Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma

PURPOSE: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy (RT) alone. The goal of this study was to update our experience of high-dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT), for such patients. METHODS AND MATERIALS: Between 1984 and 2003, 38 patients with Stage I and Stage II adenocarcinoma of the endometrium considered high operative risk received RT as the primary treatment. The median age was 74.1 years. Before 1996, the local extent of the disease was assessed by an examination under anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter. Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy, typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was 42 Gy. RESULTS: At a median follow-up of 57.5 months for patients at risk, 11 patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%) distantly, and 1 patient (3%) locally and distantly. Local failure was established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and higher grade were both associated with increased failure rate. The 15-year disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42% for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade II and III combined (p = 0.0254). Patients with Stage I disease established by MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of 100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3 Grade III or IV. CONCLUSION: Medically inoperable Stage I endometrial carcinoma may be safely and effectively treated with HDRB as the primary therapy. In selected Stage I patients, our results are equivalent to that of surgery. We believe that the alternative option of HDRB as the primary therapy for selected Stage I endometrial carcinoma, even in patients with low operative risks, needs further evaluation.     

High-dose-rate Rotte "Y" applicator brachytherapy for definitive treatment of medically inoperable endometrial cancer: 10-year results

PURPOSE: To assess the intermediate clinical outcomes of medically inoperable patients with endometrial cancer treated with definitive Rotte "Y" applicator high-dose-rate brachytherapy (HDRB) over a 10-year period. METHODS AND MATERIALS: Forty-nine inoperable patients were treated with HDRB from 1997 to 2007. Forty three (84%) were markedly obese (body mass index >35 kg/m(2)). Thirty-one patients (63.3%) underwent two-dimensional treatment planning, whereas 18 patients (36.7%) underwent three-dimensional treatment planning. Thirty five of the patients (71.4%) were first treated with external beam radiotherapy (EBRT). For patients receiving EBRT in addition to HDRB, the median Y-applicator dose was 20 Gy in 5 fractions; for patients receiving HDRB alone it was 35 Gy in 5 fractions. All patients received two Y-applicator treatments per day. RESULTS: Median follow-up time for all patients was 33 months. Acute HDRB toxicities were limited to Grade 1 and 2 occurring in 5 patients. One patient had a myocardial infarction. Four patients had late Grade 2 or 3 toxicity. Three patients had local recurrence (median time to recurrence, 16 months). The 3- and 5-year actuarial cause-specific survival rates were 93% and 87%, respectively; the overall survival rate was 83% and 42%, respectively, at 3 and 5 years. CONCLUSIONS: Twice-daily HDRB using a Y-applicator is a well-tolerated and efficacious regimen for the definitive treatment of medically inoperable patients with early-stage endometrial cancer. The recent incorporation of three-dimensional treatment planning has the potential to further decrease treatment morbidities.     

Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer

PURPOSE: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer. METHODS AND MATERIALS: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The alpha/beta ratios were estimated via a proportional hazards model stratified by risk severity and institution. RESULTS: The alpha/beta ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, infinity Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; alpha/beta ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up matured (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision. CONCLUSIONS: This study supports the concept that the alpha/beta ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.     

Modeling normal tissue complication probability from repetitive computed tomography scans during fractionated high-dose-rate brachytherapy and external beam radiotherapy of the uterine cervix

PURPOSE: To calculate the normal tissue complication probability (NTCP) of late radiation effects on the rectum and bladder from repetitive CT scans during fractionated high-dose-rate brachytherapy (HDRB) and external beam radiotherapy (EBRT) of the uterine cervix and compare the NTCP with the clinical frequency of late effects. METHODS AND MATERIALS: Fourteen patients with cancer of the uterine cervix (Stage IIb-IVa) underwent 3-6 (mean, 4.9) CT scans in treatment position during their course of HDRB using a ring applicator with an Iridium stepping source. The rectal and bladder walls were delineated on the treatment-planning system, such that a constant wall volume independent of organ filling was achieved. Dose-volume histograms (DVH) of the rectal and bladder walls were acquired. A method of summing multiple DVHs accounting for variable dose per fraction were applied to the DVHs of HDRB and EBRT together with the Lyman-Kutcher NTCP model fitted to clinical dose-volume tolerance data from recent studies. RESULTS: The D(mean) of the DVH from EBRT was close to the D(max) for both the rectum and bladder, confirming that the DVH from EBRT corresponded with homogeneous whole-organ irradiation. The NTCP of the rectum was 19.7% (13.5%, 25. 9%) (mean and 95% confidence interval), whereas the clinical frequency of late rectal sequelae (Grade 3-4, RTOG/EORTC) was 13% based on material from 200 patients. For the bladder the NTCP was 61. 9% (46.8%, 76.9%) as compared to the clinical frequency of Grade 3-4 late effects of 14%. If only 1 CT scan from HDRB was assumed available, the relative uncertainty (standard deviation or SD) of the NTCP value for an arbitrary patient was 20-30%, whereas 4 CT scans provided an uncertainty of 12-13%. CONCLUSION: The NTCP for the rectum was almost consistent with the clinical frequency of late effects, whereas the NTCP for bladder was too high. To obtain reliable (SD of 12-13%) NTCP values, 3-4 CT scans are needed during 5-7 fractions of HDRB treatments.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Urethral stricture following high dose rate brachytherapy for prostate cancer

Purpose

To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma.

Methods and materials

Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0.

Results

At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008).

Conclusions

BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.     

Results of high dose-rate brachytherapy boost before 2D or 3D external beam irradiation for prostate cancer

Background and purpose

To evaluate biochemical control and treatment related toxicity of patients with localized adenocarcinoma of the prostate treated with high dose-rate brachytherapy (HDRB) combined with conventional 2D or 3D-conformal external beam irradiation (EBI).

Material and methods

Four-hundred and three patients treated between December 2000 and March 2004. HDRB was delivered with three fractions of 5.5-7 Gy with a single implant, followed by 45 Gy delivered with 2D or 3D conformal EBI.

Results

The median follow-up was 48.4 months. Biochemical failure (BF) occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. Mean time to relapse was 13 and 26 months, respectively. The 5-year BF free survival using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively; using Phoenix criteria, 92.4%, 88.0% and 85.3%, respectively. The only predictive factor of BF in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules detected by digital palpation, and patients younger than 60 years presented a higher chance of failure using Phoenix criteria only.

Conclusions

Treatment scheme is feasible and safe with good efficacy.     

External beam radiotherapy plus single-fraction high dose rate brachytherapy in the treatment of locally advanced prostate cancer

Purpose

To evaluate the efficacy and toxicity of external beam radiation therapy (EBRT) plus high-dose-rate brachytherapy (HDRB) as a boost in patients (pts) with intermediate or high-risk prostate cancer.

Methods and materials

From 2002 to July 2012, 377 pts with a diagnosis of intermediate or high-risk prostate cancer were treated with EBRT plus HDRB. Median patient age was 66 years (range, 41–86). Most patients (347 pts; 92%) were classified as high-risk (stage T2c–T3, or PSA > 20 ng/mL, or GS ? 8), with 30 patients (8%) considered intermediate risk. All patients underwent EBRT at a prescribed dose of 60.0 Gy (range, 45–70 Gy) to the prostate and seminal vesicles. A total of 120 pts (31%) received a dose of 46 Gy (45–50 Gy) to the true pelvis. All pts received a single-fraction 9 Gy (9–15 Gy) HDR boost. Most patients (353; 94%) were prescribed complete androgen deprivation therapy (ADT). Overall survival (OS), cause-specific survival (CSS), and biochemical relapse-free survival (BRFS) rates were calculated. In the case of BRFS, patients with <26 months of follow-up (n = 106) were excluded to minimize the impact of ADT.

Results

The median follow-up for the entire sample was 50 months (range, 12–126), with 5-year actuarial OS and CSS, respectively, of 88% (95% confidence interval [CI]: 84–92) and 98% (95% CI: 97–99). The 5-year BRFS was 91% (95% CI: 87–95) in the 271 pts with ?26 months (median, 60 months) of follow-up. Late toxicity included grade 2 and 3 gastrointestinal toxicity in 17 (4.6%) and 6 pts (1.6%), respectively, as well as grades 2 and 3 genitourinary toxicity in 46 (12.2%) and 3 pts (0.8%), respectively.

Conclusion

These long-term outcomes confirm that EBRT plus a single-fraction HDRB boost provides good results in treatment-related toxicity and biochemical control. In addition to the excellent clinical results, this fractionation schedule reduces physician workload, treatment-related expenses, patient discomfort and risks associated with anaesthesia. We believe these findings support the use of single-fractionation boost techniques.     

原发中枢神经系统淋巴瘤40例治疗与预后分析

目的 比较不同治疗方法对原发中枢神经系统淋巴瘤患者的有效性及安全性.方法 收集40例原发中枢神经系统淋巴瘤患者,分为3组,其中单纯手术组10例、手术联合化疗组15例、手术联合放化疗组15例,对3组进行生存分析比较.结果 随访7~53个月,中位生存时间手术联合放化疗组(45个月)和手术联合化疗组(30个月)高于单纯手术组(17个月),差异均有统计学意义(P均<0.05).3 a生存率手术联合放化疗组(72.2%)高于手术联合化疗组(40.8%)和单纯手术组(27.3%,P均<0.05).结论 手术联合放化疗可有效治疗原发中枢神经系统淋巴瘤,且患者耐受性好.     

Presurgery chemotherapy (CT) in locally advanced bladder carcinoma: a feasible and possibly effective approach

In October 1984, a prospective pilot study aiming to evaluate the feasibility and to preliminarily test the efficacy of the chemotherapy--surgery sequence in locally advanced bladder carcinoma was started at our institutions. Chemotherapy consisted of adriamycin 50 mg mq-2 and cisplatin 50 mg mq-2 on day 1 and fluorouracil 500 mg mq-2 and teniposide 100 mg mq-2 on days 1 and 8; chemotherapy was repeated every 3 weeks for three cycles and followed by surgery (radical cystectomy; TUR if radical surgery medically contraindicated). The characteristics of the 28 patients so far treated include: T3b in 26 patients, local relapse after surgery in two, nodal metastases in seven. Twenty-five patients were male and three female, median age was 61 yr (range 42-75). Clinical response following chemotherapy was: complete remission (CR) in five patients, partial remission (PR) in 15, stable disease (SD) in three, progression (PRO) in two. Three patients are not evaluable. Treatment was moderately well tolerated. Thirteen patients underwent radical surgery, three exploratory surgery, three TUR; refusal in three patients, early death in two, too early in one. No evidence of disease was found in the surgical specimen of five patients (three CR, two PR), microscopic residual disease in four PR patients, gross residual disease in 11 patients (one CR, six PR, two SD, two PRO). Actuarial median survival (all 28 patients) is 45% at 36 months. These preliminary results suggest that the combination of chemotherapy and surgery is feasible and may be effective in these poor prognosis patients.     

Evaluation of clinical utility of BTC-2000 for measuring soft tissue fibrosis

PURPOSE: To evaluate whether mechanical tissue parameters, specifically laxity (in millimeters) and energy absorption (millimeters of mercury multiplied by millimeters) as measured by the BTC-2000, could discriminate levels of fibrosis severity among patients treated for extremity soft tissue sarcoma by surgery alone; preoperative radiotherapy (RT) and surgery; and surgery followed by postoperative RT. METHODS AND MATERIALS: A total of 41 patients were treated for extremity soft tissue sarcoma by surgery alone (n = 11); preoperative RT (50 Gy in 2-Gy daily fractions) and surgery (n = 15); and surgery followed by postoperative RT (66 Gy in 2-Gy daily fractions; n = 15). Serial fibrosis measurements were evaluated at equal intervals from the midpoint of the surgical incision along the length of the incision. On the basis of the average of these measurements, differences among the three groups were analyzed using analysis of variance. RESULTS: Pair-wise statistically significant differences were found among the three treatment groups for both laxity and energy absorption as determined by the average of all measurements. The treatment difference remained statistically significant even after adjusting for differences based on the untreated contralateral limb and anatomic site (p <0.001 and p = 0.002 for laxity and energy absorption, respectively). CONCLUSION: The biomechanical tissue parameters of laxity and energy absorption discriminated fibrosis severity in patients treated with different RT doses. The BTC-2000 may provide a useful quantitative measure of soft tissue fibrosis.     

Treatment results and prognostic factors in inoperable carcinoma of the cervix treated with external plus high dose brachytherapy

Patients with inoperable carcinoma of the cervix treated with external plus high dose rate brachytherapy (HDRB), between 1988 and 1995 were evaluated retrospectively. According to stage, 5 year survival rates were 67.3% in stage IIb and 52.6% in stage III (P = 0001) and disease free survival (DFS) rates were 54.0% in stage IIb and 43.9% in stage III (P = 0.01). The following parameters were studied: age; stage; external beam dose; brachytherapy dose; total dose to point A; tumor mass; tumor response rate; bilateral or unilateral invasion of parametria in stage IIb; and bilateral or unilateral invasion of pelvic wall in stage IIIb; and the existence of hydronephrosis. The only significant parameter of 5 year survival and local control was tumor mass (P = 0.003).     

Organ-preserving surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors

Organ-preserving surgery is generally accepted when renal cell carcinoma (RCC) occurs in a solitary kidney or in both kidneys. Over a 12-year period, 238 patients underwent surgery for RCC at our hospital; 15 (6.3%) of these underwent organ-preserving procedures. Nine of ten patients with disease in a solitary kidney are alive without evidence of tumor (four more than 5 years postoperatively and five from 2 to 4 years). Six patients had bilateral disease, three of whom are alive at 2, 2, and 3 years, and three of whom died at 4, 5, and 9 years.     

The role of adjuvant surgery in the combined modality therapy of small-cell bronchogenic carcinoma after a chemotherapy-induced partial remission

Twenty-six patients with a limited-disease presentation of small-cell bronchogenic carcinoma (SCBC) had surgery after achieving a partial remission with three cycles of chemotherapy. Persistent SCBC was found in 15 patients (58%), non-small-cell bronchogenic carcinoma (NSCBC) in six patients (23%), and no malignancy in five patients (19%). Twelve patients have died since surgery. Tumor-node-metastasis (TNM) staging prior to or after chemotherapy was not predictive of outcome, but an N0 status found at pathological examination of the surgical specimen was predictive of long-term survival. Median survival for this group of patients was 25 months. Adjuvant surgery is feasible and may be beneficial.     

Dysgerminoma of the ovary: A retrospective study

A retrospective analysis of 22 patients with ovarian dysgerminoma who were treated between 1980 and 1987 was carried out. The median age at presentation was 24.5 years. A total of 15 patients were in stage I, one patient was in stage II and six patients were in stage III. Bilateral ovarian involvement was present in four patients. Conservative surgery was carried out in nine patients and 11 patients underwent radical surgery. Two patients had biopsy only. Fourteen patients received adjuvant radiotherapy and three patients received salvage radiation for recurrent disease. The 10-year actuarial survival rate was 81.8%. All 15 patients in stage I were alive and disease-free at a median follow-up of 125 months. Four patients (one in stage II and three in stage III) died of progressive or recurrent abdominopelvic disease. Pelvic recurrence occurred after conservative surgery in two patients in stage IA who had a tumour size greater than 10 cm, but they were salvaged with radical surgery, chemotherapy and radiotherapy. There were seven patients aged 20 years or less. All were alive and disease-free at a median follow-up of 127 months.     

Presurgery chemotherapy (CT) in locally advanced bladder carcinoma: a feasible and possibly effective approach

In October 1984, a prospective pilot study aiming to evaluate the feasibility and to preliminarily test the efficacy of the chemotherapy-surgery sequence in locally advanced bladder carcinoma was started at our institutions. Chemotherapy consisted of adriamycin 50 mg mq⁻² and cisplatin 50 mg mq⁻² on day 1 and fluorouracil 500 mg mq⁻² and teniposide 100 mg mq⁻² on days 1 and 8; chemotherapy was repeated every 3 weeks for three cycles and followed by surgery (radical cystectomy; TUR if radical surgery medically contraindicated). The characteristics of the 28 patients so far treated include: T3b in 26 patients, local relapse after surgery in two, nodal metastases in seven. Twenty-five patients were male and three female, median age was 61 yr (range 42–75). Clinical response following chemotherapy was: complete remission (CR) in five patients, partial remission (PR) in 15, stable disease (SD) in three, progression (PRO) in two. Three patients are not evaluable. Treatment was moderately well tolerated. Thirteen patients underwent radical surgery, three exploratory surgery, three TUR; refusal in three patients, early death in two, too early in one. No evidence of disease was found in the surgical specimen of Five patients (three CR, two PR), microscopic residual disease in four PR patients, gross residual disease in 11 patients (one CR, six PR, two SD, two PRO). Actuarial median survival (all 28 patients) is 45% at 36 months. These preliminary results suggest that the combination of chemotherapy and surgery is feasible and may be effective in these poor prognosis patients.     

Granulosa cell tumor of the ovary: A study of 18 cases

In a study of 18 patients diagnosed with ovarian granulosa cell tumor between 1961 and 1992, clinical and pathologic findings were evaluated. Of the 18 patients, 15 (83.3%) were diagnosed in Stage I and three (16.7%) in Stage III or IV. Six patients (33.3%) underwent conservative surgery and in 12 (66.7%) total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. At follow-up three patients (16.6%) had died of disease, three, 16 and 288 months, respectively, after initial surgery. The actuarial 5-year survival rate for Stage I was 100%, while that for Stages III and IV combined was 33.3% (P < 0.05). It is concluded that for patients with Stage IA, unilateral oophorectomy seems to be adequate treatment and for those with more than Stage IA, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy. Postoperative adjuvant chemotherapy is advocated for patients in whom spread of tumor beyond the ovaries has occurred. © Wiley-Liss, Inc.     

Adjuvant chemotherapy in the management of primary malignant melanoma.

In a prospective randomized study, the effect of chemotherapy (either systemic or combined intraarterial and systemic) was studied in 117 patients undergoing a curative resection of Clark's level III, IV or V malignant melanoma. Systemic chemotherapy was started one month after surgery one week courses with an I.V. injection of Vinblastin 6 mg/m2, Thiotepa 6 mg/m2, Rufocromomycine 60 microgram/m2, Methotrexate 15 mg/m2 on day one with procarbazine 30 mg/m2 orally daily were given every other week for three months and later every four weeks. Intraarterial chemotherapy of DTIC 80 mg/kg day for ten days was given 28 days prior to surgery. 65 patients with limb malignant melanoma were treated either by surgery only (27 patients), or by systemic chemotherapy (23 patients) or by preoperative intraarterial chemotherapy and systemic chemotherapy (15 patients): 52 patients with non limb malignant melanoma were treated either by surgery only (28 patients) or by systemic chemotherapy (24 patients). We drew curves of disease free survival following surgery and studied the levelling off of the curves, 24 months after surgery 65% of the patients treated by surgery alone were alive and free of disease whereas 81% of the patients treated by surgery and chemotherapy were alive and free of disease (p less than 0.05) suggesting a possible benefit of adjuvant chemotherapy. Intraarterial preoperative chemotherapy has not proved of additional benefit to date.     

Increased serum VEGF in 13 children with Wilms' tumour falls after surgery but rising levels predict poor prognosis

Vascular endothelial cell growth factor (VEGF, a potent endothelial cell mitogen in vitro) may be important in tumour development and its spread in vivo. In this preliminary study, we tested the hypotheses that (i) raised serum levels in Wilms' tumour fall after surgery, and (ii) rising levels predict adverse outcome. Serum VEGF was measured (ELISA) in 13 children about to undergo surgery, and serially on the following day, a week later, and finally 3-6 months after surgery. A simple follow-up at 6 months was also performed. The control group was 60 healthy adults. Before surgery, the median (inter-quartile range) VEGF in the children was 20 ng/ml (10.4-70.5) and was 1 ng/ml (0.5-4.0) in the adults. This difference is statistically highly significant (P=0.0001). After surgery, levels in the children fell significantly to 1.3 ng/ml (0.5-7.95) the following day and to 1.9 ng/ml (0.5-5.0) the following week (P<0.001, ANOVA). Six months after surgery, three of the children had died. A level of >10 ng/ml measured 3 months after surgery correctly identified all three deaths: levels were 1.3 ng/ml (0.5-1.9) in the survivors and were 20.0 ng/ml (15-104) in those who died. These data indicate a rapid reduction in raised VEGF following surgery for Wilms' tumour, but that rising levels predict poor prognosis.     

Combined radiotherapy and pre-radiation chemotherapy with cisplatin and 5-fluorouracil for advanced esophageal carcinoma. II. Clinical evaluation in cases with higher than T2 stage

Thirteen patients with previously untreated advanced squamous cell carcinoma of the esophagus were treated with pre-radiation chemotherapy followed by radiation therapy. The chemotherapy consisted of two or three cycles of Cisplatin and 120 hour continuous infusion of 5-Fluorouracil. Three patients showed complete response (CR), three partial response (PR), three minor response (MR) and four non-response (NR). The overall response rate was 46%. The predominant side effects were nausea, vomiting and anorexia. Mild or moderate degree of anemia and leukocytopenia were also noticed. However, no serious toxicity was observed. Radiation therapy was administered to eleven of the thirteen patients, excluding one patient who refused it and one patient who died during chemotherapy. In two of the eleven cases, however, radiotherapy was discontinued because of MR, and surgery was performed. In one additional case, post-radiotherapy surgery was performed. One of these three cases received curative esophagectomy. After definitive treatment, CR was obtained in 54% (7 of 13), PR in 15% (2 of 13), MR in 15% and NR in 15%. The non-effective patients (PR + MR + NR) died within nine months after the initiation of treatment. Two of the CR patients later died, one due to local recurrence and another due to aortic-esophageal fistula with no residual cancer discovered at autopsy. The remaining CR patients are still alive and well, after 11.5 to 32 months. Although the follow-up period is yet short, the combination of radiation therapy with pre-radiotherapy chemotherapy appears to be an effective treatment.