Dosimetric correlates for acute esophagitis in patients treated with radiotherapy for lung carcinoma

PURPOSE: Acute esophagitis is a common complication of radiotherapy (RT) for non-small-cell carcinoma of the lung. Previous reports have related esophagitis to dosimetric parameters such as the length of the irradiated esophagus, maximal dose, or volume of the organ treated beyond a threshold dose. However, when using oblique beams, a portion of the esophageal circumference may be outside the treated field, resulting in partial esophageal irradiation. Therefore, our aim was to determine whether the irradiated esophageal surface area and/or esophageal volume are predictive of acute esophagitis in relation to other clinical and treatment-related factors. METHODS AND MATERIALS: Complete dose-volume information was gathered for 166 patients receiving definitive RT for Stage I-IIIB non-small-cell carcinoma of the lung at our institution. Seventy-eight patients received chemotherapy (37 before RT and 41 concurrently). All patients were treated to doses of 60-74 Gy (median, 70 Gy) delivered in single daily fractions of 1.8-2.1 Gy. The doses were prescribed to the isocenter without using heterogeneity corrections; however, the doses were corrected to account for lung heterogeneity in this report. Esophageal contrast was used to contour the esophagus from the cricoid to the gastroesophageal junction in each case. Esophagitis was scored according to the Radiation Therapy Oncology Group criteria with Grade 2 or worse considered clinically significant. To determine the importance of the irradiated surface area, the volumetric treatment plan for each patient was prepared for analysis by relating a surface area to each point of the esophagus contour. Spearman's rank correlation was used to correlate the esophagitis score with A(d), where A represents the surface area (in centimeters squared) receiving the dose, d, or greater (in Gray), or V(d), where V represents the volume (in centimeters cubed) receiving d (in Gray). The surface areas studied were A(5)-A(80) or V(5)-V(80) in 5-Gy increments. The clinical parameters studied in univariate analysis included patient age, stage, performance status, use of pretreatment chemotherapy, and use of concurrent chemotherapy. Step-wise regression analysis was then used to determine the statistically significant factors predicting acute esophagitis. RESULTS: Forty-five patients (27%) developed Grade 2 or worse esophagitis, 37 developed Grade 2, 7 Grade 3, and 1 Grade 4. No deaths resulted from this complication. The most statistically significant single parameters for predicting acute esophagitis were A(55), V(60), and the use of concurrent chemotherapy. Age, stage, performance status, and pre-RT chemotherapy had no statistically significant influence on the incidence of acute esophagitis. On logistic regression analysis, A(55) (p < or =0.0005), V(60) (p < or =0.001), and the use of concurrent chemotherapy (p = 0.001) emerged as statistically significant correlates of acute esophagitis. CONCLUSION: The esophageal surface area receiving > or =55 Gy, the esophageal volume receiving > or =60 Gy, and the use of concurrent chemotherapy were the most statistically significant predictive factors for early esophagitis. Adequate dosimetric coverage of the planning target volume remains the goal of RT planning. High values of A(55) and/or V(60) are indicative of the development of acute esophagitis and may indicate a need to explore alternative RT planning options.     

Glycerol-3-phosphate dehydrogenase activity in the red cells of patients with thalassemia

L-alpha-Glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) has been reported to be absent in the erythrocytes of normal adults, but can be found in those of cord blood and of thalassemia major. The aid of this study was to investigate whether there is any relation between GDH and gamma-chain synthesis. Erythrocyte GDH activity was determined on 118 different blood samples. It was undetectable in normal adult erythrocytes and definitely high in cord blood cells (23.6 UI/10(11) RBC). Considerable GDH activity was also noted in patients with thalassemia major (11.0 IU10(11) RBC) as well as in cases with pronounced reticulocytosis (11.4 IU/10(11) RBC). Red cells from beta- thalassemia heterozygotes exhibited moderate but distinct GDH activity (5.2 IU/10(11) RBC). After fractionation into young and old erythrocyte populations, clearly higher GDH activity was found in the younger cells; however, there was no significant correlation with the reticulocyte count. Presence of reticulocytes alone appears insufficient to explain the values obtained in cord blood and the thalassemias, especially heterozygous. Furthermore, no direct correlation between GDH and fetal hemoglobin (HbF) was obtained in cord and thalassemic erythrocytes.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.     

Nurse Practitioner Intervention to improve Postpartum Appointment Keeping in an Outpatient Family Planning Clinic

A nurse practitioner (NP) program to improve postpartum appointment keeping in an outpatient family planning clinic is described and evaluated. The subjects (N = 59) were non-high-risk obstetric patients prescheduled to be seen at 6 weeks postpartum by the NP. Two groups were identified by convenience sampling: Group A (n = 25), the nonintervention group, and Group B (n = 34), the intervention group. Two types of intervention were used: a postpartum telephone call after discharge (n = 11), or a predischarge postpartum visit (n = 23). Results suggest that those in the intervention group were more likely to keep their appointments (p less than .02); only the postpartum visit increased the probability of appointment keeping (p less than .05).     

Modeling positioning uncertainties of prostate cancer external beam radiation therapy using pre-treatment data

Purpose

To investigate the influence of treatment plan data and image guidance (IG) on positioning uncertainty during prostate cancer (PCa) radiotherapy (RT).

Methods

Body mass index (BMI), planning target volume (PTV), bladder volume (BV), and rectal cross section area (RCS) were collected for 267 consecutive PCa patients undergoing daily IGRT. Radiographic isocenter corrections to intra-prostatic fiducials for 12,490 treatment fractions were used to derive random (RE) and systematic (SE) inter-fraction uncertainties for the cardinal axes. These data were used to simulate RE and SE for weekly IG and Action Level (AL)-IG treatment protocols.

Results

SE and RE were 2–5 and 3–4 mm in the cardinal axes, respectively, during simulation of no IG. Without IG, positive correlations (p < 0.01) were noted for (1) anterior-posterior RE vs. RCS and BV and (2) cranio–caudal RE vs. RCS, BV and BMI. The RE increase was 3 mm for the highest quartile of RCS, BV and BMI. Daily IGRT eliminated this relationship. 3D IG corrections of 1 cm or more occured in 27% of treatment fractions and in 97% of patients.

Conclusion

PCa patients with elevated pre-treatment BV, RCS and BMI have increased inter-fractionation positioning uncertainty and appear the primary candidates for daily IGRT.     

Identification of material with paternal HLA antigen immunoreactivity from purported circulating immune complexes in patients with gestational trophoblastic neoplasia

Circulating immune complex(es) (CIC) have been shown to rise progressively only when patients with hydatidiform molar pregnancy enter gonadotropin-documented remission. The CIC in 3 patients with gestational trophoblastic neoplasia (GTN)--1 with hydatidiform mole and 2 with choriocarcinoma--were characterized. Their clinical course was monitored by serial antigen-nonspecific polyethylene glycol (PEG) 6000-CIC assay and simultaneous human chorionic gonadotropin (HCG) assay from presentation until sustained gonadotropin-documented remission. As serial HCG progressively decreased to normal following surgical or chemotherapeutic reduction in tumor burden, PEG-CIC concurrently rose. Serum obtained at or near peak PEG-CIC levels was precipitated by 3.75% PEG 6000 and fractionated by column chromatography on Sephadex G-200 (exclusion limit, greater than 600,000 mol wt) in glycine-HCl and 1 M NaCl buffer at pH 2.8. None of the 5 elution fractions obtained from the 3 patients contained HCG or anti-HCG activity. However, in the hydatidiform molar patient, fractions 1 through 3 (mol wt greater than 67,000--and containing immunoglobulin) were shown to competitively inhibit complement-dependent antibody lysis on 1 of 4 paternal HLA haplotype (AW32) targets. In 2 of the 3 patients studied, low-molecular-weight fractions (not containing immunoglobulin) significantly inhibited reference anti-HLA binding of antisera directed against only 1 of 4 paternal HLA haplotypes. The immunospecificity of this inhibition was confirmed by criss-cross control assays in which elution fractions obtained from both of these patients were tested for inhibition of lymphocytolysis of both sets of paternal lymphocytes. None of these fractions were immunoreactive to maternal HLA haplotypes. Further analysis of serum from the hydatidiform molar patient revealed that no free complement-fixing antibody against paternal antigens could be found by conventional screening assays in unfractionated patient sera. Three of 4 paternal HLA antigens or non-complement-fixing anti-HLA immunoglobulin was detected in unfractionated pretreatment, treatment, and remission sera of the hydatidiform molar patient. Only in this patient's remission sera was unbound AW32 antigen or non-complement-fixing anti-AW32 antibody detected. These data demonstrate the successful characterization of at least 1 specific antigen fractionated from a tumor-associated immune complex. The implication that some patients with GTN may recognize and react to immunogenic paternal HLA antigens as part of their successful response to therapy for trophoblastic tumor is discussed.