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Biomedical subjects

B D Minsky

Publications and source records attributed to B D Minsky.

At least 37 records · Page 2Linked to original sources

Postoperative radiation therapy for rectal cancer combined with UFT/leucovorin.

Postoperative combined-modality therapy with fluorouracil (5-FU) and radiation therapy is accepted practice for high-risk rectal cancer. Postoperative pelvic radiotherapy alone may improve pelvic control, but is not associated with an improvement in survival. Protracted infusional 5-FU has been associated with decreased tumor recurrence and improved survival when combined with postoperative adjuvant pelvic radiotherapy. The use of new drugs and alternative ways of administering 5-FU is desirable. UFT plus leucovorin is an oral 5-FU prodrug with efficacy equal to 5-FU plus leucovorin in metastatic colorectal cancer. A combination of postoperative adjuvant UFT plus leucovorin concurrent with radiation therapy should be feasible, and the design of an ongoing phase I trial is presented.

Administration, Oral↗

Conservative management of rectal cancer with local excision and postoperative adjuvant therapy.

BACKGROUND: To determine the local control, survival, and functional outcome of local excision plus postoperative therapy for patients with rectal cancer. METHODS: A total of 39 patients underwent a local excision (2 with snare excision of a T1 polyp and 37 with full-thickness local excision) followed by postoperative radiation therapy +/- 5-FU-based chemotherapy. The median follow-up was 41 months, and 11 patients had positive margins. RESULTS: The 5-year actuarial colostomy-free survival was 87% and overall survival was 70%. Crude local failure increased with T stage: 0% T1, 24% T2, and 25% T3. Of the 8 patients (21%) who developed local failure, 5 underwent salvage APR and were locally controlled. Actuarial local failure at 5 years was 31% for T2 disease and 27% for the total patient group. In the 32 patients with an intact sphincter, 94% had good to excellent sphincter function. CONCLUSION: Although local failure in patients with T2 tumors has increased since our prior report, the survival, sphincter function, and local salvage rates are acceptable. Local excision and postoperative therapy remains a reasonable alternative to APR in selected patients.

Adenocarcinoma↗

The evaluation and treatment of patients receiving radiation therapy for carcinoma of the esophagus: results of the 1992-1994 Patterns of Care Study.

BACKGROUND: For the first time, a Patterns of Care Study (PCS) was conducted in 1992-1994 to determine the national practice standards in evaluating and treating patients with esophageal carcinoma and to determine the degree to which clinical trials have been incorporated into national practice. METHODS: A national survey of 61 institutions using 2-stage cluster sampling was conducted, and specific information was collected on 400 patients with squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who received radiation therapy (RT) as part of definitive or adjuvant management of their disease. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Chi-square tests for significant differences between academic and nonacademic institutions for a particular variable were performed. RESULTS: The median age of patients was 66.7 years (range, 26-89 years); 76.5% were male and 23.5% were female. Karnofsky performance status was > or = 80 for 88.3% of patients. Squamous cell carcinoma was diagnosed in 61.5% and adenocarcinoma in 36.8%. Fifteen percent were Clinical Stage (CS) I, 39.5% CS II, and 29.5% CS III. Evaluative procedures included endoscopy (>93%), computed tomography (CT) of the chest (86%), CT of the abdomen (75%), esophagography (68.5%), and endoscopic ultrasound (3.5%). Endoscopic ultrasound and CT of the chest were performed significantly more frequently at academic than nonacademic facilities (6.1% vs. 1.0% and 91.9% vs. 81.3%, respectively). Three-quarters of all patients received chemotherapy and RT and 62.5% received concurrent chemotherapy and RT as part of their treatment. Treatments included chemotherapy plus RT (54.0%), RT alone (20.3%), preoperative chemotherapy + RT (13.3%), postoperative chemotherapy + RT (7.7%), postoperative RT (3.5%), and preoperative RT (1.2%). The chemotherapeutic agents most frequently used were 5-fluorouracil (84%), cisplatin (64%), and mitomycin (9%); academic instututions used cisplatin significantly more often and mitomycin significantly less often than nonacademic institutions. Brachytherapy was used in 8.5% of cases. The median total dose of external beam radiation was 50.4 gray and the median dose per fraction was 1.8 gray. CONCLUSIONS: This study establishes the national benchmarks for the evaluation and treatment of patients with esophageal carcinoma at radiation facilities in the U.S. It also indicates that the majority of patients given RT as a component of treatment for esophageal carcinoma receive chemoradiation rather than RT alone, as supported by clinical trials. Although some differences in the evaluation of esophageal carcinoma were noted between academic and nonacademic facilities, there was no difference in the frequency of use of chemoradiation versus RT by facility type.

Adenocarcinoma↗

Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus.

PURPOSE: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. METHODS AND MATERIALS: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m2/24 h x 5 days) and cisplatin (100 mg/m2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m2/24 h x 5 days) and cisplatin (75 mg/m2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. RESULTS: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. CONCLUSION: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123.

Adult↗

30 Gy may be an adequate dose in patients with anal cancer treated with excisional biopsy followed by combined-modality therapy.

BACKGROUND AND OBJECTIVES: There are a subset of patients with invasive anal cancers who undergo an excisional biopsy either before or after combined-modality therapy (CMT). The objective of this study is to determine whether these patients can be adequately treated with a lower dose of pelvic radiation therapy. METHODS: A total of 25 patients were treated with CMT either before or after an excisional biopsy. The four subsets included 8 patients with initial excision followed by CMT with 30-34 Gy (EX/30), 6 patients with initial excision followed by CMT with 45-50.4 Gy (EX/45), 10 patients treated by CMT with 30 Gy followed by an excision (30/EX), and 1 patient by CMT with 45 Gy followed by an excision (45/EX). RESULTS: For the total group, the actuarial 5-year disease-free survival was 78%, overall survival was 86%, colostomy-free survival was 91%, and local control was 82%. When patients received CMT either before or following an excision, the actuarial local control and survival results with 30-34 Gy vs. 45-50.4 Gy were similar. In contrast to radiation dose, in patients who received 30-34 Gy, the sequence of the excision (before or after CMT) did appear to have a borderline significant impact on local control. Actuarial 5-year local control was 100% for EX/30 vs. 67% for 30/EX (P = 0.08). CONCLUSIONS: Because of the small number of patients in each group and the retrospective nature of the analysis, it is difficult to draw definitive conclusions from this study. However, our data suggest that in patients who are selected to undergo an initial excisional biopsy followed by CMT, 30 Gy may be an adequate radiation dose. Local control may be higher in patients who undergo an excisional biopsy followed by CMT compared with the converse.

Adenocarcinoma↗

Esophageal cancer phospholipids correlated with histopathologic findings: a 31P NMR study.

We analyzed 36 esophageal tumor specimens for phospholipid content using phosphorus nuclear magnetic resonance spectroscopy (31P NMR) and correlated the individual phospholipid profiles with specific clinical and histopathologic features. Among the 18 phospholipids identified in the esophageal tumor specimens, the mean mole percentage concentration of dimethylphosphatidylethanolamine, lysoalkylacylphosphatidylcholine, lysophosphatidic acid, lysophosphatidylcholine (deacylated at the glycerol-1 carbon), and lysoethanolamine plasmalogen correlated with pathologic T stage, nuclear grade, or the presence of lymphatic invasion. 31P NMR produces well-dispersed phospholipid spectra and a precise determination of phospholipid relative mole percentages. These data provide a statistical correlation between histopathologic features and molecules known to play an important role in cellular activities and processes unique to malignant tissues.

Esophageal Neoplasms↗

Sphincter preservation of leiomyosarcoma of the rectum and anus with local excision and brachytherapy.

PURPOSE: The aim of this study was to determine the outcome of patients with leiomyosarcoma of the rectum or anus treated with local excision and brachytherapy. METHODS: Eight patients with leiomyosarcoma of the rectum (7 patients) or anus (1 patient) were treated with a transanal excision followed by a temporary iridium-192 interstitial implant to 4,500 cGy. Median tumor size was 4.2 (range, 1.5-5) cm. Margins were positive in six patients, negative in one patient, and close in one patient. RESULTS: With a median follow-up of 53 months, median survival time was 53 months and the three-year actuarial survival rate was 71 percent. The cumulative incidence of failure as a component of failure for local was 25 percent (2/8), for abdominal was 0 percent (0/8), and for distant was 25 percent (2/8). Four patients eligible for functional analysis all had excellent sphincter function (1-2 bowel movements per day, no soilage). CONCLUSION: In selected patients the use of conservative surgery followed by brachytherapy is a reasonable alternative to an abdominoperineal resection. However, more experience and longer follow-up are needed before this approach can be recommended routinely.

Anal Canal↗

All patients with small intramural rectal cancers are at risk for lymph node metastasis.

PURPOSE: Although local excision can be curative in patients with early-stage rectal cancer, approximately 20 percent of patients will develop local recurrence, many as a result of unrecognized and unresected regional lymph node metastases. Our objective was to determine if standard pathologic factors can predict lymph node metastases in small intramural rectal cancers and provide a basis for patient selection for nonradical surgery. METHODS: Between June 1986 and September 1996, 318 patients with T1 or T2 rectal cancers underwent radical resection at our institution. Of these, 159 patients (48 T1 and 111 T2) were potentially eligible for curative local excision (< or =4 cm in size, < or =10 cm from the anal verge, no synchronous metastases), and the prevalence of lymph node metastases based on T stage and other pathologic factors was analyzed in this group. RESULTS: The overall frequency of lymph node metastasis was 15 percent (24/159 patients). T stage (T1, 10 percent; T2, 17 percent), differentiation (well-differentiated or moderately differentiated, 14 percent and poorly differentiated, 30 percent), and lymphatic vessel invasion (lymphatic vessel invasion-negative, 14 percent and lymphatic vessel invasion-positive, 33 percent) influenced the risk of lymph node metastasis. However, only blood vessel invasion (blood vessel invasion-negative, 13 percent and blood vessel invasion-positive, 33 percent) reached statistical significance as a single predictive factor (P=0.04). Tumors with no adverse pathologic features (low-risk group) had a lower overall frequency of lymph node metastasis (11 percent) compared with the remaining tumors (high-risk group, 31 percent; P=0.008). However, even in the most favorable group (T1 cancers with no adverse pathologic features) lymph node metastases were present in 7 percent of patients. CONCLUSION: In rectal cancer patients potentially eligible for local excision, the overall risk of undetected and untreated lymph node metastases is considerable (15 percent). The use of pathologic factors alone after local excision does not reliably assure the absence of lymph node metastases.

Adenocarcinoma↗

Surgical salvage of recurrent rectal carcinoma after curative resection: a 10-year experience.

BACKGROUND: Local recurrence after resection of rectal carcinoma is a difficult clinical problem that adversely affects both survival and quality of life. Surgical resection is possible for a subset of patients with localized recurrences. We reviewed our experience with surgical salvage of recurrent rectal carcinoma, to determine predictors of resectability and postsalvage survival rates. METHODS: A 10-year, retrospective analysis of 131 patients who underwent exploration with curative intent for local recurrence after radical resection of rectal carcinomas, in a single referral institution, was performed. Preoperative and pathological factors were examined for their ability to predict postresection survival rates and resectability. RESULTS: The overall 5-year survival rate for patients who underwent exploration with curative intent was 24%. Resection of recurrent disease was possible for 103 of 131 (79%) patients, with a resulting 5-year survival rate of 31%. Patients who were treated initially with abdomino-perineal resection (n = 35) presented later and were less likely to have resectable tumors than were those treated initially with some form of sphincter-preserving resection (n = 96). Among patients who could undergo resection, normal carcinoembryonic antigen levels and recurrent disease limited to the bowel wall were both favorable features. CONCLUSIONS: Surgical salvage of local recurrence after radical resection of rectal carcinoma can be performed safely and can result in substantial long-term survival benefits for selected patients.

Combined Modality Therapy↗

Recommended colorectal cancer surveillance guidelines by the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based, postoperative surveillance strategy for the detection of recurrent colon and rectal cancer. Tests are to be recommended only if they have an impact on the outcomes listed below. POTENTIAL INTERVENTION: All tests described in the literature for postoperative monitoring were considered. In addition, the data were critically evaluated to determine the optimal frequency of monitoring. OUTCOMES: Outcomes of interest included overall and disease-free survival, quality of life, toxicity reduction, and cost-effectiveness. The American Society of Clinical Oncology (ASCO) Colorectal Cancer Surveillance Expert Panel was guided by the principle of cost minimization, ie, when two strategies were believed to be equally effective, the least expensive test was recommended. EVIDENCE: A complete MEDLINE search was performed of the past 20 years of the medical literature. Keywords included colorectal cancer, follow-up, and carcinoembryonic antigen, as well as the names of the specific tests. The search was broadened by articles from the tumor marker ASCO panel literature search, as well as from bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COSTS: The possible consequences of false-positive and false-negative tests were considered in evaluating a preference for one of two tests that provide similar information. Cost alone was not a determining factor. RECOMMENDATIONS: The expert panel's recommended postoperative monitoring schema is discussed in this article. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board of Directors examined this document. SPONSOR: American Society of Clinical Oncology.

Colorectal Neoplasms↗

Adjuvant postoperative combined-modality therapy for rectal cancer.

A number of advances have been made in the use of adjuvant chemotherapy for resectable rectal cancer. Whereas pelvic radiation therapy has been shown to increase local control in patients with clinically resectable disease, systemic chemotherapy is needed in addition to further improve local control and overall survival. In this review, the experience treating patients with clinically resectable rectal cancer in the postoperative adjuvant setting will be examined. Data from ongoing and recently completed randomized trials as well as the design of innovative phase I/II programs will be discussed.

Aged↗

Carcinoma of the esophagus. Part 1: Primary therapy.

The two general treatment approaches for esophageal cancer include primary treatment (surgical or nonsurgical) or adjuvant treatment (preoperative or postoperative). Due to differences in the patient populations selected for surgical or nonsurgical therapies, which may bias the results against nonsurgical therapy, it is difficult to determine the best treatment approach for this disease. The standard of care is either surgery alone or primary combined-modality therapy. Based on a nonrandomized comparison of the data from recent intergroup trials, the results of these two approaches are similar. For patients treated without surgery, the intergroup INT 0123 trial will determine whether higher doses of radiation are of benefit. No clear survival advantage has been seen with preoperative or postoperative adjuvant radiation therapy alone or chemotherapy alone. The randomized trials comparing preoperative combined-modality therapy vs surgery alone reveal encouraging results for the combination approach but need further confirmation. For patients treated with combined-modality therapy, the ideal regimen remains to be determined. The first part of this two-part article focuses on the rationale for and results of primary therapy for esophageal carcinoma. Part 2, which will appear in next month's issue, covers adjunctive therapy.

Adenocarcinoma↗

Adjuvant therapy of rectal cancer.

For patients with clinically resectable stage T3 and/or node-positive rectal cancer, adjuvant radiation therapy decreases the rate of local recurrence. The addition of systemic chemotherapy further enhances local control and improves survival. Compared with postoperative therapy, preoperative treatment may have less toxicity and may increase the chance of sphincter preservation. The acute and long-term toxicity of pelvic radiation is related to the technique of delivery. Therefore, appropriate conventional radiation doses and techniques are recommended. Randomized trials comparing preoperative and postoperative combined modality therapy are in progress.

Antineoplastic Agents↗

Carcinoma of the esophagus. Part 2: Adjuvant therapy.

The two general treatment approaches for esophageal cancer are primary treatment (surgical or nonsurgical) or adjuvant treatment (preoperative or postoperative). Due to differences in the patient populations selected for surgical or nonsurgical therapies, which may bias the results against nonsurgical therapy, it is difficult to determine the best treatment approach for this disease. The standard of care is either surgery alone or primary combined-modality therapy. Based on a nonrandomized comparison of the data from recent intergroup trials, the results of these two approaches are similar. For patients treated without surgery, the intergroup INT 0123 trial will determine whether higher doses of radiation are of benefit. No clear survival advantage has been seen with preoperative or postoperative adjuvant radiation therapy alone or chemotherapy alone. The randomized trials comparing preoperative combined-modality therapy vs surgery alone reveal encouraging results for the combination approach but need further confirmation. For patients treated with combined-modality therapy, the ideal regimen remains to be determined. Part 1 of this two-part review, which appeared in last month's issue, centered on primary therapy for esophageal carcinoma. This part explores the rationale for and results of adjuvant therapy.

Carcinoma↗

Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.

BACKGROUND: We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS: Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.

Adenocarcinoma↗

High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer.

PURPOSE: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo). RESULTS: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery. CONCLUSION: HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.

Adenocarcinoma↗