A B S T R AC T BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. METHODS We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. RESULTS From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy–surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy–surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy– surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy–surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P = 0.003). CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.)

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Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

Background Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. Methods Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. Results Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who c...

/pdf/a-comparison-of-multimodal-therapy-and-surgery-for-3cbymnzr3y.pdf

A comparison of multimodal therapy and surgery for esophageal adenocarcinoma.

ContextCarcinoma of the esophagus traditionally has been
treated by surgery or radiation therapy (RT), but 5-year overall
survival rates have been only 5% to 10%. We previously reported
results of a study conducted from January 1986 to April 1990 of
combined chemotherapy and RT vs RT alone when an interim analysis
revealed significant benefit for combined therapy.ObjectiveTo report the long-term outcomes of a previously
reported trial designed to determine if adding chemotherapy during RT
improves the survival rate of patients with esophageal carcinoma.DesignRandomized controlled trial conducted 1985 to 1990 with
follow-up of at least 5 years, followed by a prospective cohort study
conducted between May 1990 and April 1991.SettingMulti-institution participation, ranging from tertiary
academic referral centers to general community practices.PatientsPatients had squamous cell or adenocarcinoma of the
esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a
Karnofsky score of at least 50.InterventionsCombined modality therapy (n=134):
50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the
first day of weeks 1, 5, 8, and 11, and fluorouracil, 1
g/m2 per day by continuous infusion on the first 4 days of
weeks 1, 5, 8, and 11. In the randomized study, combined therapy was
compared with RT only (n=62): 64 Gy in 32 fractions
over 6.4 weeks.Main Outcome MeasuresOverall survival, patterns of failure, and
toxic effects.ResultsCombined therapy significantly increased overall survival
compared with RT alone. In the randomized part of the trial, at 5 years
of follow-up the overall survival for combined therapy was 26% (95%
confidence interval [CI], 15%-37%) compared with 0% following RT.
In the succeeding nonrandomized part, combined therapy produced a
5-year overall survival of 14% (95% CI, 6%-23%). Persistence of
disease (despite therapy) was the most common mode of treatment
failure; however, it was less common in the groups receiving combined
therapy (34/130 [26%]) than in the group treated with RT only (23/62
[37%]). Severe acute toxic effects also were greater in the combined
therapy groups. There were no significant differences in severe late
toxic effects between the groups. However, chemotherapy could be
administered as planned in only 89 (68%) of 130 patients (10% had
life-threatening toxic effects with combined therapy vs 2% in the RT
only group).ConclusionCombined therapy increases the survival of
patients who have squamous cell or adenocarcinoma of the esophagus,
T1-3 N0-1 M0, compared with RT alone.

https://jamanetwork.com/journals/jama/articlepdf/189737/JOC81619.pdf

Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group.

The use of various transgenic mouse models and analysis of human tumour biopsies has shown that bone marrow-derived myeloid cells, such as macrophages, neutrophils, eosinophils, mast cells and dendritic cells, have an important role in regulating the formation and maintenance of blood vessels in tumours. In this Review the evidence for each of these cell types driving tumour angiogenesis is outlined, along with the mechanisms regulating their recruitment and activation by the tumour microenvironment. We also discuss the therapeutic implications of recent findings that specific myeloid cell populations modulate the responses of tumours to agents such as chemotherapy and some anti-angiogenic therapies.

The role of myeloid cells in the promotion of tumour angiogenesis

\n \n \n Up to 50% of patients with esophageal cancer have a pathologically complete response after neoadjuvant chemoradiotherapy (nCRT) plus surgery. An active surveillance strategy may be feasible in patients with a complete clinical response (cCR) after nCRT. The aim of this study was to perform a meta-analysis using data of individual patients that underwent active surveillance with surgery for recurrent disease versus standard surgery after nCRT.\n \n \n \n A systematic search was performed in Embase, Medline, Web of Science, Scopus and Cochrane from inception to February 2020. Studies were sought that reported on overall survival and recurrence rates in patients with cCR after nCRT that underwent active surveillance versus standard surgery. Authors were contacted to supply individual patient data. Pooled hazard ratio (HR) comparing survival outcomes and distant dissemination rates (DDR) between patients with cCR undergoing active surveillance or standard surgery were estimated using a random-effect meta-analysis. Cumulative incidence of locoregional recurrences in active surveillance were assessed using a Cox Frailty model.\n \n \n \n Seven studies including 788 patients (256 active surveillance and 532 surgery) were identified. All authors provided anonymized patient data. Pooled two- and five-year overall-survival was 75% and 58% for active surveillance and 76% and 60% for standard surgery with a pooled HR of 1.04 (95%CI:0.73–1.49) (Figure 1). Two-years DDR was 18% and 19% for active surveillance and standard surgery, respectively (HR 1.10,95%CI:0.75–1.63). Locoregional recurrence rate necessitating esophagectomy in patients undergoing active surveillance was 24% at one year, 33% at two years and 38% at five years. Active surveillance patients undergoing postponed surgery had R0 in 91% of cases.\n \n \n \n Overall survival is comparable in patients undergoing active surveillance with postponed surgery compared to standard surgery after neoadjuvant chemoradiation. Distant dissemination rate is also comparable between both groups. During active surveillance, local regrowths developing after two years are rare. Although these data support an active surveillance strategy, randomized trials have to be completed before an active surveillance strategy can be actively proposed to patients with esophageal cancer.\n

http://academic.oup.com/dote/article-pdf/33/Supplement_1/doaa087.50/33743744/doaa087.50.pdf

257 chemoradiotherapy followed by active surveillance versus surgery for esophageal cancer: a systematic review and individual patient data meta-analysis

Trans-Balloon Visualisation During Dilatation (TBVD) of Oesophageal Strictures: a Novel Innovation

Exposure to lipopolysaccharide elicits vascular endothelial growth factor production by macrophages and tumour cells

Proposal for a standardised classification system for audit of induction of labour.

Background
A web site Is a valuable shop window for any medical unit with something to sell or something to say.

Thomas N. Walsh

Papers

257 chemoradiotherapy followed by active surveillance versus surgery for esophageal cancer: a systematic review and individual patient data meta-analysis

Trans-Balloon Visualisation During Dilatation (TBVD) of Oesophageal Strictures: a Novel Innovation

Exposure to lipopolysaccharide elicits vascular endothelial growth factor production by macrophages and tumour cells

Proposal for a standardised classification system for audit of induction of labour.

Designing a medical Web site.