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1.
Paola Morelato Assunção Tamires Prates Lana Márcia Torresan Delamain Gislaine Oliveira Duarte Roberto Zulli Irene Lorand-Metze Carmino Antonio de Souza Erich Vinicius de Paula Katia Borgia Barbosa Pagnano 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):162-166
Background
Cardiovascular events (CVEs) have been observed in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors.Patients and Methods
We retrospectively evaluated the incidence of CVEs on 233 consecutive patients with chronic myeloid leukemia, of which 116 were treated with imatinib, 75 with dasatinib, and 42 with nilotinib. The median follow-up was 2047, 1712, and 1773 days, respectively.Results
The cumulative incidence of CVEs was 4.29%. Three events occurred during dasatinib treatment, 6 during nilotinib treatment, and none during imatinib treatment (P ≤ .001). Arterial occlusive events occurred in 2 (2.6%) of 75 patients treated with dasatinib and in 6 (14.2%) of 42 patients treated with nilotinib (P ≤ .001). Furthermore, all of them occurred in patients with high-risk (n = 2) and very high-risk (n = 6) cardiovascular risk, contributing to 4.3% of mortality.Conclusion
CVEs were more frequent in patients treated with second-generation tyrosine kinase inhibitors. Arterial occlusive events were more frequent in patients treated with nilotinib, with high and very high cardiovascular risk. 相似文献2.
Bernardo Cacho-Díaz Héctor Spínola-Maroño Nancy Reynoso Alberto González-Aguilar Alejandro Mohar-Betancourt 《Clinical breast cancer》2019,19(2):e394-e398
Introduction
Breast cancer (BC) is the most common cancer in women, and the incidence of brain metastasis (BM) from BC ranges from 20% to 30%, with a median survival of 10 to 15 months. Previous reports have shown that the presence of obesity or diabetes negatively impacts survival. The present study investigates the association between obesity or diabetes mellitus (DM) and overall survival of patients with BC with BM.Materials and Methods
A database from 2 referral centers for the period of July 2014 to February 2018 was analyzed. The inclusion criteria were as follows: patients who had a confirmed diagnosis of BC with BM were followed and treated at these centers. Demographic data, body weight and height, clinical and oncologic history, functional status, prognostic scales, and prognoses were examined.Results
A total of 228 patients were included. The median age at BM was 50 years; the median survival after diagnosis was 12.1 months; 108 patients had a body mass index (BMI) ≥ 25, and 40 (17%) patients had DM. The association between survival and the presence of BMI > 25 exhibited a P value of 0.3.Discussion
We found no association between overweight, obesity, or DM and survival in patients with BC with BM. The role of obesity in cancer is a robust research topic, as there are many questions to be answered.Conclusion
Obesity as a prognostic indicator should be further studied, because we found no association between overall survival and either patients with BM from BC with a BMI > 25 or those with normal weight. 相似文献3.
Chao Zhang Shao-lei Li Qiang Nie Song Dong Yang Shao Xue-ning Yang Yi-long Wu Yue Yang Wen-zhao Zhong 《Journal of thoracic oncology》2019,14(4):726-731
Background
Locally advanced NSCLC is one of the most heterogeneous conditions, with multidimensional treatments involved. Neoadjuvant therapy had been commonly considered an optimal management strategy for patients with operable locally advanced. However, as targeted therapy has been widely applied in advanced NSCLC, neoadjuvant targeted therapy has remained poorly explored in locally advanced disease.Methods
We have described 11 ALK receptor tyrosine kinase gene (ALK)-positive patients with pathologically confirmed N2 NSCLC who were treated with neoadjuvant crizotinib. All the patients were treatment naive and received crizotinib at a starting dose of 250 mg twice daily. Patient 3 was provided with dynamic monitoring before and after neoadjuvant therapy through next-generation sequencing of plasma and tissue. In case 4, next-generation sequencing of preoperative tissue was performed.Results
Of the 11 patients, 10 had a partial response and one was stable disease after neoadjuvant crizotinib, with one suffering from grade 4 hepatic damage. Of the 11 patients, 10 (91.0%) received an R0 resection and 2 patients achieved a pathological complete response to neoadjuvant crizotinib. Six patients had disease recurrence, with five of them receiving crizotinib as first-line treatment and achieving a long duration of response. Dynamic monitoring of both plasma and tissue simultaneously indicated a decrease in sensitive ALK signaling in patient 3 and a partial response (approximately 50% of partial response), and no ALK-dependent resistance variants were captured.Conclusion
Neoadjuvant crizotinib may be feasible and well tolerated in locally advanced disease for complete resection. Crizotinib therapy before surgery may provide thorough elimination of circulating molecular residual disease and not influence the reuse of first-line crizotinib, but ongoing prospective trials are warranted to prove its efficacy in the neoadjuvant setting. 相似文献4.
Aabra Ahmed Ahmed Tahseen Elizabeth England Katrine Wolfe Michael Simhachalam Travis Homan Jenna Sitenga Ryan W. Walters Peter T. Silberstein 《Clinical colorectal cancer》2019,18(1):e1-e7
Background
Colon cancer is the third most frequent cancer diagnosis, and primary payer status has been shown to be associated with treatment modalities and survival in cancer patients. The goal of our study was to determine the between-insurance differences in survival in patients with clinical stage III colon cancer using data from the National Cancer Database (NCDB).Materials and Methods
We identified 130,998 patients with clinical stage III colon cancer in the NCDB diagnosed from 2004 to 2012. Kaplan-Meier curves and multivariable Cox regression models were used to determine the association between insurance status and survival.Results
Patients with private insurance plans were 28%, 30%, and 16% less likely to die than were uninsured patients, Medicaid recipients, and Medicare beneficiaries, respectively. Medicare patients were 14% were less likely to die compared with uninsured patients. Patients receiving chemotherapy were, on average, 65% less likely to die compared with the patients not receiving chemotherapy.Conclusion
Private insurance and a greater socioeconomic status were associated with increased patient survival compared with other insurance plans or the lack of insurance. Future research should continue to unravel how socioeconomic status and insurance status contribute to the quality of care and survival of oncologic patients. 相似文献5.
Sungwoo Park Jae-Cheol Jo Young Rok Do Deok-Hwan Yang Sung-Nam Lim Won-Sik Lee Won Seog Kim Ho Sup Lee Dae-Sik Hong Hyo Jung Kim Ho-Jin Shin 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):149-156
Introduction
Elderly patients are more prone to encounter some adverse factors when they receive chemotherapy compared to younger patients. Addition of rituximab to a reduced dose (RD) of cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy might improve patient outcomes with an improved toxicity profile when provided to elderly patients with diffuse large B-cell lymphoma.Patients and Methods
A total of 53 patients aged ≥ 65 years with diffuse large B-cell lymphoma diagnosed between August 2012 and December 2014 were enrolled onto this study. RD-R-CHOP regimen consisted of rituximab at 375 mg/m2, cyclophosphamide at 600 mg/m2, doxorubicin at 30 mg/m2, and vincristine at 1 mg on day 1 of each cycle and 40 mg of prednisone on days 1 to 5. Patients received granulocyte colony-stimulating factor if they experienced grade 3/4 neutropenia or febrile neutropenia during any cycle.Results
The median follow-up duration was 18 months (range, 1-44 months). Complete response and overall response rates were 64.1% and 81.1%, respectively. Three-year event-free and overall survival rates were 45.7% ± 8.4% and 62.7% ± 8.1%, respectively. Grade 3/4 neutropenia occurred in 20 patients (37.7%), while febrile neutropenia occurred in 7 patients (20.7%).Conclusion
Outcomes of RD-R-CHOP chemotherapy were comparable to those of standard-dose R-CHOP or previous dose-adjusted R-CHOP chemotherapy. In the future, strategies such as tailored therapy based on geriatric assessment results are needed to determine the chemotherapeutic dosage. 相似文献6.
Purpose
To assess the pharmacologic costs of second-line treatments for metastatic renal-cell cancer (mRCC).Methods
The present evaluation was restricted to pivotal phase 3 randomized controlled trials in second-line for mRCC. We calculated the pharmacologic costs necessary to get the benefit in progression-free survival and overall survival (OS) for each trial. The costs of drugs are at the pharmacy of our hospital and are expressed in euros.Results
Our analysis evaluated 5 phase 3 randomized controlled trials including 3112 patients. The lowest cost per month of progression-free survival and OS gained was associated with the use of cabozantinib (€2006 and €1473, respectively), while everolimus had the highest cost per month of OS gained (€28,590).Conclusion
Combining pharmacologic costs of drugs with the measure of efficacy represented by OS, cabozantinib is a cost-effective second-line treatments for patients with mRCC. 相似文献7.
S. Bergamin T. Eade A. Kneebone J.G. Kench P. Sved J.-F. Biset G. Hruby 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):108-114
Aims
Ductal adenocarcinoma is a rare variant of prostate cancer, and as such clinical outcomes and best management are not well defined. This series demonstrates the atypical presentation and unusual clinical behaviour of ductal adenocarcinoma and proposes management guidelines to assist clinicians.Materials and methods
A retrospective review of pure (nine patients) and mixed (18 patients) ductal adenocarcinoma of the prostate referred to the Departments of Radiation Oncology of the Sydney Cancer Centre, Royal Prince Alfred Hospital and Northern Sydney Cancer Centre, Royal North Shore Hospital, between 2000 and 2015.Results
Twenty-seven patients were treated with definitive radiotherapy, nine patients (33%) with pure ductal and 18 (67%) with mixed ductal-acinar adenocarcinoma. The median follow-up was 38 months. Four patients (15%) failed locally, all of whom received less than 80 Gy, or no brachytherapy boost. Five patients (19%) failed distantly, four with biopsy-proven lung metastases. All distant failures occurred with a prostate-specific antigen (PSA) < 3 ng/ml.Conclusion
This series shows the atypical clinical presentation of this entity, as well as its propensity to metastasise to unusual sites. Relapse may occur at low absolute PSA values and is often asymptomatic. Ductal cancer should not simply be regarded as a high Gleason grade cancer. We propose management guidelines, including regular computed tomography examinations (rather than relying solely on PSA levels) as part of the follow-up for patients with any component of ductal adenocarcinoma. 相似文献8.
Uday Yanamandra Prateek Deo Kamal Kant Sahu Ram Vasudevan Nampoothiri Nalini Gupta Anusree Prabhakaran Deb Prasad Dhibhar Alka Khadwal Gaurav Prakash Man Upadesh Singh Sachdeva Deepesh Lad Neelam Varma Subhash Varma Pankaj Malhotra 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):183-189.e1
Background
Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting.Patients and Methods
In this retrospective study, 415 consecutive patients with MM managed at a tertiary care center in North India during a study period of January 1, 2010 to December 31, 2015 were evaluated for MPE. The patients with MPE were analyzed for their clinical profile, diagnosis, treatment, and outcomes.Results
Of these 415 patients, 11 (2.65%) patients had MPE. The median age of the study population was 50 years with male preponderance. The majority of these patients had immunoglobin (Ig)G Kappa disease. All patients had higher than International Staging System stage I disease. MPE was a presenting feature at MM diagnosis in 45.45% (n = 5) of the patients, whereas the rest developed MPE during follow-up. MPE presented predominantly (81.8%) as a unilateral effusion. Concurrent extramedullary involvement at other site was seen in 45.45% (n = 5), with 3 (27%) patients having concurrent myelomatous ascites. Six of these were managed aggressively, whereas 5 patients opted for palliation. The outcomes were dismal (90.9% mortality), with a median survival of 2.47 months.Conclusion
MPE is a rare entity, and positive outcomes of therapy remain low with dismal prognosis. 相似文献9.
Walker Mainwaring John Bowers Ngoc Pham Todd Pezzi Mihir Shukla Mark Bonnen Michelle Ludwig 《Clinical breast cancer》2019,19(2):e343-e351
Background
Metastases to the brain occur in 10%-16% of patients with breast cancer, with incidence reportedly increasing. Historically, brain metastases (BM) have been treated with whole-brain radiation therapy (WBRT), but stereotactic radiosurgery (SRS) is an increasingly favored treatment option. In this study we used a population-level database to compare patterns of care and survival between WBRT and SRS for BM from breast cancer.Materials and Methods
The National Cancer Database was used to select patients treated with radiation for BM from primary breast cancer. Groups were classified on the basis of the modality of radiation delivered to the brain and compared across several demographic factors. A Kaplan–Meier survival curve and Cox multivariate analysis were used to compare overall survival. A matched analysis using propensity scores was used to further reduce confounders and compare survival.Results
The treatment groups were significantly different across several socioeconomic variables including income, insurance status, and treatment setting. The percentage of patients who received SRS increased dramatically in the second half of the analyzed time period (P < .001). Unadjusted median survival was significantly longer for patients who received SRS versus those who received WBRT (P < .001). This finding persisted after propensity score-matching.Conclusion
Receipt of SRS was associated with different socioeconomic variables and longer overall survival compared with WBRT, highlighting the need for less toxic treatment for patients who are now living longer. The results revealed important socioeconomic differences between patients selected for SRS versus WBRT and emphasizes disparities in access to modern radiation techniques across the United States. 相似文献10.
Ken Y. Yoneda Judith R. Scranton Michael A. Cadogan Vanessa Tassell Sashi Nadanaciva Keith D. Wilner Nicholas S. Stollenwerk 《Clinical lung cancer》2017,18(5):472-479
Introduction
Interstitial lung disease (ILD) is a rare, but potentially serious, side effect associated with crizotinib, a tyrosine kinase inhibitor for anaplastic lymphoma kinase-positive (ALK+) advanced non–small cell lung cancer. Our objective was to determine the incidence and nature of ILD associated with crizotinib in 4 PROFILE trials (ClinicalTrials.gov identifiers, NCT00585195, NCT00932451, NCT00932893, and NCT01154140).Materials and Methods
Grade ≥ 3 respiratory adverse events (AEs) and serious AEs (SAEs) and any grade AEs/SAEs reported as pneumonitis, ILD, or radiation pneumonitis in trials PROFILE 1001, PROFILE 1005, PROFILE 1007, and PROFILE 1014 were evaluated by an expert independent review committee that included a pulmonologist, medical oncologist, and radiologist. Events were designated as disease progression, de novo ILD possibly or probably related to crizotinib, exacerbation or recurrence of pre-existing ILD, concurrent illness, other toxicity not thought to be related to ILD, or inconclusive.Results
The independent review committee evaluated 446 events (in 368 of 1669 patients who had received crizotinib therapy). They classified these events as follows: progressive disease, 77; de novo ILD, 20; pre-existing ILD, 3; concurrent illness, 9; other toxicities, 310; and inconclusive, 27. The incidence of de novo ILD was 1.2% overall, 1.3% in whites, and 1.2% overall in Asians, but greater at 3.7% in Japanese patients. The median onset of ILD from the initiation of crizotinib therapy was 23 days (range, 3-763 days). The mortality rate due to ILD was 50%. Survival was improved if crizotinib was discontinued on presentation of ILD (9 of 14 patients) compared with discontinued later or continued (1 of 6 patients).Conclusion
ILD associated with crizotinib, although rare, can occur at any time and requires close monitoring. 相似文献11.
Pashtoon Murtaza Kasi Faisal Shahjehan Jordan J. Cochuyt Zhuo Li Dorin Toma Colibaseanu Amit Merchea 《Clinical colorectal cancer》2019,18(1):e87-e95
Background
Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being diagnosed with rectal and colon cancers at our institutions.Patients and Methods
This study included 3381 rectal and colon cancer patients from the Mayo Clinic cancer registry from 1972 to 2017 who were diagnosed with rectal or colon cancer and who were < 50 years old. Patient and cancer characteristics are described. The Cochran-Armitage trend test was used to see if the change in percentage diagnosed at age < 50 years had a significant trend over the years. A linear regression model was fit to estimate the percentage change per year when the trend was approximately linear.Results
The percentage of patients diagnosed with rectal or colon cancer in different age categories over the years showed a rising trend for individuals aged < 50. Most of these tumors were distal (rectum, left-sided colon, and right-sided colon were 49.8%, 28.8%, and 21.4%, respectively). This was more so for patients < 50 diagnosed with rectal cancer, which showed a linear increase at a rate of 0.26% per year (P < .001).Conclusion
Our study affirms the rising proportion of colorectal cancers found in young individuals, with a linear ongoing rise of rectal cancers in particular. This may have implications for the current screening recommendations for colorectal cancers, which are already being revised. 相似文献12.
K.A. Lee M.T.A. Sharabiani D. Tumino J. Wadsley V. Gill G. Gerrard R. Sindhu M.N. Gaze L. Moss K. Newbold 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(6):385-390
Aims
To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series.Materials and methods
Six centres submitted data extracted from historical records on patients aged 18 years or younger, diagnosed between 1964 and 2017. The univariate and multivariable Cox proportional hazard model was used to identify potential predictors of progression-free survival, using national data as a control.Results
Data on 166 patients were available for analysis. Females (74%) were predominant, and the age ranged from 3 to 19 years at diagnosis, mean 14.1 years. Nodal metastases were present in 51%; 12% had distant metastases. After surgery, 95% received radioactive iodine (39% on more than one occasion) and 4% received external beam radiotherapy. With a median follow-up duration of 5 years, 69% are alive with no evidence of disease; 20% are alive with a raised thyroglobulin level as the only evidence of residual disease; 6% have residual structural disease detectable on imaging; 2% have died, from cerebral metastases.Conclusion
Despite most patients having advanced disease at presentation, outcomes are very good. A national prospective registry should allow systematic collection of good-quality data and may facilitate research to further improve outcomes. 相似文献13.
Marianne Grønlie Guren Bjarte Aagnes Mari Nygård Olav Dahl Bjørn Møller 《Clinical colorectal cancer》2019,18(1):e96-e103
Background
Anal squamous cell carcinoma (ASCC) is a rare, human papilloma virus-associated cancer. The purpose was to investigate the population-based incidence rates, age and gender distribution, and survival of ASCC.Materials and Methods
All primary ASCC in 1987 to 2016 were identified in the Cancer Registry of Norway (N = 1548), with information on age, gender, stage, county of residence, radiotherapy, and survival.Results
Median age was 66 years; 71% were females. World age-standardized incidence rates increased (1987-2016) from 0.79 (95% confidence interval [CI], 0.69-0.90) to 1.10 (95% CI, 1.00-1.22) per 100,000 person-years in females and, from 0.34 (95% CI, 0.28-0.42) to 0.47 (95% CI, 0.40-0.54) in males. Estimated annual percentage change was 1.7 (95% CI, 0.9-2.6) for females and 1.3 (95% CI, ?0.1 to 2.7) for males. Incidence rates increased with age; the relative risk was higher in major cities. Five-year net survival increased from 63.4% to 72.7% (1987-2016), but for age ≥ 70 years remained ～57%. Net survival was dependant on stage, age, and gender. Five-year net survival (1997-2016) was 76.4% after curative radiotherapy, and 18.0% after palliative radiotherapy.Conclusion
ASCC incidence rates increased from 1987 to 2016, and survival improved for patients < 70 years. Five-year net survival was 76% after curative radiotherapy in Norway. 相似文献14.
Ayush K. Kapila Allison Herd Natalie Knife Pauly Chaplin Ashraf Patel 《Clinical breast cancer》2019,19(2):e319-e326
Introduction
Breast cancer treatment and recovery remain physically and psychologically challenging for patients. Reflexology has been studied as a complementary therapy to help relieve patients of the physical and psychological stresses involved with breast cancer. As a result of recent positive evidence, we studied its effects quantitatively from 2015 to 2016.Patients and Methods
Fifty-two patients completed pre- and post-reflexology intervention ‘Measure Yourself Concerns and Wellbeing’ (MYCaW) questionnaires. Patients were subdivided into breast cancer (BC) and non-breast cancer (NBC) groups. Concerns raised were subdivided in subcategory groups as per MYCaW guidelines and analyzed for improvements in each domain.Results
Thirty (57.7%) patients in the BC group and 22 (42.3%) patients in the NBC group were analyzed. In the BC group, there was a 46.2% improvement in patients’ concerns, and in the NBC group, a 41.4% improvement in concerns were noted. Overall, the symptoms improved by 44.2% (P < .0001). There was an improvement of 43.4% in patient well-being in the BC group, and a 37.8% change in the NBC group, signifying a total improvement in well-being of 41.2%. There was an improvement of 46.4% in the MYCaW scores; 46.4% in the BC group and 42.6% in the NBC group, signifying a combined average improvement of 42.4%. Patients with poor energy level, sleep problems, stress and tension, and hot flushes and sweats experienced the most improvement in their concerns.Conclusions
Our findings show that reflexology has significantly improved patient-reported outcomes using the MYCaW scale. These findings are encouraging and reflect that increased attention to strategies focusing on improving psychological well-being can help patients in managing their symptoms. 相似文献15.
Filippo Pietrantonio Christian Cotsoglou Giovanni Fucà Salvatore Lo Vullo Federico Nichetti Massimo Milione Jorgelina Coppa Marta Vaiani Alessandra Alessi Michele Prisciandaro Michele Droz-Dit Busset Federica Morano Salvatore Corallo Silvia Lazzati Maria Antista Alessia Mennitto Giovanni Randon Alessandra Raimondi Vincenzo Mazzaferro 《Clinical colorectal cancer》2019,18(1):34-43.e6
Background
In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.Patients and Methods
This was a single-center phase II study enrolling patients with liver-limited, borderline resectable disease and/or high-risk features. Patients received 5 preoperative and 4 postoperative cycles of biweekly COI-B (irinotecan 180 mg/m2 and bevacizumab 5 mg/Kg on day 1, oxaliplatin 85 mg/m2 on day 2, and capecitabine 1000 mg/m2 twice a day on days 2 to 6). The primary endpoint was pathologic response rate in the intention-to-treat population. A Simon 2-stage design was adopted to detect an increase from 30% to 50% with a power of 90%. Dynamic imaging biomarkers (early tumor shrinkage [ETS], deepness of response, maximum standardized uptake volume [SUVmax]/regression index) and next generation sequencing data were explored as surrogates.Results
From June 2013 to March 2017, 46 patients were enrolled. Pathologic response was achieved in 63% patients (endpoint met), and responders achieved significantly better survival outcomes with respect to non-responders. The most frequent grade 3/4 adverse events were diarrhea and neutropenia (8.7%) in the preoperative phase and thromboembolic events (5.9%) in the postoperative phase. ETS and lower SUV-2 were significantly associated with pathologic response.Conclusion
The COI-B regimen is a feasible and highly active perioperative strategy in patients with molecularly unselected, potentially resectable CRCLM. ETS and SUV-2 have a promising role as imaging-based biomarkers for pathologic response. 相似文献16.
James Chih-Hsin Yang Shirish M. Gadgeel Lecia VanDam Sequist Chien-Liang Wu Vassiliki A. Papadimitrakopoulou Wu-Chou Su Joseph Fiore Sanatan Saraf Harry Raftopoulos Amita Patnaik 《Journal of thoracic oncology》2019,14(3):553-559
Introduction
Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with the anti–programmed death 1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 study (NCT02039674).Methods
Adults with previously untreated stage IIIB/IV EGFR-mutant NSCLC were treated with pembrolizumab 2 mg/kg intravenously every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3 + 3 design with cohort expansion. rTumor response was evaluated per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review. The primary objective was determination of a recommended phase 2 dose.Results
Twelve patients enrolled to receive pembrolizumab plus erlotinib and seven to receive pembrolizumab plus gefitinib. No dose-limiting toxicities or grade 5 events occurred. Pembrolizumab plus erlotinib was feasible, with adverse events similar to those expected for monotherapy. However, pembrolizumab plus gefitinib was not feasible due to grade 3/4 liver toxicity in five of seven patients (71.4%), leading to permanent treatment discontinuation in four patients. The most frequently occurring treatment-related adverse events with pembrolizumab plus erlotinib were rash (50.0%), dermatitis acneiform, diarrhea, hypothyroidism, and pruritus (33.3% each). The objective response rate was 41.7%, including response in all four patients with programmed death ligand 1 expression 50% or greater.Conclusions
Although pembrolizumab plus gefitinib was not feasible, the toxicity profile observed with pembrolizumab plus erlotinib suggests combining immunotherapy with anti-EGFR therapy is feasible. Pembrolizumab plus erlotinib did not improve objective response rate compared with previous monotherapy studies; further evaluation would be necessary to evaluate potential effects on other efficacy outcomes. 相似文献17.
Ibiayi Dagogo-Jack Marguerite Rooney Rebecca J. Nagy Jessica J. Lin Emily Chin Lorin A. Ferris Jennifer Ackil Jochen K. Lennerz Richard B. Lanman Justin F. Gainor Alice T. Shaw 《Journal of thoracic oncology》2019,14(5):816-824
Introduction
Circulating tumor DNA analysis is an emerging genotyping strategy that can identify tumor-specific genetic alterations in plasma including mutations and rearrangements. Detection of ROS1 fusions in plasma requires genotyping approaches that cover multiple breakpoints and target a variety of fusion partners. Compared to other molecular subsets of NSCLC, experience with detecting ROS1 genetic alterations in plasma is limited.Methods
To describe the spectrum of ROS1 fusions in NSCLC and determine sensitivity for detecting ROS1 fusions in plasma, we queried the Guardant Health plasma dataset and an institutional tissue database and compared plasma findings to tissue results. In addition, we used the Guardant360 NGS assay to detect potential genetic mediators of resistance in plasma from patients with ROS1-positive NSCLC who were relapsing on crizotinib.Results
We detected seven distinct fusion partners in plasma, most of which (n = 6 of 7) were also represented in the tissue dataset. Fusions pairing CD74 with ROS1 predominated in both cohorts (plasma: n = 35 of 56, 63%; tissue: n = 26 of 52, 50%). There was 100% concordance between the specific tissue- and plasma-detected ROS1 fusion for seven patients genotyped with both methods. Sensitivity for detecting ROS1 fusions in plasma at relapse on ROS1-directed therapy was 50%. Six (33%) of 18 post-crizotinib plasma specimens harbored ROS1 kinase domain mutations, five of which were ROS1 G2032R. Two (11%) post-crizotinib plasma specimens had genetic alterations (n = 1 each BRAF V600E and PIK3CA E545K) potentially associated with ROS1-independent signaling.Conclusions
Plasma genotyping captures the spectrum of ROS1 fusions observed in tissue. Plasma genotyping is a promising approach to detecting mutations that drive resistance to ROS1-directed therapies. 相似文献18.
Michael Mark Dirk Klingbiel Ulrich Mey Ralph Winterhalder Christian Rothermundt Silke Gillessen Roger von Moos Michael Pollak Gabriela Manetsch Räto Strebel Richard Cathomas 《Clinical genitourinary cancer》2019,17(2):e323-e328
Background
There is evidence linking metformin to improved prostate cancer–related outcomes.Patients and Methods
Twenty-five men with metastatic castration-resistant prostate cancer and prostate-specific antigen (PSA) progression while receiving treatment with abiraterone from 3 Swiss centers were included in this single-arm phase 2 trial between November 2013 and September 2016. Metformin was added to abiraterone continuously at 1000 mg twice daily in uninterrupted 4-week cycles. The primary end point was the absence of disease progression at 12 weeks (PFS12). The Fleming single-stage design was applied. With a 5% significance level and 80% power, 25 patients were required to test PFS12 ≤ 15% (H0) compared to ≥ 35% (H1). Secondary end points included toxicity and safety issues. The study was registered at ClinicalTrials.gov (NCT01677897).Results
The primary end point PFS12 was 12% (3 of 25 patients) (95% confidence interval, 3-31). Most patients had PSA progression, almost half had radiographic progression, but only 1 patient had symptomatic progression. Eleven (44%) of 25 patients had grade 1 and 2 patients each grade 2 (8%) or grade 3 (8%) gastrointestinal toxicity (nausea, diarrhea, loss of appetite). One patient discontinued treatment at week 5 because of intolerable grade 3 diarrhea.Conclusion
The addition of metformin to abiraterone for patients with metastatic castration-resistant prostate cancer and PSA progression while receiving abiraterone therapy does not affect further progression and has no meaningful clinical benefit. A higher-than-expected gastrointestinal toxicity attributed to metformin was observed. 相似文献19.
Chien-Hua Tseng Ben-Jei Tsuang Chun-Ju Chiang Kai-Chen Ku Jeng-Sen Tseng Tsung-Ying Yang Kuo-Hsuan Hsu Kun-Chieh Chen Sung-Liang Yu Wen-Chung Lee Tsang-Wu Liu Chang-Chuan Chan Gee-Chen Chang 《Journal of thoracic oncology》2019,14(5):784-792
Introduction
For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM2.5) levels on LC in Taiwan, in relation to contrasting PM2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).Methods
We reviewed 371,084 patients with LC to assess smoking prevalence and correlations between the incidence of adenocarcinoma lung cancer (AdLC) and non-AdLC. Two subsets were selected to assess different AdLC stage trends and the effect of PM2.5 on survival of patients with AdLC.Results
From 1995 to 2015, the proportion of male adult ever-smokers decreased from 59.4% to 29.9% whereas the female smoking rate remained low (3.2% to 5.3%). AdLC incidence in males and females increased from 9.06 to 23.25 and 7.05 to 24.22 per 100,000 population, respectively. Since 1993, atmospheric visibility in NT improved (from 7.6 to 11.5 km), but deteriorated in ST (from 16.3 to 4.2 km). The annual percent change in AdLC stages IB to IV was 0.3% since 2009 (95% confidence interval [CI]: -1.9%–2.6%) in NT, and 4.6% since 2007 (95% CI: 3.3%–5.8%) in ST; 53% patients with LC had never smoked. Five-year survival rates for never-smokers, those with EGFR wild-type genes, and female patients with AdLC were 12.6% in NT and 4.5% in ST (hazard ratio: 0.79, 95% CI: 0.70–0.90).Conclusions
In Taiwan, greater than 50% of patients with LC had never smoked. PM2.5 level changes can affect AdLC incidence and patient survival. 相似文献20.
Yutong Wang Li Bao Bin Chu Shan Gao Minqiu Lu Lei Shi Lina Fu Lijuan Fang Qiuqing Xiang 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):167-176.e1