Claudia Perez-Tamayo

Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report.

PURPOSE In 1990 we published the results of an intensive 3-week preoperative chemoradiation regimen for locoregional esophageal cancer that suggested improved survival compared with historical controls. We now report the long-term results at a median follow-up of 78.7 months. PATIENTS AND METHODS Forty-three patients with locoregional squamous cell carcinoma or adenocarcinoma of the esophagus or cardia were treated with fluorouracil (5-FU), cisplatin, and bolus vinblastine concurrent with radiation administered over 21 days. Transhiatal esophagectomy was performed on day 42. RESULTS Forty-one patients (95%) completed the preoperative treatment, and 36 (84%) had a potentially curative resection. Ten of 41 (24%) had no tumor in the resected esophagus and nodal tissues (path-negative group). The median survival duration of all 43 patients registered on study was 29 months; 34% were alive at 5 years. By histology, median survival durations were 32 months for 21 adenocarcinoma patients and 23 months for 22 squamous cell patients, with corresponding 5-year survival rates of 34% and 31%, respectively. Analysis of the 36 patients who underwent a potentially curative resection demonstrated median survival durations of 32 and 44 months and 5-year survival rates of 36% and 43%, respectively, for adenocarcinoma and squamous cell histologies. Path-negative (complete response [CR]) patients had a median survival duration of 70 months and 60% were alive at 5 years, while those patients with residual tumor in the resected esophagus had a median survival duration of 26 months and 32% were alive at 5 years (P = .114 by the log-rank test and P = .04 by the Wilcoxon test). CONCLUSION The results of this regimen appear improved over those reported with surgery alone, with an approximate doubling of the 5-year survival rate. Thirty-two percent of patients with residual tumor in the esophageal specimen are long-term survivors, which suggests a benefit from esophagectomy. A randomized trial is in progress to compare this preoperative regimen with immediate surgery.

Treatment planning issues related to prostate movement in response to differential filling of the rectum and bladder

Conventional stimulation for patients with localized prostatic carcinoma often includes opacification of the dose limiting adjacent normal tissues. However, CT-based treatment planning is performed with the bladder and the rectum naturally filled or emptied. These latter conditions more closely approximate those in place at treatment Comparison of these CT-based treatment plans to simulator films taken with the rectum and bladder opacified yielded indirect evidence of movement of the prostate gland by 0.5 cm or more in 31 of 50 consecutive patients. The range of motion was 0 to 2 cm with an average of 0.5 cm (1.0 cm in the 31 patients). Six additional patients (five with local recurrence following I-125 seed implantation) were analyzed separately using CT scans. Registered CT images (3 mm slices) taken with the rectum and bladder full and/or empty provided direct evidence of prostate movement in 3 of the 6 patients. The dosimetric consequences of this movement are demonstrated using 3-dimensional dose distributions.

Concurrent chemotherapy and radiation therapy followed by transhiatal esophagectomy for local-regional cancer of the esophagus.

Forty-three patients with local-regional squamous-cell carcinoma of the esophagus or adenocarcinoma of the esophagus, cardia, or gastroesophageal junction were treated with concurrent cisplatin, vinblastine, fluorouracil (5-FU), and radiation therapy (RT) over 21 days. A transhiatal esophagectomy (THE) was planned on day 42. Seventy-nine percent had T2 primaries by clinical staging and 56% had enlarged regional nodes (N) on computed tomographic (CT) scan. Forty-one patients completed the preoperative treatment and went to surgery (95% operability rate), and 36 (84%) were completely resected. Ten of the 41 operative candidates had no evidence of tumor in the resected esophagus and nodal tissue (tumor0 node0; T0N0), 24% complete response (CR). Myelosuppression was the major toxicity with grade 3 or 4 leukopenia in 93% of patients and two preoperative treatment-related deaths. At a median follow-up of 26 months, the median survival time (MST) of all 43 patients registered on study has not been reached. The MST of the 36 completely resected patients and the 10 complete responders has not been reached; 70% and 100%, respectively, are alive at 24 months. The MST by histology is 21 months for the 22 squamous patients and has not been reached for the 21 adenocarcinoma patients registered on study. In a prognostic factor analysis, clinical N status, histology, and the percent of cisplatin and vinblastine tolerated were significant predictors for survival. These survival results suggest a significant improvement over the 14-month MST observed in our previous trial using preoperative chemotherapy only in a similar patient population, and a 12-month MST in a historic control group undergoing THE. A randomized trial is now in progress to convincingly determine if survival is prolonged by this therapy.

Boost treatment of the prostate using shaped, fixed fields

Using a CT-based, 3-D treatment planning system and Beams Eye-View (BEV) displays, shaped fixed-field techniques have been developed for external beam boost treatment of Stage C carcinoma of the prostate. The basic technique comprises three sets of opposing beams (laterals and +/- 45 degrees with respect to the lateral) into a 6-field arrangement. Target volumes together with bladder and rectal wall volumes are outlined on axial CT slices and combined to form 3-D volumes. For each field, an interactive BEV display is produced showing the target volume in its correct 3-D geometrical perspective and an auto-block routine is used to design focused blocks which conform to that volume. Full 3-D volume calculations computed for those plans on 17 patients were analyzed along with similar calculations for more traditional unblocked 4-field box and bilateral arc techniques. Compared to the 95% isodose volume for the 6-field conformational technique, traditional open beam full target coverage techniques typically produce high dose volumes which cover up to five times as much uninvolved tissue. Dose volume histograms illustrate that typically half as much bladder and rectal tissue is treated to high dose using the conformational boost techniques. From the dosimetric perspective of sparing normal tissues, shaped fixed-field boost techniques are shown to be clearly superior to traditional full coverage bilateral arc techniques. Smaller 8 cm X 8 cm arc techniques are shown to be quantitatively unacceptable for treatment of this advanced stage disease, as they typically misses 20-35% of the target volume.

Chemotherapy and radiation therapy before transhiatal esophagectomy for esophageal carcinoma.

Recent efforts to improve survival in patients with esophageal carcinoma have combined both systemic and local therapy. From October 1985 to October 1987, 43 patients with local-regional esophageal cancer (adenocarcinoma in 21, squamous cell in 22) were treated with cisplatin, vinblastine, and 5-fluorouracil chemotherapy concurrent with 4,500 cGy radiation therapy for 21 days before transhiatal esophagectomy 3 weeks later. Two patients died of chemotherapy/radiation therapy toxicity. Forty-one completed preoperative chemotherapy/radiation therapy. At operation, 2 patients had incurable metastatic disease; 39 underwent transhiatal esophagectomy. Eleven patients had no residual tumor in the resected specimen for a 27% (11 of 41) pathological complete response rate. Preoperative chemotherapy/radiation therapy resulted in no increased perioperative morbidity as compared with our historical controls. One patient died postoperatively of an unrecognized brain metastasis (2% operative morbidity). At a median follow-up of 27 months, 20 patients (47%) are alive and clinically disease-free and 21 have died, 19 from progression of their carcinoma. The median survival time for all 43 patients is 29 months (Kaplan-Meier estimate), and cumulative survival is 72% at 12 months, 60% at 24 months, and 46% at 36 months. All 11 patients with a complete response are alive at a median follow-up of 36 months, and all are disease-free. The 2-year survival of 60% of this group as compared with 32% in our earlier patients treated with transhiatal esophagectomy alone suggests that intensive combined modality therapy improves survival in these patients. A randomized prospective trial is now in progress.

Concurrent preoperative chemotherapy and radiation therapy in localized esophageal adenocarcinoma

Twenty‐four patients with localized, potentially resectable adenocarcinoma of the esophagus were enrolled in this study to evaluate the use of preoperative chemotherapy and radiation therapy, followed by transhiatal esophagectomy. The patients were newly diagnosed and had received no prior treatment. Radiation therapy consisted of 4900 cGy, administered as 350‐cGy fractions 5 days a week for 14 fractions. The chemotherapy consisted of 5‐fluorouracil 300 mg/m2/day administered as a continuous 24‐hour intravenous infusion for 96 hours each week, concomitantly with the radiation therapy. After a 3‐week rest, patients underwent transhiatal esophagectomy. Twenty‐two patients could be observed for their responses to the chemotherapy and radiation regimen. Radiographically, 41% showed improvement, 36% had stable disease, and 23% had progression. Nineteen patients underwent surgery; all patients had total gross removal of disease, and two patients had a complete histologic response.

Brain metastasis in patients with superior sulcus tumors.

During a 20‐year period, from 1963 to 1983, 68 patients were treated for carcinoma of the lung presenting in the superior sulcus. Their ages ranged from 41 to 79 years (median, 56 years). Thirty‐six patients had squamous cell carcinoma, 13 had adenocarcinoma, 14 had large cell carcinoma, two had small cell carcinoma, and three had clinical diagnosis only. All tumors were considered to be inoperable or unresectable and were treated with external irradiation alone. The 3‐year disease‐free survival was 25%. Brain metastasis developed in 23 patients (34%); the brain was the first site of metastasis in 16 patients (24%), five of whom eventually developed other sites of metastasis. The cumulative probability of brain metastasis was 53% at 3 years. Brain metastases were seen in ten patients (28%) with squamous cell carcinoma, five patients (38%) with adenocarcinoma, seven patients (50%) with large cell carcinoma, and one patient without a histocytologic diagnosis. The proportion of patients younger than 60 years (19/41, 46%) who developed brain metastasis was significantly greater than that for patients 60 years or older (4/27, 15%) (P ± 0.01). Nine of 11 patients with metastasis only to the brain died as a consequence of the intracranial disease 1 to 13 months (median, 6 months) after the diagnosis of brain metastases. The other two patients received therapeutic irradiation to the entire brain and survived longer than 5 days after the whole‐brain irradiation: one died at 62 months of intercurrent disease, and the other is alive and well 129 months after diagnosis. The high probability of brain metastasis from superior sulcus tumors, regardless of histopathologic type and the frequency with which the brain is the only site of clinical failure, suggest that systematic prophylactic cranial irradiation could reduce the morbidity and perhaps even contribute favorably to the survival of these patients.

The management of vaginal melanoma

Between 1964 and 1987 ten patients with vaginal melanoma were treated at the University of Michigan Hospital. Five of the six patients who underwent radical surgery had adequate information concerning the first site of relapse, and in four of these five, pelvic sites or locoregional lymph nodes were the first sites of recurrent disease. One of these patients developed a 17‐cm pelvic recurrence, which responded with a 75% reduction in size 3 months after completion of radiotherapy given in high individual fractions (400 cGy × 11). Three patients were managed with local resection, and all developed recurrent locoregional disease. One patient presented with metastatic disease. We conclude that locoregional control of vaginal melanoma is difficult to achieve with surgery alone. We hypothesize that preoperative radiotherapy to the pelvis (500 cGy × 6 given 3 days a week to the whole pelvis with subsequent consideration for a vaginal boost field) may improve the poor rate of locoregional control of vaginal melanoma that is seen when surgery alone is used.

Optimal coverage of peritoneal surface in whole abdominal radiation for ovarian neoplasms

Patterns of failure in ovarian carcinoma include early seeding of the entire peritoneal cavity. Inability to encompass the anatomic extent of the peritoneal cavity is a possible factor leading to relapse. However, little has been published regarding technical advances in optimal coverage of the peritoneal surface in whole abdominal radiation. In the Department of Radiation Oncology at the University of Michigan, 21 consecutive patients were analyzed prospectively in regard to adequate coverage of peritoneum in the treatment of advanced ovarian carcinoma. Simulation and focused blocks were designed to treat the whole abdomen. CT treatment planning studies were obtained with the entire peritoneum identified as the target volume. Simulator designed blocks were projected over the CT scans throughout the treatment volume. Dose volume histograms were used to calculate the amount of target volume missed for each treatment plan. All treatment plans demonstrated different degrees of volume miss, ranging from 1 cm3 to 837.3 cm3 with a median of 137.9 cm3 overall. Volume missed directly correlated with increasing patient weight and flatter pelvic shape, but poorly with AP separation. This was especially evident for patients requiring treatment at extended distances in both the supine and prone positions. We conclude that bony landmarks are poor guidelines in designing pelvic blocks, especially in heavy patients and patients requiring treatment in both prone and supine positions. CT treatment planning is helpful to ensure optimal peritoneal coverage.

Treatment of T3a bladder cancer with iridium implantation

A total of 7 patients with high grade, T3a (Stage B2) bladder cancer were treated with external radiation therapy and interstitial iridium implantation from May 1986 through March 1988. Follow-up has ranged from nineteen to sixty-one months with a median of forty months. One patient has required a cystectomy and is currently free of disease, and 1 patient has had recurrence of his cancer and metastatic carcinoma has developed; 5 are free of disease and have maintained their usual state of bladder function. Iridium implantation maintains bladder function and is effective therapy for selected individuals with localized, muscle-invading bladder cancer.