providers. Methods: The SEER Iowa Cancer Registry is developing bidirectional linkages with CancerLinQ practices. The initial pilot in Iowa establishes connectivity and a data pipeline to capture discrete data elements in EHRs. The linkage methods are securely conducted by IMS, an honest broker for the Registry and ASCO. Patterns of care will be evaluated in the matched patient population. Analysis of shared data elements will provide comparative validation of data captured electronically (EHR) and manually (abstraction). Enhancing the patient care quality through efficient utilization of shared data was paramount when selecting treatment-related Quality Oncology Practice Initiative (QOPI) measures for calculation focusing on breast (QPP 449, QPP 450) and prostate cancer (QPP 102, QPP 104). Results: Publicly available SEER data for cohort evaluation is available to providers via SEERLinQ. The two-way exchange data pipeline complies with reporting requirements. Validation of shared data elements, statistics for matched patients, improved data completeness measures, and automated calculation of QOPI measures will be demonstrated. Conclusions: This collaboration builds an initial foundation of curated Registry-EHR linked data to automate cancer reporting to lower the physician burden, improve SEER evaluation of clinical care patterns, and enhance patient care quality.
What do doctors value about attending multi-disciplinary cancer case discussions?
Authors: Mitchell Paul , Soon Jennifer , Kenny Joanne , Simons Katherine
Published: May 2019

e18324

Background: Discussion of cancer cases at multi-disciplinary meetings (MDMs) for treatment planning is expected standard care in Australia. There has been rapid uptake of MDMs in the last 10 - 15 years and in the state of Victoria approximately 70% of cancer cases are discussed. MDMs have strong support from medical staff and we investigated their motivation in attending MDMs. Methods: Over 12 months, Austin Health in Melbourne, Victoria, hosted 452 cancer MDMs discussing 5943 patients. MDMs covered 15 tumour areas: 11 solid tumour, one lymphoma and three haematological. Over a 4-week period, medical staff attending MDMs were surveyed and asked to rank what they valued most about cancer MDMs, over and above the benefits for patients. Results: Responses were received from 84% of the 285 medical staff surveyed, which included consultants as well as trainees (registrars and fellows). For 75% of respondents the highest ranking was given to multi-disciplinary communication, 9% gave the highest ranking to quality assurance and governance, 5% ongoing learning for consultants, 5% collegiate relationships, 2% learning and teaching for non-consultant staff, 2% peer support 1% job satisfaction and 1% clinical trials engagement. Similar results were obtained for consultant staff and for registrars / fellows. For consultant medical staff, if multidisciplinary communication was excluded, 44% of respondents gave the highest ranking to quality assurance and governance, 23% to collegiate relationships, 20% ongoing learning for consultants, 10% peer support and 3% clinical trials engagement. Conclusions: When we asked doctors what they valued most about attending cancer MDMs, besides the benefits for patients, communication between disciplines was clearly the most valued aspect. The benefits for quality and governance was the next most valued, then collegiate relationships and peer support, and ongoing learning.
Diagnostic utility of tele-cystoscopy for bladder cancer surveillance.
Authors: Beller Haerin Lee , Mills James , Mason Jennifer , Horton Bethany J. , Jones Randy A. , Corey Thomas , Sims Terran , Schenkman Noah S. , Krupski Tracey Lynn
Published: May 2019

e18335

Background: Urology workforce shortage in rural areas limits access to surveillance cystoscopy for bladder cancer. Tele-cystoscopy is a novel solution whereby an advanced practice provider (APP) performs cystoscopy at a satellite location with real-time interpretation and guidance by an off-site urologist via transmitted video. We hypothesized that tele-cystoscopy videos would be comparable to traditional cystoscopy videos in diagnostic utility. Methods: Our IRB approved tele-cystoscopy protocol utilizes a dual-cystoscopy model. Two sequential cystoscopies are performed first by an APP with off-site urologist guidance (tele-cystoscopy) then by a urologist onsite (traditional cystoscopy) without removal of the cystoscope from the urethra. Both cystoscopies are video-captured. Twelve de-identified videos were reviewed via electronic survey (Qualtrics) by board-certified urologists who were blinded as to whom performed the cystoscopy. Survey questions centered on completeness of exam and diagnostic level of suspicion. A random effects logistic regression model was used to account for multiple reviews of the same video. Results: Diagnostic utility, defined as visibility sufficient for diagnosis, was 83% for both tele-cystoscopy and traditional cystoscopy. There were no statistically significant differences in completeness of exam between the two techniques (tele 83.3%, traditional 91.7%, p = 0.308). When asked about action taken based on cystoscopic findings, reviewers recommended action other than planned surveillance (i.e., biopsy, operative resection, etc.) for 58.3% of tele-cystoscopy videos vs. 66.7% for traditional cystoscopy videos (p = 0.300). Conclusions: Tele-cystoscopy provides high quality bladder surveillance with diagnostic capacity comparable to that of traditional cystoscopy. These results support continued expansion of the tele-cystoscopy platform as a means to amplify the care provided by a single urologist. [Table: see text]
Fear of receiving less effective care: A barrier to effective cancer care cost communication.
Authors: Kang Sokbom , Yu Yelee
Published: May 2019

e18339

Background: Increasing financial burden in cancer care promoted cost communication as an intervention to the problem. We explored patients’ attitudes and concerns for the physician-patient communication of the costs of cancer care. Methods: From an oncology outpatient clinic, patients were recruited and interviewed using a 29-item questionnaire. The questionnaire includes basic and financial characteristics, attitudes toward cost-communication, and experience of cost-communication with oncologists. Results: Among 292 patients with gynecologic cancer, 68% were found to have an income below the nation’s average households income. Although the majority (81%) of patients have a positive attitude toward patient-physician cancer care cost-communication, however, only 19% of them wanted to discuss the cost with their physicians - 33% of them did not want to disclose their financial status to health care providers and 48% wanted to discuss the cost with other providers than their physicians. In addition, while 87% preferred to be informed about costs for various treatment options, 86% of them did not want to receive cost-effective treatment and preferred to receive the most effective treatment regardless of their financial status. Compared with non-cancer patients (n = 83), significantly more patients had a negative attitude to disclosing their financial status especially to their physician (22% vs. 11%, P = 0.024). Conclusions: A considerable proportion of cancer patients had concerns that cost communication with their physician may interfere with their opportunity to access the best care options. To facilitate cost communication, oncologists should understand such concerns and making a thoughtful effort to relieve the concern during cost communication.
Treatment patterns, survival rate, and Parts A and B costs by line of therapy for FDA-approved/NCCN Category 1 treatments for patients with metastatic pancreatic cancer.
Authors: Muldoon L. Daniel , Hirsch Jared , Dieguez Gabriela , Cockrum Paul
Published: May 2019

e18357

Background: There is currently limited real-world evidence regarding metastatic pancreatic cancer (m-PANC) FDA-approved/NCCN Category 1 treatment patterns, resource utilization, and survival rate. We analyzed these outcomes in the Medicare fee-for-service (FFS) population by chemotherapy regimen and line of therapy (LOT). Methods: We identified patients with m-PANC using ICD-9/10 diagnosis codes in the 2013-2017 Medicare 100% Limited Data Set claims, which include all Medicare paid FFS claims, except professional services, for 45 million Medicare FFS beneficiaries. We studied mean costs and survival rate by regimen and LOT. Patients in our study had two or more claims with a pancreatic cancer (PANC) diagnosis more than 30 days apart and one or more claims with a secondary malignancy (metastasis) diagnosis on or after the first PANC diagnosis date. We defined index date as the earliest metastasis diagnosis date. We excluded patients with pre-index non-PANC malignancies and those without six months pre-index and three months (or until death, if earlier) post-index Medicare FFS enrollment. LOTs were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. Results: Gemcitabine monotherapy, gemcitabine/nab-paclitaxel, and FOLFIRINOX were most commonly used as first line (1L) therapy (91%, 80%, and 80%, respectively). Mean total Parts A and B (excluding professional) cost for 1L gemcitabine monotherapy was lower than gemcitabine/nab-paclitaxel or FOLFIRINOX ($14,601, $32,447, and $33,628, respectively), but FOLFIRINOX had a higher 90-day survival rate (86%) than gemcitabine-based regimens (76-79%). Liposomal irinotecan was most commonly used in second and third lines (2L, 3L) (54% and 28%, respectively); 97% of these patients previously received gemcitabine, consistent with approved labeling. Despite disease progression, 2L and 3L liposomal irinotecan had similar costs ($36,350 and $35,010, respectively) to 1L gemcitabine/nab-paclitaxel and FOLFIRINOX. As expected, 2L and 3L liposomal irinotecan 90-day survival rates were lower (68% and 73%, respectively). Conclusions: Mean total Parts A and B (excluding professional) costs for common 1L-3L regimens varied from less than $15,000 to greater than $30,000. 90-day survival rates for common regimens varied between 1L (86%) to 3L (68%).
Predictors of financial toxicity among head and neck cancer patients: A prospective cohort study.
Authors: de Almeida John R. , Hueniken Katrina , Eng Lawson , Giuliani Meredith , Ringash Jolie , Hansen Aaron Richard , Liu Geoffrey , Xu Wei , Li Madeline , Goldstein David Paul
Published: May 2019

e18361

Background: Treatment of Head and Neck Cancer (HNC) is associated with significant costs and treatment morbidity. The impact of treatment on financial well-being has not been investigated. Methods: Patients with HNC treated at Princess Margaret Cancer Centre, Canada between 2014 and 2018 were enrolled in a longitudinal study from treatment up to 24 months of follow up. Participants completed questionnaires for demographics, out-of-pocket cost during treatment and at 3, 6, 12, 24 months, and the Financial Toxicity Index (FTI) at 12 and 24 months. The FTI is a 14 item, Likert response scale, with summary score out of 14, and higher scores indicating greater toxicity. Preliminary reliability, validity, and responsiveness for the FTI are very good and ongoing. Uni- and multi-variable analyses (UVA, MVA) were performed to identify predictors for FTI score. Results: Among 363 patients enrolled, average age was 61, 76% male, 81% Caucasian, 72% married, 84% living with others, 53% at least college educated, 57% currently unemployed and 59% had stage IV disease. Median pre-treatment household income was $85K, median lost household income was $15K over 12 months following treatment. At least some difficulty paying for food (14%), housing (17%), or medications (11%) was experienced; 13% had to borrow money and 5% had to relocate housing due to financial pressures. Predictors of greater FTI scores on MVA were younger age (p < 0.001), living alone (p = 0.009), and lower baseline household income (p < 0.001). In subgroup analysis of patients with available information, lost household income (p < 0.001) but not out of pocket costs (p = 0.58) was associated with higher FTI score. Conclusions: Financial toxicity is not uncommon in patients with HNC. Younger age, lower baseline income, living alone, and loss of household income are associated with financial toxicity. This should be a priority population for research into improved supportive care and return to work strategies.
Economic impact of post-progression treatment in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients previously treated with octreotide monotherapy.
Authors: Ray David , Zivkovic Marko , Gargano Michael , Soares Heloisa P.
Published: May 2019

e18366

Background: For unresectable, well-differentiated, advanced GEP-NET patients somatostatin analogs octreotide LAR (OCT) and lanreotide depot (LAN) are recommended as first-line systemic therapy. Recent evidence suggests that GEP-NET patients may benefit from LAN after OCT prior to modifying treatment class. The goal of this analysis is to quantify treatment escalation costs among patients who progress on OCT. Methods: A decision-tree model was used to assess the cost of treating GEP-NET patients over a 6-month time horizon after they progress on OCT. Drug acquisition (Wholesale Acquisition Costs), administration, grade 3/4 adverse event (AE) management, and patient monitoring costs were considered. Patients could utilize either OCT escalation (30 mg every 3 weeks or 40 or 60 mg every 4 weeks), OCT + peptide receptor radionuclide therapy (PRRT), OCT + liver directed therapy (e.g. transarterial chemoembolization (TACE)), everolimus, or LAN 120mg every 4 weeks. Administration and monitoring test costs were based on CMS physician and laboratory fee schedules, respectively. AE management costs were determined from the CMS Inpatient prospective payment system based on reimbursements corresponding to the associated DRG codes. Results: LAN ($44,462) was found to be cost-saving versus alternatives when used post-OCT. OCT escalations to 30mg every 3 weeks, 40mg every 4 weeks, and its use with liver directed therapy were 2nd, 3rd, and 4th lowest cost treatment options ($52,873, $53,041, and $72,152, respectively); all three had higher drug acquisition and AE management costs. Drug acquisition costs for everolimus were more than twice those of LAN and for PRRT + OCT nearly 4 times that amount. GA-68 Dotatate PET/CT imaging greatly increased the monitoring costs of PRRT + OCT, which were $3,682 higher than the nearest alternative. Conclusions: LAN was the lowest cost treatment option over a 6-month interval for GEP-NET patients who progressed on OCT, however clinical appropriateness must be considered when transitioning patients. Evidence for the appropriate clinical strategy of sequencing of patients is still needed.
A novel algorithm to redefine blood-based tumor mutational burden for optimized prediction of clinical benefits from immunotherapy.
Authors: Wang Zhijie , Wang Guoqiang , Duan Jianchun , Zhao Jing , Zhao Zhengyi , Bai Hua , Wang Shuhang , Cai Shangli , Wang Jie
Published: May 2019

e20514

Background: The previous reported predictive biomarker, blood-based tumor mutational burden (bTMB) can only predict progression-free survival (PFS) while failed to predict overall survival (OS) from atezolizumab over docetaxel, or to predict PFS or OS in the atezolizumab arm. Here we aimed to explore the underlying mechanism and develop an algorithm to redefine bTMB as a predictor of both PFS and OS from immunotherapy. Methods: Data from POPLAR (N = 211) and OAK (N = 642) trials was used for algorithm development in bTMB redefinition. The derived algorithm was validated in two independent NSCLC cohorts (cohort 1 N = 64; cohort 2 N = 184). Results: In POPLAR and OAK cohorts, bTMB-H was not associated with favorable OS (P = 0.68, HR 1.06; 95% CI, 0.81-1.38) from immunotherapy at the reported cut-point of 16, which was validated in our independent cohort 1 (P = 0.86, HR 0.39; 95% CI, 0.39-1.89). Further analysis showed that blood TMB was associated with maximum somatic allele frequency (Pearson r = 0.47 in POPLAR and OAK cohorts, Pearson r = 0.36 in the independent cohort 2), which was a negative prognostic factor and may impede the predictive value of bTMB. The bTMB was thus redefined (referred to as bTMB*) with mutations with allele frequency > 5% filtered out, when the correlation between bTMB and MSAF became less correlated (Pearson r = 0.09 and 0.07, respectively). Both better PFS and OS benefits from atezolizumab over docetaxel was observed in the redefined bTMB-H group as tested in POPLAR (PFS HR = 0.41, 95% CI, 0.21-0.80; OS HR = 0.34, 95% CI, 0.16-0.71) and validated in OAK (PFS HR = 0.49, 95% CI, 0.33-0.71; OS HR = 0.47, 95% CI, 0.29-0.77) with the cut-point of 12, while there was no significant association in redefined bTMB-L group (P interaction = 0.01 and 0.04 for PFS and OS in POPALR, < 0.001 and 0.06 for OAK PFS and OS in OAK). The results was further validated in our independent cohort 1 treated with anti-PD-1/PD-L1, where the redefined bTMB-H was also associated with favorable PFS compared with bTMB-L (Logrank P = 0.005, HR = 0.34, 95% CI, 0.26-0.75) and OS (Logrank P = 0.08, HR 0.35, 95% CI, 0.11-1.18). Conclusions: The allele frequency needs to be taken into consideration in the algorithm of bTMB. The redefined bTMB may serve as a predictor of both PFS and OS of immunotherapy.
The efficacy and safety of extended use of endostatin plus platinum-based doublet chemotherapy in patients with advanced non-small cell lung cancer: An analysis of a 10-year retrospective study.
Authors: Zhao Jing , Wang Jianhua , Zhao Xueqi , Cheng Yi , Xi Qingsong , Mei Qi , Hu Guangyuan
Published: May 2019

e20523

Background: Endostatin is a potent inhibitor of angiogenesis developed and approved in China. We aimed to evaluated the efficacy and safety of extended use of endostatin with platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC) in this study. Methods: We performed a retrospective analysis of chemotherapy-naïve patient with stage IIIB-IV or recurrent NSCLC who had been treated with first-line chemotherapy plus endostatin between January 2008 and June 2018. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The Cox proportional hazards regression model was used to assess the prognostic importance of risk factors (age, gender, smoking status, ECOG performance status, stage, histology, EGFR gene status and endostatin cycles). Results: A total of 105 patients were eligible for analysis. The median (range) cycles of chemotherapy with endostatin were 4 (2-19). The objective response rate and disease control rate were 45.1% and 87.3%, respectively. Under multivariate analysis, non-smoking status and extended use of endostatin (≥4 cycles) were significantly correlated with better PFS, and squamous cell cancer and extended use of endostatin (≥4 cycles) were significantly correlated with better OS. The median (95% CI) PFS and OS for patients with extended use of endostatin (≥4 cycles) or not were 8.2 (5.6-12.7) vs. 5.3 (2.8-7.3) months, HR = 0.63, p= 0.014, and 21.2 (6.8-37.7) vs. 11.9 (4.1-23.9) months, HR = 0.77, p= 0.028, respectively. Patients with squamous cell cancers significantly benefited from the extended use of endostatin (≥4 cycles) (n = 55, p= 0.043) but not adenocarcinoma (n = 46, p= 0.089). Hematologic and gastrointestinal toxicities occurred more frequently in patients who received extended use of endostatin (≥4 cycles), but no statistically significant difference was detected in those who did not. Conclusions: In patients with advanced/recurrent NSCLC, extended use of endostatin (≥4 cycles) could provide additional survival benefits and satisfactory toxicity profiles, especially for those with squamous cell cancer, which merits further evaluation in a larger prospective study.
Rebiopsy in patients with or without prior TKIs revealed complicated histology of lung cancer.
Authors: Zhu Kuikui , Li Qianwen , Zhang Sheng , Wu Gang , Xiang Qun , Fang Zhili , Meng Rui
Published: May 2019

e20525

Background: The important of rebiopsy is well known in lung adenocarcinomas (ADs) after acquiring resistant to TKIs, for they may transform to SCLC. But histology transformation in non-ADs or ADs without TKIs seems infrequent. Methods: We performed a retrospective collection of cases with changed histology after rebiopsy in patients presenting from January 2015 to April 2018 in a single center. Results: Among 188 patients who conducted rebiopsy, there were 20 cases presenting changed histologic type, which can be divided into two groups based on if TKIs were used before histology change. Group1 (TKIs used, N = 14) including ADs changing to SCLC (N = 9), squamous cell carcinoma (SQ) (N = 2), carcinosarcoma combined with few AD component (N = 1), SCLC combined AD (N = 1), and adenosquamous carcinoma changing to SCLC (N = 1). Four cases in group 1 went through surgery, and one of them who never smoke was diagnosed as AD (pT2N0M1a, EGFR exon 19del), with no small cell carcinoma (SCC) component found, but rebiopsy of metastasis revealed SCC without any AD component after 3 months of gefitinib. The disease continued to progress during the following chemotherapy (CT), and biopsies with other two metastases also presented SCC without AD component. Group 2 were 6 cases without TKIs before the rebiopsy (Table). Case 2, 4, 6 were all heavy smokers. Rebiopsy of case 2 was ALK+, so the patient took 4 months crizotinib and then 2 months alectinib, the disease was still stable on January 6, 2019. Case 5 was a classic extensive-stage SCLC with fast response to EP therapy, but fast relapse and resistance to the following CT, and the primary lesion at right upper lobe showed AD-like imaging, so rebiopsy was performed and carcinoma favor AD was found. EGFR exon 19del was detected in the plasma, and the lesion gain PR after one month of icotinib. The third biopsy of the progress lesion came back to SCC after resistance to TKI. Conclusions: Rebiopsy of lung cancers with or without TKIs therapy revealed diversity histology changes. This reminded us the important of rebiopsy, not only for TKIs resistant lung ADs. [Table: see text]
Myeloid immunosuppressive state as a predictor of rapidly progressive phenotype and poor survival in advanced non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors.
Authors: Lau Sally CM , Le Lisa W , Chan Sze Wah Samuel , Smith Elliot Charles , Ryan Malcolm , Brown M. Catherine , Hueniken Katrina , Eng Lawson , Patel Devalben , Chen RuiQi , Zer Alona , Sung Mike Ru , Bradbury Penelope Ann , Ohashi Pamela S , Shepherd Frances A. , Tsao Ming Sound , Leighl Natasha B. , Liu Geoffrey , Sacher Adrian G.
Published: May 2019

e20594

Background: Immune subpopulations within the tumor microenvironment (TME) play a central role in determining response to checkpoint inhibitors. Myeloid derived suppressor cells, a heterogeneous population of immature myeloid cells, have a predominantly immunosuppressive role by stimulating T regulatory cells. We hypothesize that elevated myeloid-to-lymphocyte measures in the peripheral blood predict for greater numbers of myeloid derived suppressor cells in the TME and worse outcomes. Methods: In advanced NSCLC patients who received immunotherapy between 2010-2018, baseline characteristics collected retrospectively included age, sex, histology, stage, smoking status, ethnicity, PD-L1 expression and tumor genotype. Pre-treatment neutrophil/lymphocyte (NLR) and monocyte/lymphocyte ratios (MLR) were log transformed and analyzed using cox and logistic regression models. Results: Among 219 eligible patients, a high NLR was associated with shorter time-to-treatment-failure (HR 1.38, 95%CI 1.09-1.75, p = 0.008) and poorer OS (HR 1.62, 95%CI 1.23-2.14, p < 0.001), independent of PD-L1 levels. Disproportionate increases in NLR and MLR were highly correlated (Spearman’s rho = 0.78). Further, higher NLR (p = 0.09) or MLR (p = 0.06) tended to associate with best overall response (BOR) to immunotherapy, with higher rates of progressive disease (PD) and lower rates of clinical response. A high NLR (p = 0.01) and MLR (p = 0.02) were associated with a rapidly progressive phenotype defined by PD as the BOR and duration of therapy ≤2 months. This remained significant after adjusting for confounders in a multivariate model (p = 0.03 for NLR and p = 0.03 for MLR). No associations were observed between high myeloid counts and other clinical prognostic factors such as liver metastases. Conclusions: A myeloid immunosuppressive state characterized by a disproportionate increase in peripheral immune myeloid populations is significantly associated with primary refractory disease, rapidly progressive phenotype, and poorer survival. Further investigation into myeloid mediated mechanisms of resistance is warranted.
Development and validation of a deep learning model to assess tumor progression to immunotherapy.
Authors: Yang Yi , Yang Jiancheng , Ye Yuxiang , Xia Tian , Lu Shun
Published: May 2019

e20601

Background: Manual application of length-based tumor response criteria is the standard-of-care for assessing metastatic tumor response. It is technically challenging, time-consuming and associated with low reproducibility. In this study, we presented a novel automatic Deep Neural Networks (DNNs) based segmentation method for assessing tumor progression to immunotherapy. Next stage, AI will assist Physicians assessing pseudo-progression. Methods: A data set of 39 lung cancer patients with 156 computed tomography (CT) scans was used for model training and validation. A 3D segmentation DNN DenseSharp, was trained with an input size of on CT scans of tumor with manual delineated volume of interest (VOI) as ground truth. The trained model was subsequently used to estimate the volumes of target lesions via 16 sliding windows. We referred the progression-free survival (PFS) only considering tumor size as PFS-T. PFS-Ts assessed by longest tumor diameter (PFS-Tdiam), by tumor volume (PFS-Tvol), and by predicted tumor volume (PFS-Tpred-vol) were compared with standard PFS (as assessed by one junior and one senior clinician). Tumor progression was defined as > 20% increase in the longest tumor diameter or > 50% increase in tumor volume. Effective treatment was defined as a PFS of > 60 days after immunotherapy. Results: In a 4-fold cross-validation test, the DenseSharp segmentation neural network achieved a mean per-class intersection over union (mIoU) of 80.1%. The effectiveness rates of immunotherapy assessed using PFS-Tdiam (32 / 39, 82.1%), PFS-Tvol (33/39, 84.6%) and PFS-T pred-vol (32/39, 82.1%) were the same as standard PFS. The agreement between PFS-Tvol, and PFS-Tpred-vol was 97.4% (38/39). Evaluation time with deep learning model implemented with PyTorch 0.4.1 on GTX 1080 GPU was hundred-fold faster than manual evaluation (1.42s vs. 5-10 min per patient). Conclusions: In this study, DNN based model demonstrated fast and stable performance for tumor progression evaluation. Automatic volumetric measurement of tumor lesion enabled by deep learning provides the potential for a more efficient, objective and sensitive measurement than linear measurement by clinicians.
Clinical implications of monitoring circulating tumor DNA in early- and late-stage non-small cell lung cancer patients.
Authors: Peng Muyun , Chin Lihan , Huang Qi , Yin Wei , Tan Sichuang , Chen Chen , Liu Wenliang , Tang Jingqun , Wang Xiang , Wang Lientu , Yu Fenglei
Published: May 2019

e20607

Background: Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the most common types of NSCLC are squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. The development of noninvasive methods to monitor circulating tumor DNA (ctDNA) continues to be a major challenge in NSCLC. Methods: We investigated if detection of ctDNA after resection of NSCLC identifies the patients with risk of relapse, and furthermore, informs about response to management.In this cohort study, high-throughput 168 target-gene capture technology and high-sensitivity circulating single molecule amplification and re-sequencing technology (cSMART) were used to detect the somatic mutations in tissues and plasma of patients with NSCLC, respectively. Moreover, ctDNA somatic mutations were used to monitor changes in minimal residual disease during a follow-up period. Results: A total of 169 patients with lung squamous cell carcinoma and adenocarcinoma were included. Detectable levels of ctDNA were present in 60.7% of patients with stage I and 68.8% of patients with late-stage. In patients not treated with adjuvant chemotherapy, ctDNA was detected preoperatively in 46 of 81 (56.8%) patients, 14 (30.4%) of whom had recurred at follow-up of 44 months; recurrence occurred in only 2 (5.7 %) of 35 patients with negative ctDNA. Serial ctDNA status changed from positive to negative during the initial phase of post operation in four patients. Then, ctDNA became positive again after 2 weeks to 3 months, all the four patients with relapse during the follow-up of 44 months. Conclusions: Detection of ctDNA supplies evidence of residual disease and identifies patients at risk of relapse. These observations have implications for the intervention of lung squamous cell carcinoma and adenocarcinoma patients.
Activity of osimetrinib/AZD9291 in pretreated patients (pts) with epidermal growth factor receptor mutant (EGFRmt) non-small cell lung cancer (NSCLC), according to EGFR mutations detected in circulating plasma DNA (ctDNA).
Authors: Kontopodis Emmanouil , Nuria Jordana , Ntzifa Aliki , Katsaounis Panayiotis , Charalambous Charalambos Haris , Boukovinas Ioannis , Tsaroucha Emily , Psyrri Amanda , Koumarianou Anna , Nikolaou Michail , Kentepozidis Nikolaos K. , Rosell Rafael , Georgoulias Vassilis , Karachaliou Niki , Kotsakis Athanasios
Published: May 2019

e20608

Background: Osimertinib is an irreversible EGFR tyrosine kinase inhibitor (TKI), selective for EGFR TKI-sensitizing mutations and the T790M resistance mutation. We sought to determine the activity of osimertinib after progression on EGFR TKIs in pts with T790-negative ctDNA. Methods: A multicenter phase II study ( clinicaltrials.gov NCT02771314) of osimertinib (80 mg daily) was conducted in pts with metastatic EGFRmt NSCLC, who had progressed after previous treatment with EGFR TKIs. Serial serum and/or plasma samples were drawn for ctDNA analysis at enrollment, 1 month and every 3 months of treatment, until disease progression. Efficacy outcomes in pts without the T790M mutation in ctDNA at baseline are reported. Results: Thirty-seven NSCLC patients with undetectable baseline T790M in the plasma have been enrolled. Median age was 67 years, 21.6% were male, and histology was adenocarcinoma in 100%. More frequent adverse events (grade 1/2) included diarrhea (12.5%), fatigue (12.5%), anorexia (12.5%) and acneiform rash (10.4%). The overall response rate (ORR) was 40.5% (95% CI, 24.7-56.4%) and the disease stabilization rate 37.8%; the median progression-free survival (PFS) was 8.9 months (range, 1.6-30), and the estimated median overall survival (OS) 26 months (range, 2.2-30). At enrollment, EGFR mutations del19 and L858R were detected in ctDNA in 9 and 3 pts, respectively. After one month of treatment with osimertinib, EGFR mutations in ctDNA were not detectable in 4/9 and 2/3 of pts with del19 and L858R at baseline, respectively. Pts without detectable EGFRm ctDNA at baseline remained negative throughout the study. Efficacy according to baseline ctDNA status was as follows: Clinical trial information: NCT02771314. Conclusions: Osimertinib was effective in EGFR TKI pretreated pts without EGFR T790M mutation in plasma. Pts with detectable del19 or L858R mutations in ctDNA before treatment had worse clinical outcomes, despite the elimination of EGFRmt ctDNA.[Table: see text]
Early clinical experience with the pan-FGFR inhibitor rogaratinib in patients with non-small cell lung cancer selected based on FGFR mRNA expression levels.
Authors: Joerger Markus , Cho Byoung Chul , Mach Nicolas , Caballero Cristina , Soo Ross A. , Wirth Manfred , Sayehli Cyrus , Navarro Alejandro , Keam Bhumsuk , Piciu Ana-Maria , Bender Sebastian , Nogai Hendrik , Ellinghaus Peter , Schuler Martin H.
Published: May 2019

e20661

Background: FGFR1 gene amplifications are observed in squamous (sq) non-small cell lung cancer (NSCLC) and may suggest tractable oncogenic dependency. However, their value in predicting clinical activity of FGFR inhibitors is unclear. We explored tumor FGFR1-3 mRNA expression levels to select patients (pts) for treatment with rogaratinib, an oral, potent, small-molecule inhibitor of FGFR1-4. The first-in-human study of rogaratinib included pts with all NSCLC histologies. Methods: Pts with refractory advanced NSCLC were screened for elevated FGFR1-3 mRNA levels by RNA in situ hybridization (RNAscope) and NanoString assay in fresh or archival tumor samples, and FGFR1-3 overexpression was defined by pre-specified cut-offs. Pts received rogaratinib 800 mg BID on a continuous 21-day cycle. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.1 after cycles 2, 5, and 8. Results: 260 NSCLC biopsies were screened for FGFR1-3 tumor mRNA expression; 244 (93.8%) were evaluable. FGFR1-3 mRNA overexpression was found in 47% of sq NSCLC, and only 14% of non-sq NSCLC, with FGFR3 being the most commonly overexpressed subtype. 40 FGFR mRNA-positive pts were enrolled and treated. Rogaratinib was well tolerated; hyperphosphatemia (75%), diarrhea (53%), and decreased appetite (35%) were the most frequent treatment-emergent adverse events. Events were mostly mild or moderate. 36 treated pts were evaluable for response. The overall response rate was 5.6% (2 partial responses, 1 lasting for > 16 months). Disease control rate was 64%. Disease stabilization was seen in pts with mRNA overexpression across all FGFR subtypes and also in pts who failed prior lines of therapy, including anti-PD-L1. Molecular studies are ongoing to identify additional predictors of response to improve pt selection. Conclusions: Rogaratinib has a favorable safety and tolerability profile and clinical activity in pts with refractory FGFR1-3 tumor mRNA-positive NSCLC. It has potential for further exploration in combination with other agents. A clinical trial is currently enrolling FGFR mRNA-overexpressing pts with advanced and pre-treated sq NSCLC. Clinical trial information: NCT03762122.
Bone metastases as predictors of treatment response and rapidly progressive disease in NSCLC patients on PD-1/PD-L1 immune checkpoint inhibitors (ICI).
Authors: Lau Sally CM , Le Lisa W , Smith Elliot Charles , Chan Sze Wah Samuel , Ryan Malcolm , Brown M. Catherine , Hueniken Katrina , Eng Lawson , Patel Devalben , Chen RuiQi , Sung Mike Ru , Zer Alona , Bradbury Penelope Ann , Ohashi Pamela S , Shepherd Frances A. , Tsao Ming Sound , Liu Geoffrey , Leighl Natasha B. , Sacher Adrian G.
Published: May 2019

e20667

Background: The tissue microenvironment associated with specific organ metastases potentially influences the efficacy of checkpoint inhibitors. The presence of liver metastases is a predictor of poor response and survival in melanoma and is correlated with reduced CD8+ T cell infiltration. Our study examined clinicopathologic characteristics, focusing on sites of metastatic disease, that are associated with poor outcomes. Methods: Advanced NSCLC patients treated with ≥1 cycle of ICI were reviewed. Baseline age, sex, histology, stage, smoking status, ethnicity, PD-L1 expression and sites of metastases were recorded. Best overall response (BOR) was determined by clinical imaging response and categorized ordinally as shrinkage, stable, or progression, adapted from RECIST for CR/PR, SD, PD. A rapidly progressive phenotype (RPP) was defined as BOR of progression and ICI use of ≤2 months. The association between sites of metastases and clinical outcomes were investigated using logistic and cox regression models. Results: Among 219 eligible patients, bone was the most common metastatic site (34.7%), followed by brain (21.5%), adrenals (14.2%), and liver (13.7%). Bone metastases (OR 0.45, p = 0.004) were associated with a worse BOR, while only a trend was observed for liver metastases (OR 0.47, p = 0.06). Adrenal metastases were associated with a better BOR (OR 2.08, p = 0.04). But thorax limited disease did not associate with BOR (OR 1.08, p = 0.76). In a multivariate model, bone was the only metastatic site associated with a worse BOR (OR 0.50, p = 0.01). Further, bone metastases were associated with RPP (adjusted OR 1.91, p = 0.04). Both bone (adjusted hazard ratio/aHR 1.61, p = 0.01) and liver metastases (aHR 1.80, p = 0.02) were associated with a shorter time-to-treatment-failure. The presence of liver (aHR 2.63, p < 0.001) but not bone (aHR 1.04, p = 0.86) metastases was a significant predictor of poor OS. Conclusions: We report a novel finding that the presence of bone metastases was associated with a worse clinical overall response on ICI and a rapidly progressive phenotype. Further investigations into the mechanisms of RPP in the presence of bone metastases are needed.
Real-world clinical and economic outcomes among newly-diagnosed merkel cell carcinoma (MCC) patients initiating first-line (1L) checkpoint inhibitors (CPIs) or chemotherapy (CT) in the veterans health administration (VHA).
Authors: Phatak Hemant , Pandya Shivani , Yu Ting , Kearney Mairead , Wang Li , Kim Ruth , Zheng Ying
Published: May 2019

e21002

Background: The use of CPIs among patients (pts) with metastatic MCC, a rare and aggressive skin cancer, has increased since the US FDA approval of avelumab and the National Cancer Comprehensive Network (NCCN) recommendation of CPIs in 2017. Given the growing interest in understanding real-world clinical and economic outcomes associated with CPI use, this study assessed time to treatment failure (TTF), overall survival (OS), healthcare resource utilization (HRU), and costs among MCC pts receiving NCCN-recommended 1L regimens including CPIs and CT in the VHA. Methods: This is a retrospective analysis of pts with newly-diagnosed MCC who initiated 1L treatment between October 2013 and January 2018 (index date = 1L therapy start date) and had continuous enrollment from ≥6 months pre-initial MCC diagnosis date until ≥2 months post-index date (follow-up). The index date to earliest of death or subsequent line of therapy start was used as a proxy for TTF. TTF and OS were estimated using Kaplan Meier method. All-cause HRU and costs (2018 USD) per patient per month (PPPM) were evaluated during TTF or until end of follow-up, whichever occurred first. Results: Of 120 MCC pts (72% pre-2017) initiating 1L therapy, 62% received NCCN-recommended regimens, including 17% and 45% treated with CPIs and CTs. Pts receiving CPIs were on average older with higher baseline comorbidity burden. The clinical and economic outcomes of these two pt groups are summarized in the table below. Conclusions: The current descriptive non-comparative analyses provide new information on the trends in clinical and economic outcomes of MCC pts treated in the VHA. Despite higher costs, the utilization of newly-approved CPIs in 1L setting showed delayed treatment failure and reduced all-cause HRU vs. CTs. These findings require further validation in studies with larger patient cohorts and longer follow-up. [Table: see text]