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

The effect of cholecystectomy on plasma cholecystokinin

Targeting therapy for esophageal cancer in patients aged 70 and over.

The motility of the vagally denervated transposed stomach after oesophagectomy was examined by ambulatory gastric manometry and videofluoroscopy. Two groups of subjects were studied. Group 1 comprised ten patients who had undergone oesophagectomy 6-12 months previously and group 2 consisted of six normal control subjects. Studies were performed on fasting and fed subjects, and following injection of erythromycin 8 mg/kg. No distinguishable manometric wave activity was seen in either group while fasting. Feeding generated a measurable wave pattern in the patient group only. A significant increase in the mean(s.e.m.) distal wave amplitude was identified afteinfusion of erythromycin in both patients (34.0(15.1) versus 12.2(3.1) mmHg, P<0.05) and controls (15.1(3.4) versus 5.0(0.0) mmHg, P=0.05). The response to erythromycin was more rapid in patients than in controls (mean(s.e.m.) 113(16) versus 377(133) s, P<0.05) and the effect persisted for longer (more than 1 h) in those who had undergone oesophagectomy. Videofluoroscopy confirmed purposeful motility in both the normal and vagally denervated stomach. It is concluded that the transposed stomach is a dynamic conduit. Enhancement of motility was greatest in the denervated stomach, indicative of denervation supersensitivity

Gastric motility following oesophagectomy.

AIMS: To evaluate the impact of umbilical and uterine artery Doppler in the second and third trimester on antenatal course, labor and delivery in a low-risk primigravid population.

METHODS: Prospective recruitment of 1011 low-risk primigravidas with uterine and umbilical artery Doppler assessment at 22-24 weeks and 36 weeks. All mothers and infants were reviewed postnatally with a retrospective analysis of ultrasound and clinical outcome data.

RESULTS: Elevated uterine artery indices were associated with increased rates of threatened miscarriage, higher rates of pre-eclampsia (PET) and a higher incidence of fetal birth weight 95th centile for gestation was associated with statistically higher rates of small-for-gestational age (SGA) infants. Elevated umbilical artery indices were associated with higher rates of induction of labor and a higher incidence of fetal birth weight infants 95th centile for gestation was associated with statistically higher rates of SGA infants.

CONCLUSION: Elevated uterine and umbilical artery indices are associated with higher rates of maternal and fetal disease.

The impact of umbilical and uterine artery Doppler indices on antenatal course, labor and delivery in a low-risk primigravid population.

Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.

Thomas N. Walsh

Papers

The effect of cholecystectomy on plasma cholecystokinin

Targeting therapy for esophageal cancer in patients aged 70 and over.

Gastric motility following oesophagectomy.

The impact of umbilical and uterine artery Doppler indices on antenatal course, labor and delivery in a low-risk primigravid population.

Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.