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1.
Jean-Louis Pujol Laurent Greillier Clarisse Audigier-Valette Denis Moro-Sibilot Lionel Uwer José Hureaux Florian Guisier Delphine Carmier Jeannick Madelaine Josiane Otto Valérie Gounant Patrick Merle Pierre Mourlanette Olivier Molinier Aldo Renault Audrey Rabeau Martine Antoine Marc G. Denis Pierre-Jean Souquet 《Journal of thoracic oncology》2019,14(5):903-913
Introduction
This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum–etoposide chemotherapy.Methods
Patients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O’Brien-Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders.Results
Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval [CI]: 0.0–6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8–33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression-free survival was 1.4 months (95% CI: 1.2–1.5) with atezolizumab and 4.3 months (95% CI: 1.5–5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratioatezolizumab : 0.84, 95% CI: 0.45–1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone).Conclusions
Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed. 相似文献2.
Vinicius Ernani Adams Kusi Appiah Alissa Marr Chi Zhang Weining Zhen Lynette M. Smith Apar Kishor Ganti 《Journal of thoracic oncology》2019,14(3):475-481
Introduction
Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting.Methods
Patients (≥18 years) diagnosed with clinical stages I-II NSCLC from 2004 to 2013 were identified using the National Cancer Database (n = 11,836). The Kaplan-Meier method was used to estimate overall survival (OS) distributions and the log-rank test was used to compare distributions by treatment strategy. Clinical stages I and II were subdivided according to the TNM staging and log-rank tests was used to compare survival distributions by treatment strategy within each subgroup.Results
In patients with T2bN0, median OS in the SBRT alone and SBRT plus adjuvant chemotherapy groups were 16.5 months versus 24.2 months, respectively (95% confidence interval [CI]: 14.1–20.1 months and 18.8–33.3 months, respectively; p < .001); whereas for T3N0, median OS times were 13 months and 20.1 months, respectively (95% CI: 11.7–14.5 mohths and 17.7–21.9 months, respectively; p < .001). For tumors 4 cm or larger and node-negative disease, median OS was 15.9 months in the SBRT-alone group, and 19 months in the SBRT-plus-chemotherapy group (95% CI: 15.1–16.8 months and 17.9–20.8 months, respectively; p < .001). For patients with tumors less than 4 cm and node-negative disease, the median OS was 28.5 months in the SBRT-alone group and 24.3 months in the SBRT-plus-chemotherapy group (95% CI: 27.4–29.4 months and 22.8–26.1 months, respectively; p < .001).Conclusions
SBRT followed by adjuvant chemotherapy was associated with improved OS in comparison with SBRT alone in patients with T greater than or equal to 4 cm, similar to that seen after surgery. 相似文献3.
Rowena Yip Teng Ma Raja M. Flores David Yankelevitz Claudia I. Henschke 《Journal of thoracic oncology》2019,14(5):890-902
Objective
To determine long-term survival of visceral pleural invasion (VPI) and parenchymal invasion (PAI) (angiolymphatic and/or vascular) on survival of NSCLCs less than 30 mm in maximum diameter.Methods
Kaplan-Meier survivals for NSCLCs, with and without VPI and/or PAI, were determined for a prospective cohort of screening participants stratified by pathologic tumor size (≤10 mm, 11–20 mm, and 21–30 mm) and nodule consistency. Log-rank test statistics were calculated.Results
The frequency of PAI versus VPI was significantly lower in patients with subsolid nodules than in those with solid nodules (4.9% versus 27.7% [p < 0.0001]), and correspondingly, Kaplan-Meier lung cancer survival was significantly higher among patients with subsolid nodules (99.1% versus 91.3% [p = 0.0009]). Multivariable Cox regression found that only tumor diameter (adjusted hazard ratio [HR] =1.07, 95% confidence interval [CI]: 1.01–1.14, p = 0.02) and PAI (adjusted HR = 3.15, 95% CI: 1.25–7.90, p = 0.01) remained significant, whereas VPI was not significant (p = 0.15). When clinical and computed tomography findings were included with the pathologic findings, Cox regression showed that the risk of dying of lung cancer increased 10-fold (HR = 10.06, 95% CI: 1.35–75.30) for NSCLCs in patients with solid nodules and more than twofold (by a factor of 2.27) in patients with moderate to severe emphysema (HR = 2.27, 95% CI: 1.01–5.11), as well as with increasing tumor diameter (HR = 1.06, 95% CI: 1.01–1.13), whereas PAI was no longer significant (p = 0.19).Conclusions
Nodule consistency on computed tomography was a more significant prognostic indicator than either PAI or VPI. We propose that patients with NSCLC with VPI and a maximum tumor diameter of 30 mm or less not be upstaged to T2 without further large, multicenter studies of NSCLCs, stratified by the new T status and that classification be considered separately for patients with subsolid or solid nodules. 相似文献4.
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5.
Jessica J. Lin Ginger Y. Jiang Nencyben Joshipura Jennifer Ackil Subba R. Digumarthy Sandra P. Rincon Beow Y. Yeap Justin F. Gainor Alice T. Shaw 《Journal of thoracic oncology》2019,14(4):683-690
Background
Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases.Methods
In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as ≥1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1.Results
Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval [CI]: 44.9%–92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%–100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months–not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%–90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%–100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months–not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy.Conclusions
Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases. 相似文献6.
V. Jenkins I. Solis-Trapala H. Payne M. Mason L. Fallowfield S. May L. Matthews S. Catt 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):99-107
Aims
Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment.Material and methods
Men with mCRPC from 20 UK cancer centres starting various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months.Results
In total, 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate [FACT-P] mean = –3.89, 95% confidence interval –6.7 to –1.05, P = 0.007; Trial Outcome Index [TOI] analysis mean = –3.10, 95% confidence interval –5.34 to –0.83, P = 0.007). Those who came off novel therapy and remained on luteinising hormone-releasing hormone agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale mean difference = –4.45, 95% confidence interval –7.06 to –1.83, P = 0.001; TOI mean difference = –5.62, 95% confidence interval –10.97 to –0.26, P = 0.040). At 3 and 6 months, men who reported pain at baseline improved (43%, 40%), but for others pain levels remained the same (45%, 42%) or worsened (13%, 18%). Information regarding supportive care was lacking throughout the period of time on the study.Conclusion
Most mCRPC treated patients experience reduced QoL and inadequate pain control. More help with pain management and better information provision regarding supportive care is warranted. 相似文献7.
Omar Abdel-Rahman Yuan Xu Shiying Kong Joseph Dort May Lynn Quan Safiya Karim Antoine Bouchard-Fortier HyoKeun Cho Winson Y. Cheung 《Clinical breast cancer》2019,19(2):e297-e305
Introduction
The aim of this study was to characterize treatment trends and outcomes of women who have preexisting cardiovascular disease (CVD) prior to the diagnosis of breast cancer.Patients and Methods
This represented a retrospective, population-based cohort study that analyzed pooled data from the provincial cancer registry, physician billing claims, hospital discharge abstracts, ambulatory care, and the 2011 census in a large Canadian province. Multivariable logistic regression was performed to identify the associations of CVD with breast cancer treatment and outcomes. Kaplan-Meier analyses were conducted and survival was compared between CVD and non-CVD groups. Cox regression models were constructed to determine the effect of CVD on overall and cancer-specific survival.Results
A total of 25,594 women with breast cancer were eligible and included in the current analysis. Preexisting CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.48-0.66; P < .0001) and radiotherapy (OR, 0.75; 95% CI, 0.67-0.83; P < .0001), but a higher probability of undergoing mastectomy (OR, 1.13; 95% CI, 1.03-1.25; P = .011). Unadjusted Kaplan-Meier analyses showed that individuals with preexisting CVD experienced worse median overall and cancer-specific survival when compared with those without CVD (87 vs. 150 months and 106 vs. 131 months, respectively; both P < .0001). Adjusting for measured confounders, the presence of preexisting CVD continued to predict for worse overall survival (hazard ratio, 1.55; 95% CI, 1.43-1.67; P < .0001), but not cancer-specific survival (hazard ratio, 1.11; 95% CI, 0.98-1.27; P = .099).Conclusions
Patients with breast cancer with preexisting CVD are less likely to receive recommended treatment for their cancer and more likely to exhibit worse overall survival. 相似文献8.
Chih-An Lin Sung-Liang Yu Hsuan-Yu Chen Huei-Wen Chen Shr-Uen Lin Chia-Ching Chang Chong-Jen Yu Pan-Chyr Yang Chao-Chi Ho 《Journal of thoracic oncology》2019,14(3):513-526
Introduction
Approximately 5% of patients with EGFR-activating mutations acquire EGFR tyrosine kinase inhibitor (TKI) resistance through SCLC transformation. However, the reason for the poor outcome and the molecular basis of EGFR-mutant SCLC that has transformed from adenocarcinoma remain unclear.Methods
In this study, we established two EGFR-mutant SCLC cell lines from lung adenocarcinoma patients after failed EGFR-TKI treatment to investigate their molecular basis and potential therapeutic strategies in the hope of improving patient outcome.Results
These two EGFR-mutant SCLC cell lines displayed two different phenotypes: suspensive and adherent. Both phenotypes shared the same genomic alterations analyzed by array-based comparative genomic hybridization assay. Increased expression of EGFR and mesenchymal markers and decreased expression of neuroendocrine markers were observed in adherent cells. Principal component analysis and hierarchical clustering analysis of RNA microarray revealed that these two cell lines displayed a unique gene expression pattern that was distinctly different from that in NSCLC and classical SCLC cells. Combined treatment using an EGFR-TKI and an AKT inhibitor attenuated cell viabilities in our two cell lines. Moreover, the use of a histone deacetylase inhibitor significantly inhibited the cell viabilities of both cell lines in vitro and in vivo.Conclusion
Our findings suggest that EGFR-mutant SCLC may be a distinct subclass of SCLC that exhibits epithelial-mesenchymal transition phenotypes, and adding an AKT or histone deacetylase inhibitor to pre-existing therapies may be one of the therapeutic choices for transformed EGFR-mutant SCLC. 相似文献9.
Khurum Khan Jayant K. Rane David Cunningham Sheela Rao David Watkins Naureen Starling Eleftheria Kalaitzaki Martin Forster Chiara Braconi Nicola Valeri Marco Gerlinger Ian Chau 《Clinical colorectal cancer》2019,18(1):64-71.e1
Background
Gastrointestinal (GI) cancer patients may not be considered for therapy with fluoropyrimidines (FPs) because of previous cardiovascular (CV) toxicity or preexisting risk factors; such patients may benefit from raltitrexed-based therapy.Patients and Methods
Patient, tumor, and treatment characteristics, as well as clinical outcomes of all consecutively treated patients with raltitrexed at the Royal Marsden Hospital between October 1998 and July 2011 were examined. GI cancer patients who developed CV toxicity as a result of FPs and those with significant CV risk factors receiving raltitrexed were included in this analysis.Results
A total of 247 patients (155 and 92 with CV FP-related CV toxicities and significant CV risk factors, respectively) treated with raltitrexed alone or in combination were examined after a median follow-up of 47.1 months. CV toxicity profiles of patients receiving capecitabine (n = 110) and 5-fluorouracil (n = 45) were largely similar. Of raltitrexed-treated patients, 13 (5%) experienced CV toxicities and 1 (< 0.1%) died as a result of myocardial infarction. The median progression-free survival (PFS) and overall survival (OS) were 36.0 months (95% confidence interval [CI], 26.5-48.6) and 44.3 months (95% CI, 33.1-56.8), respectively. The 5-year survival for early stage GI malignancies (n = 140) was 62.0% (95% CI, 50.1-71.9). Median PFS and OS were not reached in this group (interquartile range = 38.4 months to NR); median PFS and OS for advanced GI malignancies (n = 107) were 18.8 (95% CI, 11.9-25.7) and 23.7 months (95% CI, 17.0-26.9), respectively.Conclusion
A raltitrexed-based regimen is well-tolerated therapy with comparable efficacy to FPs in patients with GI malignancies with significant CV toxicities or risk factors. 相似文献10.
Ryuma Tokunaga Shu Cao Madiha Naseem Jae Ho Lo Francesca Battaglin Alberto Puccini Martin D. Berger Shivani Soni Joshua Millstein Wu Zhang Sebastian Stintzing Fotios Loupakis Chiara Cremolini Volker Heinemann Alfredo Falcone Heinz-Josef Lenz 《Clinical colorectal cancer》2019,18(1):e8-e19
Background
Adenosine has an immunosuppressive and angiogenic modulation of the tumor microenvironment. The present study explored the efficacy of single nucleotide polymorphisms (SNPs) in adenosine-related molecules for patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy.Patients and Methods
We analyzed genomic DNA extracted from 451 samples from 3 independent cohorts: a discovery cohort of 107 patients treated with FOLFIRI (5-fluorouracil, leucovorin, oxaliplatin, irinotecan) plus bevacizumab in FIRE-3 (ClinicalTrials.gov identifier, NCT00433927); a validation cohort of 215 patients with FOLFIRI plus bevacizumab in TRIBE (ClinicalTrials.gov identifier, NCT00719797); and a control cohort of 129 patients treated with FOLFIRI plus cetuximab in FIRE-3. The relationship between the selected SNPs and clinical outcomes was analyzed.Results
In the discovery cohort, patients with any C allele in CD39 rs11188513 had significantly shorter median progression-free survival compared with those with the T/T variant (11.3 vs. 13.1 months; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .022) on univariate analysis. Also, their overall survival (OS) was shorter (27.4 vs. 49.9 months; HR, 2.10; 95% CI, 1.07-4.10; P = .031) on univariate and multivariable analyses. The significant association between CD39 rs11188513 and OS was confirmed in the validation cohort (25.8 vs. 31.6 months; HR, 1.53; 95% CI, 1.09-2.15; P = .013). CD73 rs2229523 and A2BR rs2015353 in the discovery cohort and CD39 rs2226163 in the validation cohort showed significant correlations with OS on univariate and multivariable analyses. None of SNPs were significant in the cetuximab control cohort.Conclusion
Selected SNPs in the adenosine pathway could affect the clinical outcomes of patients with metastatic colorectal cancer treated with FOLFIRI plus bevacizumab. 相似文献11.
Xiaoliang Zhao Bhaskar Kallakury Joeffrey J. Chahine Dan Hartmann YuWen Zhang Yulong Chen Hua Zhang Bin Zhang Changli Wang Giuseppe Giaccone 《Journal of thoracic oncology》2019,14(5):914-923
Introduction
Surgery in SCLC is limited to very early stages, but several reports suggest a potential broader role. Little is known of the influence of microenvironment on the biology of SCLC.Methods
We assessed the clinical prognostic factors in a large series of resected SCLC patients. The prognostic value of programmed cell death ligand 1 (PD-L1) expression in tumor cells and tumor infiltrating lymphocytes (TILs) and the percentage of CD3-, CD20-, CD45- and CD68-positive cells, were also investigated.Results
Two hundred five SCLC cases were resected between 2005 and 2015 and the median follow-up was 29 months (range: 2 to 135 months). Median survival of all patients was 69 months, and 5-year survival rates were 63.8%, 65.5%, 34.9%, and 0% for pathologic stages I, II, III, and IV, respectively. By multivariate analysis complete resection, cigarette index, lymph node metastatic rate, percentage of CD3-positive cells, PD-L1 expression in tumor cells, and TILs were independent prognostic factors. High PD-L1 expression was present in 3.2% and 33.5% of all tumor samples in tumor cells and TILs, respectively. High PD-L1 expression in tumor cells or TILs correlated with shorter survival, whereas high expression of CD3, CD20, and CD45 correlated with better survival.Conclusions
Resected stage II SCLC patients have similar survival as stage I, suggesting that surgery could be extended to patients with hilar lymph node involvement. Survival was better in tumors with a higher percentage of T cells and B cells, whereas PD-L1 expression in tumor cells and TILs correlated with worse survival, which suggests a potential role of immunotherapy in resected SCLC. 相似文献12.
Chen Suo Yajun Yang Ziyu Yuan Tiejun Zhang Xiaorong Yang Tao Qing Pei Gao Leming Shi Min Fan Hongwei Cheng Ming Lu Li Jin Xingdong Chen Weimin Ye 《Journal of thoracic oncology》2019,14(4):712-725
Introduction
Studies have reported alcohol consumption and genetic variants as major contributing factors for esophageal squamous cell carcinoma (ESCC). However, the complicated interactions between alcohol and genetic factors involved in alcohol metabolism have not been well elucidated with respect to augmented risk of ESCC.Methods
We performed a large population-based case-control study in a Chinese city with a high ESCC incidence by enrolling 1190 case patients and 1883 controls. We integrated candidate single-nucleotide polymorphism data, detailed alcohol consumption records, gene-alcohol interactions, and single-nucleotide polymorphism functional information to untangle the complicated relationship between alcohol, variants of genes encoding alcohol metabolism enzymes, and ESCC risk. The gene-alcohol interaction was tested by including their product term in a multivariable logistic regression model. Synergy index and ratio of ORs were calculated to assess interaction on additive and multiplicative scale, respectively.Results
We confirmed two ESCC susceptibility loci, rs671 in aldehyde dehydrogenase 2 family member gene (ALDH2) and rs1042026 in alcohol dehydrogenase 1B (class I), beta polypeptide gene (ADH1B), that significantly altered alcohol consumption behavior and subsequently modified the association between alcohol consumption and ESCC risk. The rs671(A) allele was associated with ESCC risk in alcohol drinkers (adjusted odds ratio =1.98, 95% confidence interval [CI]: 1.51–2.60) but not in nondrinkers. Healthy individuals who carry different ALDH2 and ADH1B genotypes exhibit diversified drinking behavior, with the proportion of drinkers varying between 23.7% and 54.3%. Among individuals with a fast ethanol oxidization rate, we observed a strong interaction between heavy alcohol consumption and ethanal oxidization rate on both the additive scale (synergy index 4.80 [95% CI: 1.82–12.68]) and the multiplicative scale (ratio of ORs 2.93, 95% CI: 1.39–6.35).Conclusions
Our observation highlights the need for preventing excessive use of alcohol, especially in individuals harboring active alcohol dehyrogenase and inactive ALDH2 variants. 相似文献13.
Grace G. Wong Vincent Ha Michael P. Chu Deonne Dersch-Mills Sunita Ghosh Carole R. Chambers Michael B. Sawyer 《Clinical colorectal cancer》2019,18(1):72-79
Background
First-line adjuvant chemotherapy options for early-stage colorectal cancer (CRC) include CapeOx (capecitabine, intravenous oxaliplatin) and FOLFOX (intravenous 5-fluorouracil, leucovorin, oxaliplatin). Capecitabine is an oral prodrug analog of 5-fluorouracil, and recent studies have suggested that proton pump inhibitors (PPIs) may detrimentally affect capecitabine efficacy. Conversely, some literature suggests that PPIs may negatively affect CRC itself. To gain insight into the nature of PPIs’ effect on capecitabine and CRC, we investigated their effects on effectiveness of CapeOx versus FOLFOX chemotherapy.Patients and Methods
We conducted a retrospective chart review of 389 patients with stage II-III CRC who received adjuvant CapeOx or FOLFOX from 2004 to 2013. Information regarding PPI receipt, chemotherapy, and patient outcomes from medical records was analyzed.Results
Three-year recurrence-free survival was significantly lower in CapeOx-treated PPI recipients than non-PPI recipients (69.5 vs. 82.6%; P = .029). Unadjusted analysis showed that CapeOx-treated PPI recipients were twice as likely to experience cancer recurrence or death as CapeOx-treated non-PPI recipients (hazard ratio = 2.03; 95% confidence interval, 1.06-3.88; P = .033). FOLFOX-treated PPI recipients had a non–statistically significant difference in 3-year recurrence-free survival versus non-PPI recipients (82.9 vs. 61.7%; P = .066) and a non–statistically significant difference in recurrence/death (hazard ratio = 0.51; 95% confidence interval, 0.25-1.06; P = .071). No significant differences were seen in overall survival between groups.Conclusion
Our results suggest PPIs negatively affected recurrence-free survival in CapeOx-treated CRC patients and yielded no significant effects among FOLFOX-treated patients, potentially implicating a pharmacokinetic interaction between PPIs and capecitabine. No overall survival effects were seen. Given PPIs’ widespread use, further studies are required to corroborate our findings. 相似文献14.
C.M. Jones K. Spencer C. Hitchen T. Pelly B. Wood P. Hatfield A. Crellin D. Sebag-Montefiore R. Goody T. Crosby G. Radhakrishna 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(6):356-364
Aims
Chemoradiotherapy (CRT) is established as a superior treatment option to definitive radiotherapy in the non-surgical management of oesophageal cancer. For patients precluded from CRT through choice or comorbidity there is little evidence to guide delivery of single-modality radiotherapy. In this study we outline outcomes for patients unfit for CRT who received a hypofractionated radiotherapy (HRT) regimen.Materials and methods
A retrospective UK single-centre analysis of 61 consecutive patients with lower- or middle-third adenocarcinoma (OAC; 61%) or squamous cell carcinoma of the oesophagus managed using HRT with radical intent between April 2009 and 2014. Treatment consisted of 50 Gy in 16 fractions (n = 49, 80.3%) or 50–52.5 Gy in 20 fractions (n = 12, 19.7%). Outcomes were referenced against a contemporaneous comparator cohort of 80 (54% OAC) consecutive patients managed with conventionally fractionated CRT within the same centre.Results
Three-year and median overall survival were, respectively, 56.9% and 29 months with HRT compared with 55.5% and 26 months for CRT; adjusted hazard ratio 0.79 (95% confidence interval 0.48–1.28). Grade 3 and 4 toxicity rates were low at 16.4% (n = 10) for those receiving HRT and 40.2% (n = 32) for the CRT group. In patients with OAC, CRT delivered superior overall survival (hazard ratio 0.46; 95% confidence interval 0.25–0.85) and progression-free survival (hazard ratio 0.45; 95% confidence interval 0.23–0.88) when compared with HRT.Conclusions
The HRT regimen described here was safe and tolerable in patients unable to receive CRT, and delivered promising survival outcomes. The use of HRT for the treatment of oesophageal cancer, both alone and as a sequential or concurrent treatment with chemotherapy, requires further study. New precision radiotherapy technologies may provide additional scope for improving outcomes in oesophageal cancer using HRT-based approaches and should be evaluated. 相似文献15.
Yaqi Li Yang Feng Weixing Dai Qingguo Li Sanjun Cai Junjie Peng 《Clinical colorectal cancer》2019,18(1):e104-e116
Background
The prognostic value of tumor sidedness in metastatic colorectal cancer (CRC) has been established, but its impact on nonmetastatic disease remains unclear. Our study aimed to explore the prognostic effect of tumor sidedness by subgroup survival analyses, according to histology and tumor grade in stage I-IV CRCs.Methods
A retrospective population-based study was conducted based on Surveillance, Epidemiology and End Results (SEER) data. Population data in the SEER 9 registry (1975-2014) were used to determine survival trends of CRCs, and associated population data in the SEER 18 registry (2000 to 2014) were used to assess the prognostic impact of tumor sidedness on CRCs.Results
The 5-year cause-specific survival for all subgroups of CRCs improved from 1975 to 2014. Of 238,826 patients, 44.2% had right-sided cancer. Patients with right-sided cancer were more likely to be older, to be women, to have disease of mucinous or signet-ring cell histology, to have more poorly differentiated tumors, and to be diagnosed with a more advanced disease stage. Multivariate Cox regression showed stage I-II right-sided cancers had better cause-specific survival than the left-sided cancers (left colon: hazard ratio [HR] = 1.091, 95% confidence interval [CI], 1.052-1.132; rectum: HR = 1.363; 95% CI, 1.304-1.425; P < .001), while stage III and IV right-sided cancers had worse cause-specific survival. In subgroup analyses by histology and tumor grade within stage III CRCs, right-sided poorly differentiated mucinous adenocarcinoma showed significantly better survival (left colon: HR = 1.352; 95% CI, 1.145-1.596; rectum: HR = 1.125; 95% CI, 0.916-1.381; P = .002).Conclusion
The relationship between sidedness and prognosis in CRCs depends on stage and histopathologic characteristics, especially for stage III disease. 相似文献16.
M. Iachina P.M. Ljungdalh R.G. Sørensen L. Kaerlev J. Blaakær O. Trosko N. Qvist B.M. Nørgård 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):115-123
Aims
To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.Materials and methods
The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.Results
In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).Conclusions
We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis. 相似文献17.
Yamila Goenaga Vázquez Fernando Cabanillas Joel Rivera Concepción Olga L. Díaz Miranda 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):e153-e158
Background
Although most cases of herpes zoster (HZ) are self-limited, lymphoma patients are at greater risk for recurrences and more serious and atypical complications that can delay scheduled anti-lymphoma treatment or prevent its continuation.Patients and Methods
This is a cohort study with a retrospective chart review of 415 patients diagnosed with lymphoma to determine the incidence and risk factors for developing HZ among this population. Data collected included date of diagnosis, patient’s age, last follow-up or death, stage and presentation of lymphoma, treatment type, baseline laboratory tests, and comorbidities. Patients with a diagnosis of HZ at any time during their course of illness were identified. Patients were divided into various subgroups to analyze their risk of developing HZ individually. The frequencies of each categorical variable were compared with χ2 tests. Relative risks were calculated using 95% confidence intervals (CIs).Results
During a median follow-up of 8.9 years, 46 cases of HZ were identified, with an overall incidence density of 11.1%. Higher rates of HZ were associated with lymphocytopenia (P = .038), presentation (P = .030), stage (P = .034), autologous stem cell transplant (P = .019), multiple courses of chemotherapy (P = .035), and fludarabine therapy (P = .002). Those who received what we labeled as ‘highly immunosuppressive chemotherapy’ had 2.9 times the risk to develop HZ than those who did not receive this therapy (95% CI, 1.47-5.623; P < .001).Conclusions
Receiving highly immunosuppressive chemotherapy is an independent risk factor for developing HZ. Patients with the risk factors described here might benefit from antiviral prophylaxis against HZ. 相似文献18.
Ting Ye Lin Deng Shengping Wang Jiaqing Xiang Yawei Zhang Hong Hu Yihua Sun Yuan Li Lei Shen Li Xie Wenchao Gu Yue Zhao Fangqiu Fu Weijun Peng Haiquan Chen 《Journal of thoracic oncology》2019,14(4):617-627
Introduction
The clinicopathologic features and prognostic predictors of radiological part-solid lung adenocarcinomas were unclear.Methods
We retrospectively compared the clinicopathologic features and survival times of part-solid tumors with those of pure ground glass nodules (pGGNs) and pure solid tumors treated with surgery at Fudan University Shanghai Cancer Center and evaluated the prognostic implications of consolidation-to-tumor ratio (CTR), solid component size, and tumor size for part-solid lung adenocarcinomas.Results
A total of 911 patients and 988 pulmonary nodules (including 329 part-solid nodules [PSNs], 501 pGGNs, and 158 pure solid nodules) were analyzed. More female patients (p = 0.015) and nonsmokers (p = 0.003) were seen with PSNs than with pure solid nodules. The prevalence of lymphatic metastasis was lower in patients with PSNs than in those with pure solid tumors (2.2% versus 27% [p < 0.001]). The 5-year lung cancer–specific (LCS) recurrence-free survival and LCS overall survival of patients with PSNs were worse than those of patients with pGGNs (p < 0.001 and p = .042, respectively) but better than those of patients with pure solid tumors ([p < 0.001 and p < 0.0001, respectively]). CTR (OR = 12.90; 95% confidence interval [CI]: 1.85–90.04), solid component size (OR = 1.45; 95% CI: 1.28–1.64), and tumor size (OR = 1.23; 95% CI: 1.15–1.31) could predict pathologic invasive adenocarcinoma for patients with PSNs. None of them could predict the prognosis. Patients receiving sublobar resection had prognoses comparable to those of patients receiving lobectomy (p = .178 for 5-year LCS recurrence-free survival and p = .319 for 5-year LCS overall survival). The prognostic differences between patients with systemic lymph node dissection and those without systemic lymph node dissection were statistically insignificant.Conclusions
Part-solid lung adenocarcinoma showed clinicopathologic features different from those of pure solid tumor. CTR, solid component size, and tumor size could not predict the prognosis. Part-solid lung adenocarcinomas define one special clinical subtype. 相似文献19.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献20.
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