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    Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial. Chen Yun,Ye Jinjun,Zhu Zhengfei,Zhao Weixin,Zhou Jialiang,Wu Chaoyang,Tang Huarong,Fan Min,Li Ling,Lin Qin,Xia Yi,Li Yunhai,Li Jiancheng,Jia Huixun,Lu Saiquan,Zhang Zhen,Zhao Kuaile Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS:Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS:Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue ( < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis ( < .05). CONCLUSION:The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC. 10.1200/JCO.18.02122
    The Landmark Series: Multimodal Therapy for Esophageal Cancer. Demarest Caitlin T,Chang Andrew C Annals of surgical oncology INTRODUCTION:Esophagectomy is the mainstay of treatment for patients with resectable esophageal cancer, and chemotherapy and chemoradiation have become essential adjuncts to improve survival. Controversy remains regarding the optimal perioperative therapy. METHODS:This review focuses on three landmark, randomized, controlled trials that have greatly influenced esophageal cancer management and established chemotherapy and chemoradiotherapy as standard of care: Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial (MAGIC); The United Kingdom Medical Research Council Esophageal Cancer Trial (OEO2); and Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS). RESULTS:The findings from these landmark studies are reviewed and summarized. CONCLUSION:Chemotherapy regimens are heterogeneous but centered around platinum-based therapy and should be included in the management for all appropriate patients. Ongoing and future studies will further delineate the roles of various chemo- and chemoradiotherapy regimens and also will investigate the promising area of immunotherapy in the treatment of esophageal cancer. 10.1245/s10434-020-09565-5
    Preoperative cisplatin, fluorouracil, and docetaxel with or without radiotherapy after poor early response to cisplatin and fluorouracil for resectable oesophageal adenocarcinoma (AGITG DOCTOR): results from a multicentre, randomised controlled phase II trial. Barbour A P,Walpole E T,Mai G T,Barnes E H,Watson D I,Ackland S P,Martin J M,Burge M,Finch R,Karapetis C S,Shannon J,Nott L M,Varma S,Marx G,Falk G L,Gebski V,Oostendorp M,Wilson K,Thomas J,Lampe G,Zalcberg J R,Simes J,Smithers B M, Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. PATIENTS AND METHODS:Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). RESULTS:Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. CONCLUSIONS:EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. TRIAL REGISTRATION:ACTRN12609000665235. 10.1016/j.annonc.2019.10.019
    Cancer Statistics, 2021. Siegel Rebecca L,Miller Kimberly D,Fuchs Hannah E,Jemal Ahmedin CA: a cancer journal for clinicians Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers. 10.3322/caac.21654
    Oesophageal cancer. Lagergren Jesper,Smyth Elizabeth,Cunningham David,Lagergren Pernilla Lancet (London, England) Oesophageal cancer is a clinically challenging disease that requires a multidisciplinary approach. Extensive treatment might be associated with a considerable decline in health-related quality of life and yet still a poor prognosis. In recent decades, prognosis has gradually improved in many countries. Endoscopic procedures have increasingly been used in the treatment of premalignant and early oesophageal tumours. Neoadjuvant therapy with chemotherapy or chemoradiotherapy has supplemented surgery as standard treatment of locally advanced oesophageal cancer. Surgery has become more standardised and centralised. Several therapeutic alternatives are available for palliative treatment. This Seminar aims to provide insights into the current clinical management, ongoing controversies, and future needs in oesophageal cancer. 10.1016/S0140-6736(17)31462-9
    Is there a future for EGFR targeted agents in esophageal cancer? Ilson D H Annals of oncology : official journal of the European Society for Medical Oncology 10.1093/annonc/mdy135
    Oesophageal cancer. Smyth Elizabeth C,Lagergren Jesper,Fitzgerald Rebecca C,Lordick Florian,Shah Manish A,Lagergren Pernilla,Cunningham David Nature reviews. Disease primers Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and is highly prevalent in the East, East Africa and South America. OAC is more common in developed countries than in developing countries. Preneoplastic lesions are identifiable for both OSCC and OAC; these are frequently amenable to endoscopic ablative therapies. Most patients with oesophageal cancer require extensive treatment, including chemotherapy, chemoradiotherapy and/or surgical resection. Patients with advanced or metastatic oesophageal cancer are treated with palliative chemotherapy; those who are human epidermal growth factor receptor 2 (HER2)-positive may also benefit from trastuzumab treatment. Immuno-oncology therapies have also shown promising early results in OSCC and OAC. In this Primer, we review state-of-the-art knowledge on the biology and treatment of oesophageal cancer, including screening, endoscopic ablative therapies and emerging molecular targets, and we discuss best practices in chemotherapy, chemoradiotherapy, surgery and the maintenance of patient quality of life. 10.1038/nrdp.2017.48