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1.
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2.
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3.
Suzanne B. Merrill Brian S. Sohl Ashiya Hamirani Erik B. Lehman Kathleen K. Lehman Matthew G. Kaag Jay D. Raman 《Clinical genitourinary cancer》2019,17(2):132-138
Introduction
The purpose of this study was to explore whether the practice of postoperative renal cell carcinoma (RCC) surveillance affords a survival benefit by investigating whether detection of RCC recurrences in an asymptomatic versus symptomatic manner influences mortality.Patients and Methods
We identified 737 patients who underwent partial or radical nephrectomy for M0 RCC between 1998 and 2016. Overall survival and disease-specific survival stratified by the type of recurrence detection (asymptomatic vs. symptomatic) was estimated using Kaplan-Meier probabilities both from the time of surgery and from the time of recurrence. Cox proportional hazard regression models were used to evaluate the impact of the type of recurrence detection on mortality.Results
A total of 78 patients (10.6%) experienced recurrence after surgery, of whom 63 (80.8%) were asymptomatic (detected using routine surveillance) and 15 (19.2%) were symptomatic. The median postoperative follow-up was 47.2 months (interquartile range, 26.3-89.4 months). Five- and 10-year overall survival, from time of surgery, among patients with asymptomatic versus symptomatic recurrences was 57% and 39% versus 24% and 8%, respectively (P = .0002). As compared with asymptomatic recurrences, patients with symptomatic recurrences had an increased risk of overall (OD) and disease-specific death (DSD) both when examined from the time of surgery (OD: hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.33-7.49; P = .0091 and DSD: HR, 3.44; 95% CI, 1.38-8.57; P = .0079) and from the time of recurrence (OD: HR, 2.93; 95% CI, 1.24-6.93; P = .0143 and DSD: HR, 3.62; 95% CI, 1.45-9.01; P = .0058).Conclusions
Capturing RCC recurrences in an asymptomatic manner during routine surveillance is associated with improved patient survival. 相似文献4.
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5.
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6.
Martin Reck Leora Horn Silvia Novello Fabrice Barlesi István Albert Erzsébet Juhász Dariusz Kowalski Gilles Robinet Jacques Cadranel Paolo Bidoli John Chung Arno Fritsch Uta Drews Andrea Wagner Ramaswamy Govindan 《Journal of thoracic oncology》2019,14(4):701-711
Introduction
This phase II study evaluated the efficacy and safety of the pan-cyclin–dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.Methods
In this randomized, double-blind study, unselected patients with previously untreated extensive-disease SCLC received roniciclib, 5 mg, or placebo twice daily according to a 3 days–on, 4 days–off schedule in 21-day cycles, with concomitant cisplatin or carboplatin on day 1 and etoposide on days 1 to 3. The primary end point was progression-free survival. Other end points included overall survival, objective response rate, and safety.Results
A total of 140 patients received treatment: 70 with roniciclib plus chemotherapy and 70 with placebo plus chemotherapy. Median progression-free survival times was 4.9 months (95% confidence interval [CI]: 4.2–5.5) with roniciclib plus chemotherapy and 5.5 months (95% CI: 4.6–5.6) with placebo plus chemotherapy (hazard ratio [HR] = 1.242, 95% CI: 0.820–1.881, p = 0.8653). Median overall survival times was 9.7 months (95% CI: 7.9–11.1) with roniciclib plus chemotherapy and 10.3 months (95% CI: 8.7–11.9) with placebo plus chemotherapy (HR = 1.281, 95% CI: 0.776–1.912, p = 0.7858). The objective response rates were 60.6% with roniciclib plus chemotherapy and 74.6% with placebo plus chemotherapy. Common treatment-emergent adverse events in both groups included nausea, vomiting, and fatigue. Serious treatment-emergent adverse events were more common with roniciclib plus chemotherapy (57.1%) than with placebo plus chemotherapy (38.6%).Conclusions
Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with extensive-disease SCLC, and the study was prematurely terminated. 相似文献7.
Alp Tuna Beksac Mesude Bicak Ishan Paranjpe David J. Paulucci John P. Sfakianos Ketan K. Badani 《Clinical genitourinary cancer》2019,17(2):e314-e322
Background
Chromophobe renal cell carcinoma (chRCC) is known as an indolent tumor; however, mortality still occurs. We sought to determine the clinicopathologic and genomic factors associated with aggressive chRCC.Patients and Methods
Two different datasets were used to identify patients with clinical stage III and IV chRCC. Eighteen patients from The Cancer Genome Atlas (TCGA) database and 1693 patients from the American College of Surgeons National Cancer Database (NCDB) were used for analysis. From the TCGA, RNA-Seq expression analysis of 18,745 genes was conducted between the recurrent (n = 5; 27.8%) and nonrecurrent patients (n = 13; 72.2%). Biological significance was identified via pathway enrichment and gene function analyses. From the NCDB, Cox proportion hazards regression models were used to identify variables associated with overall survival (OS) at a median follow-up of 41.4 months.Results
Between the 2 groups, 2182 genes were differentially expressed. The most commonly overexpressed pathways were neuroactive ligand-receptor interactions and cytokine-cytokine receptor interactions. The most activated gene functions were cellular, metabolic, and multicellular organismal processes. In the NCDB, multivariable analysis, age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03-1.05; P < .001), TNM stage IV versus III (HR, 3.86; 95% CI, 2.98-5.00; P < .001), and positive surgical margin (HR, 1.68; 95% CI, 1.45-1.96; P < .001) were associated with worse OS at a median follow-up of 41.4 months. Five-year OS was significantly lower for stage IV patients compared with stage III patients (80.0% vs. 29.9%; P < .001).Conclusions
Patients with recurrent chRCC demonstrated a differential gene expression of specific biochemical pathways. Clinical parameters associated with worse OS included age, stage, and positive surgical margin. 相似文献8.
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9.
Omar Abdel-Rahman 《Clinical genitourinary cancer》2019,17(2):e329-e338
Background
The objective of the study was to evaluate the outcomes of clinically localized prostate cancer treated with prostatectomy versus radiation therapy within the context of a prospective prostate cancer screening study.Patients and Methods
Within the PLCO (Prostate, Lung, Colorectal, and Ovary) trial, patients who were diagnosed with clinically localized prostate cancer and subsequently received treatment with prostatectomy or radiation therapy (with or without hormonal treatment) were included. Univariate and multivariate Cox regression analyses were then performed to determine factors affecting overall and prostate cancer-specific survival. Factors with P < .05 in univariate analysis were included in the multivariate analysis.Results
A total of 3953 patients were included in the current analysis. These included 2044 patients treated with prostatectomy and 1909 patients treated with radiation therapy with or without hormonal treatment. In an adjusted multivariate analysis for factors affecting overall survival, prostatectomy was associated with better overall survival compared with radiation therapy (hazard ratio, 0.548; 95% confidence interval [CI], 0.440- 681; P < .001). Likewise, in an adjusted multivariate analysis for factors affecting prostate cancer-specific survival, prostatectomy was associated with better prostate cancer-specific survival compared with radiation therapy (hazard ratio, 0.485; 95% CI, 0.286- 0.822; P = .007). Similar findings were found with propensity score matching and repeating the same analyses on the post-matching cohort.Conclusion
Prostatectomy seems to predict better overall and prostate cancer-specific survival compared with radiation therapy among patients with clinically localized prostate cancer diagnosed within the PLCO trial. 相似文献10.
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11.
Zabi Wardak Alana Christie Alex Bowman Strahinja Stojadinovic Lucien Nedzi Sam Barnett Toral Patel Bruce Mickey Tony Whitworth Raquibul Hannan James Brugarolas Robert Timmerman 《Clinical genitourinary cancer》2019,17(2):e273-e280
Background
Brain metastases (BM) pose a significant problem in patients with metastatic renal-cell carcinoma (mRCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.Patients and Methods
The mRCC patients with BM treated with SRS were reviewed. Patient demographics, clinical history, and SRS treatment parameters were identified.Results
Among 268 patients with mRCC treated between 2006 and 2015, 38 patients were identified with BM. A total of 243 BM were treated with SRS with 1 to 26 BMs treated per SRS session (median, 2 BMs). The median (range) BM size was 0.6 (0.2-3.1) cm and median (range) SRS treatment dose was 18 (12-24) Gy. Treated BM local control rates at 1 and 2 years were 91.8% (95% confidence interval, 85.7-95.4) and 86.1% (95% confidence interval, 77.1-91.7), respectively. BM control declined for larger tumors. Survival after 1-year was 57.5% (95% CI 40.2-71.4) for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM. Survival was prognostic based on International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups in patients with < 5 BM. Two patients experienced grade 3 radiation necrosis requiring surgical intervention.Conclusion
SRS is effective in controlling BM in patients with mRCC. Over half of treated patients survive past a year, and no differences in survival were noted in patients with > 5 metastases. Prognostic risk categories based on systemic disease (IMDC) are predictive of survival in this BM population, with limited rates of symptomatic radiation necrosis. 相似文献12.
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13.
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14.
I. Mallick A. Das M. Arunsingh 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(4):260-264
Aims
Node-positive prostate cancer is a unique subgroup, with varied practice on locoregional treatment. Definitive treatment with hypofractionated radiotherapy has not been widely reported. We have routinely used standard regimens of hypofractionated radiotherapy for node-positive disease and report our results of toxicity, biochemical control and survival.Materials and methods
Medical records of patients diagnosed with prostate cancer between February 2011 and April 2016 with radiologically involved pelvic nodes on magnetic resonance imaging/computed tomography without distant metastases were analysed. All patients were treated with long-term androgen deprivation therapy (ADT) and hypofractionated radiotherapy. Acute and late toxicities were assessed using Radiation Therapy Oncology Group acute and late morbidity scoring criteria. Biochemical control and survival were computed using Kaplan–Meier survival statistics.Results
In total, 61 patients were identified with node-positive disease, with a median age of 68 years and a median initial prostate-specific antigen level of 40.1 ng/ml. Most, 50 (81.9%), had T3 disease; 47.6% had Gleason 8–10 disease. All were treated with hypofractionated intensity-modulated radiotherapy, predominantly 60 Gy/20 fractions/4 weeks, with a dose of 44 Gy/20 fractions to the pelvic nodes. Twenty-five patients (41%) who had residual radiologically enlarged nodes after 3–6 months of ADT received nodal boost to the involved nodes, to a dose of 54–60 Gy as simultaneous boost. Incidences of late grade 2 + gastrointestinal and genitourinary toxicities were 13.1 and 18%, respectively, with no grade 4 toxicities. With a median follow-up of 48 months, 15 (24.6%) patients developed biochemical failure, with only four locoregional failures. The 4-year biochemical control rate was 77.5% and overall survival was 91%. Patients who had residual enlarged nodes after initial ADT had worse biochemical control (53.9% versus 93.1% at 4 years, P < 0.001).Conclusion
Moderately hypofractionated radiotherapy using an established fractionation schedule with long-term ADT for node-positive prostate cancer patients is feasible and results in excellent biochemical control rates at 4 years, with acceptable late toxicity rates. The response to initial ADT predicts outcomes. 相似文献15.
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16.
T. Steinmeier S. Schulze Schleithoff B. Timmermann 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(3):142-150
Aims
Childhood cancer is rare and survival of childhood cancer has increased up to 80% at 5 years after diagnosis. Radiotherapy is an important element of the multimodal treatment concept. However, due to growing tissue, children are particularly sensitive to radiation-related side-effects and the induction of secondary malignancies. However, radiotherapy techniques have continuously progressed. In addition, modern treatment concepts have been improved in order to minimise long-term effects. Today, radiotherapy is used for various tumour types in childhood, such as sarcomas and tumours of the central nervous system.Materials and methods
External beam therapy with either photons or protons and brachytherapy are predominantly used for the treatment of childhood tumours. Technical developments and features, as well as clinical outcomes, for several tumour entities are presented.Results
The development of radiotherapy techniques, as well as risk-adapted therapy concepts, resulted in promising outcome regarding tumour control, survival and therapy-related side-effects. It is assumed that proton therapy will be increasingly used for treating children in the future. However, more data have to be collected through multi-institutional registries in order to strengthen the evidence.Conclusion
The development of radiotherapy techniques is beneficial for children in terms of reducing dose exposure. As compared with other modern and highly conformal techniques, particularly proton therapy may achieve high survival rates and tumour control rates while decreasing the risk for side-effects. However, clinical evidence for modern radiotherapy techniques is still limited today. An optimal patient triaging with the selection of the most appropriate radiation technique for each individual patient will be an important goal for the future. 相似文献17.
M.S. Iqbal G. Vashisht R. McMenemin P. Atherton F. McDonald T. Simmons A. Bradshaw J. Kovarik H. Turnbull L. Dodd P. Mulvenna A. Greystoke 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):e1-e10
Aims
Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.Materials and methods
One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan–Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.Results
In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.Conclusion
Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial. 相似文献18.
M. Arunsingh S. Vaidyanathan K.E. Dyker M. Sen A.F. Scarsbrook R.J.D. Prestwich 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(4):212-218
Aim
There are few data to inform on the use of response assessment 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following radical radiotherapy without chemotherapy for head and neck squamous cell carcinoma (HNSCC). This retrospective study evaluated the accuracy of PET-CT in HNSCC following radical radiotherapy.Materials and methods
In total, 138 patients with HNSCC treated with radical radiotherapy without chemotherapy who underwent a baseline and response assessment FDG PET-CT were identified. FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes.Results
The median follow-up was 26 months. FDG-avid disease at baseline was present for the primary site and lymph nodes in 118 and 86 patients, respectively. With regard to the primary tumour, the negative predictive value (NPV) of a complete metabolic response (CMR) was 95%; the positive predictive value (PPV) of equivocal uptake and a positive scan were 6% and 82%, respectively. The likelihood ratios for a CMR, equivocal and positive scans of the primary site were 0.19, 0.22, 14.8, respectively. With regard to lymph node disease, the NPV of a CMR was 91%, the PPV of equivocal uptake and a positive scan were 33% and 88%, respectively. Likelihood ratios for lymph node disease for CMR, equivocal and positive scans were 0.19, 0.97 and 15.1, respectively.Conclusion
Compared with the accuracy reported in the literature following chemoradiotherapy, response assessment FDG PET-CT following radical radiotherapy without chemotherapy had a similarly high NPV, whereas the PPV following a positive scan was higher. 相似文献19.
Sara Gagno Mario Rosario D’Andrea Mauro Mansutti Chiara Zanusso Fabio Puglisi Eva Dreussi Marcella Montico Paola Biason Erika Cecchin Donatella Iacono Stefania Russo Marika Cinausero Silvana Saracchini Giampietro Gasparini Donata Sartori Mario Bari Elena Collovà Rosa Meo Giuseppe Toffoli 《Clinical breast cancer》2019,19(2):137-145.e4
Introduction
Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival.Patients and Methods
Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility.Results
Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor–4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively.Conclusion
In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management. 相似文献20.