Biomedical subjects

B D Minsky

Publications and source records attributed to B D Minsky.

At least 73 records · Page 4Linked to original sources

PubMed1996

Radiation therapy alone or combined with chemotherapy in the treatment of esophageal cancer.

Radiation therapy has been used in the adjuvant setting or as a primary treatment modality for esophageal cancer. Although there are design flaws in all of the trials of adjuvant radiation therapy for esophageal cancer, there is no clear survival advantage when radiation therapy is delivered in the adjuvant setting (preoperatively or postoperatively). Phase II results of preoperative, combined modality therapy are encouraging; however, the approach remains investigational. When radiation therapy is used as a primary modality, the most favorable results are seen when it is combined with adequate doses of systemic chemotherapy. Phase III intergroup trials are in progress which are examining the effectiveness of higher doses of radiation therapy when combined with chemotherapy.

Brachytherapy↗

PubMed1996

Neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus: a preliminary analysis of the phase II intergroup trial 0122.

PURPOSE: To determine the preliminary acute toxicity and survival results of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. MATERIALS AND METHODS: Forty-five patients with clinical stage T1-4N0-1M0 squamous cell carcinoma were entered onto the trial. Eight patients were declared ineligible after registration. Patients received three monthly cycles of fluorouracil (5-FU; 1,000 mg/m2/24hr for 5 days) and cisplatin (100 mg/m2 on day 1) (neoadjuvant segment) followed by two additional monthly cycles of 5-FU (1,000 mg/m2/24hr for 5 days) and cisplatin (75 mg/m2 on day 1) plus concurrent 64.8 Gy (combined modality segment). RESULTS: With a median follow-up of 15 months in surviving patients, the incidence of total grade 3+ toxicity during the neoadjuvant chemotherapy segment was 61%, and during the combined modality segment was 72%. Of the 33 patients who started radiation therapy, 91% were able to complete the full course. There were six deaths during treatment, five of which (11%), because of nadir sepsis and/or dehydration, were treatment-related. For the 37 eligible patients, the median disease-free survival duration was 9 months, and the overall median survival was 20 months. CONCLUSION: The preliminary analysis of this trial demonstrated that the incidence of grade 3+ toxicity was similar to that reported in the combined modality arm of the prior Radiation Therapy Oncology Group (RTOG) intergroup esophageal trial RTOG 85-01. However, because of the increased incidence of treatment-related mortality, this treatment program will not be used as an experimental arm of intergroup trial INT 0123 (RTOG 94-05).

Adult↗

PubMed1996

Male and female sexual and urinary function after total mesorectal excision with autonomic nerve preservation for carcinoma of the rectum.

BACKGROUND: We performed a study to assess sexual and urinary function after total mesorectal excision with autonomic nerve preservation for primary carcinoma of the rectum. STUDY DESIGN: We studied retrospectively postoperative sexual and urinary function in 136 (78 percent) of 175 eligible patients (82 males and 54 females) who responded to a standardized questionnaire. RESULTS: The ability to engage in intercourse was maintained by 86 percent of the patients younger than 60 years of age, and by 67 percent of patients 60 years and older. Eighty-seven percent of male patients maintained their ability to achieve orgasm. The type of surgery (abdominoperineal resection compared to low anterior resection), and age equal to or greater than 60 years were significantly associated with male sexual dysfunction. Of the female patients, 85 percent were able to experience arousal with vaginal lubrication and 91 percent could achieve orgasm. The majority of patients had few or no complaints related to urinary function. Serious urinary dysfunction such as neurogenic bladder was not encountered. CONCLUSIONS: Autonomic nerve preservation in association with total mesorectal excision reduces the operative morbidity rate and is successful in minimizing sexual and urinary dysfunction in the operative treatment of patients with carcinoma of the rectum.

Adult↗

PubMed1996

The role of radiation therapy in gastric cancer.

Radiation therapy has been used as an adjuvant, primary, and palliative treatment modality for gastric cancer. In the adjuvant setting, the role of postoperative radiation therapy plus chemotherapy is being examined in the phase III Intergroup trial 0116. Until the results of this trial are available, the standard treatment after a complete resection (with or without positive locoregional lymph nodes) is observation alone. In patients who are selected to receive adjuvant therapy, locoregional radiation to 45 Gy plus 5-fluorouracil (5-FU)-based chemotherapy is recommended. In patients with locally unresectable or residual disease, postoperative radiation therapy and 5-FU-based chemotherapy may decrease locoregional failure and improve survival. Intraoperative radiation therapy appears promising; however, it remains investigational. In the palliative setting, radiation therapy offers symptomatic relief in the majority of patients.

Chemotherapy, Adjuvant↗

PubMed1996

Multidisciplinary management of resectable rectal cancer.

The standard adjuvant therapy for resectable T3 and/or N1-2 rectal cancer is pelvic radiation therapy plus fluorouracil (5-FU)-based chemotherapy. Two randomized intergroup trials, INT 0114 and INT 0144, will help determine the ideal chemotherapeutic agents and their routes of administration in the postoperative setting. The randomized National Surgical Adjuvant Project for Breast and Bowel Cancers trial NSABP R-03 and the INT 0147 trial will compare the efficacy and functional results of the preoperative and postoperative combined-modality therapy approaches. The delivery of effective therapies, as well as the development of more innovative approaches, is enhanced by a multidisciplinary collaboration among medical, surgical, and radiation oncologists.

Chemotherapy, Adjuvant↗

PubMed1995

Characterization of malignant colon tumors with 31P nuclear magnetic resonance phospholipid and phosphatic metabolite profiles.

BACKGROUND: To further characterize selected pathologic features on a biochemical level, the authors analyzed the nuclear magnetic resonance metabolite and phospholipid spectra of 30 malignant colon tumors using 31P magnetic resonance spectroscopy. METHODS: Eleven individual generic phospholipids were identified in the spectra of 17 phospholipid extracts, and 31 individual phosphatic metabolites were identified in the spectra of 13 perchloric acid extracts. The metabolites and lipids were quantified for statistical intergroup comparisons based on tumor stage, lymph node status, differentiation, mucin production, blood vessel invasion (BVI), and lymphatic vessel invasion (LVI). RESULTS: Significant elevations in the relative concentration of alpha-glycerol phosphate were noted when comparing AJCC tumor classification (T3 vs. T2, 0.92 +/- 0.14 vs. 0.46 +/- 0.11, P < 0.009), tumor differentiation (moderately vs. well differentiated, 0.92 +/- 0.14 vs. 0.46 +/- 0.11, P < 0.009), and BVI (presence vs. absence, 1.03 +/- 0.04 vs. 0.68 +/- 0.10, P < 0.028) by elastic tissue stain. Among the tissue phospholipids analyzed, the relative concentration of a choline phospholipid was significantly different when comparing moderately and poorly differentiated tumors (6.26 +/- 0.56 vs. 3.29 +/- 0.30, P < 0.001), T2 and T3 tumors (3.90 +/- 0.45 vs. 6.31 +/- 0.56, P < 0.009), and mucin-positive vs. mucin-negative tumors (4.46 +/- 0.56 vs. 6.83 +/- 0.76, P < 0.028). Differences in lymph node status of the cases analyzed in this study (lymph node positive vs. lymph node negative) were noted for tumors with elevated levels of sphingomyelin (8.13 +/- 0.40 vs. 6.88 +/- 0.16, P < 0.02), diminished levels of phosphatidylinositol (5.25 +/- 0.27 vs. 6.38 +/- 0.34, P < 0.02), elevated levels of beta-glycerol phosphate (5.30 +/- 0.70 vs. 1.20 +/- 0.06, P < 0.05), and elevated levels of glycerol 3-phosphoserine (0.48 +/- 0.01 vs. 0.23 +/- 0.02, P < 0.002). CONCLUSIONS: The characteristic differences in the phospholipid and intermediate phosphate metabolite profiles identified through magnetic resonance spectroscopic and histopathologic analysis may provide important information regarding the nature of tumor and cell membrane metabolism. Differences in these profiles may identify markers useful for biologic behavior, provide prognostic information, and characterize the impact of the pathologic features of colon cancer.

Cell Differentiation↗

PubMed1995

Sphincter preservation with preoperative radiation therapy and coloanal anastomosis.

PURPOSE: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. METHODS AND MATERIALS: Thirty patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (2: T2 28:T3) involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (range: 1.5-6 cm) and the median distance from the anal verge was 4 cm (range: 3-7 cm). The whole pelvis received 46.8 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 43 months (range: 6-82 months). RESULTS: Of the 29 patients who underwent resection, 3 (10%) had a complete pathologic response and 24 (83%) were able to successfully undergo a low anterior resection/colonanal anastomosis. The incidence of local failure was crude: 17% and 4-year actuarial: 23%. The 4-year actuarial survival was 75%. One patient developed a partial disruption of the anastomosis and two developed rectal stenosis. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in 22 of the 24 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 77%. The median number of bowel movements/day was two (range: 1-6). CONCLUSIONS: This technique may be an alternative to an abdominoperineal resection in selected patients. Continued follow-up is needed to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection.

Adenocarcinoma↗

PubMed1995

Sucrase-isomaltase is an independent prognostic marker for colorectal carcinoma.

PURPOSE: Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC). METHODS: SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months. RESULTS: Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold. DISCUSSION: These results indicate that SI is a prognostic marker for CRC that is independent of stage-related variables in patients who have undergone potentially curative resections.

Aged↗

PubMed1995

Adjuvant radiation therapy for colon cancer.

Post-operative radiation therapy has been used in selected patients with colon cancer. In contrast with rectal cancer, the primary failure pattern in colon cancer is abdominal. Local failure does occur, but is less frequent and more difficult to detect. Retrospective data suggest a benefit from local/regional radiation therapy on local control and disease-free survival in subsets of patients compared to historical controls. An ongoing phase III intergroup trial (INT 0130) will determine if local/regional radiation therapy improves the results of chemotherapy in subsets of patients with high-risk colon cancer. In general, the results of whole abdominal radiation plus 5-fluorouracil (5-FU) have been disappointing. However, the more recent data from the Southwest Oncology Group pilot trial are encouraging. In contrast to rectal cancer, where adjuvant chemotherapy plus radiation therapy is standard treatment in high-risk patients, the use of radiation therapy (either local/regional or whole abdomen) in colon cancer remains investigational.

Antimetabolites, Antineoplastic↗

PubMed1995

Relationship of acute gastrointestinal toxicity and the volume of irradiated small bowel in patients receiving combined modality therapy for rectal cancer.

PURPOSE: To determine the relationship between acute gastrointestinal (GI) toxicity during the combined modality segment and the volume of small bowel in the pelvic radiation field in patients who receive either preoperative or postoperative therapy for rectal cancer. PATIENTS AND METHODS: The patient population was derived from four consecutive phase I dose-escalation trials. Combined modality therapy included fluorouracil (5-FU), leucovorin ([LV] bolus daily x 5, days 1 and 29), and pelvic radiation. RESULTS: Twenty patients who received postoperative therapy had a larger volume of small bowel in the pelvic radiation field as compared with 60 who received preoperative therapy (462 +/- 129 v 212 +/- 44 cm3, P = .002). The most significant relationship between acute GI toxicity and volume of small bowel was seen in 12 patients who were treated on the preoperative sequential low-dose LV trial, all of whom received the maximum-tolerated dose (MTD) of 5-FU. The volume of small bowel in patients who experienced grade 3+ toxicity was 731 +/- 274 cm3, as compared with 145 +/- 58 in those who experienced grade 0 to 2 toxicity (P = .005). Likewise, logistic regression analysis showed that 26 patients who received the MTD of 5-FU had the most significant association between GI toxicity and volume of small bowel (P = .036). CONCLUSION: Our data suggest that the volume of small bowel in the pelvic radiation field may be dose-limiting in the delivery of high-dose 5-FU when combined with LV and radiation therapy.

Adenocarcinoma↗

PubMed1995

Efficacy of postoperative 5-FU, high-dose leucovorin, and sequential radiation therapy for clinically resectable rectal cancer.

We report the local control and survival in a previously reported phase I dose escalation trial of combined postoperative 5-FU, high dose leucovorin (LV), and sequential radiation therapy followed by maintenance LV/5-FU for the treatment of patients with clinically resectable rectal cancer. Following surgery for stages T3-4N0-2M0 primary (21) or recurrent (4) rectal cancer, 25 patients received 5-FU/LV x 1 cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of 5-FU/LV was given concurrent with the fourth week of radiation. Patients received an additional 10 cycles of LV/5-FU. The median follow-up was 40 months (range 18-52). The incidence of grade 3+ acute toxicity in the 9 patients who received the recommended dose of 5-FU was 44%. The local failure rate was 28%. Abdominal and distant failure rates were 24%. The 3-year actuarial disease-free survival was 74% and the overall survival was 80%. Our preliminary data reveal reasonable local control and survival rates. However, further follow-up is needed to assess our results at 5 years. Postoperative combined modality therapy with high-dose LV may be an option for the adjuvant treatment of patients with resectable rectal cancer.

Adenocarcinoma↗

PubMed1994

31P NMR phospholipid characterization of intracranial tumors.

Phospholipid extracts from 48 intracranial tumors were analyzed using 31P NMR. Phospholipids commonly identified in the tumor spectra included phosphatidylglycerol (PG), phosphatidic acid (PA), diphosphatidylglycerol (DPG), uncharacterized phospholipid (U), ethanolamine plasmalogen (EPLAS), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SM), lysophosphatidylcholine (LPC), phosphatidylinositol (PI), a choline phospholipid (CPLIP), and phosphatidylcholine (PC). Differences in the mean relative mole-percentage of phosphorus concentrations of individual phospholipids were used to differentiate among tumors. Neural sheath tumors (neurilemmoma, neurofibroma and fibrosarcoma) were noted to contain significantly elevated levels of SM relative to tumors of neural glial origin and individually, glioblastoma multiforme was noted to contain depressed levels of SM relative to neurilemmoma, neurofibroma and meningioma. Significantly decreased levels of PA were noted for glioblastoma relative to neurilemmoma along with significantly decreased levels of PE relative to meningioma. Elevated levels of LPC and CPLIP were seen in glioblastoma multiforme relative to meningioma. Additional findings included elevated levels of PC for glioblastoma multiforme relative to neurofibroma, and neurilemmoma was differentiated from neurofibroma with elevated levels of PA and depressed levels of PI. 31P NMR phospholipid analysis provides supplemental biochemical information which may be used to improve the interpretation of spectra acquired in vivo, and reveals important tumor-specific biochemical information which may further improve the understanding of the biological behavior of intracranial tumors.

Brain Chemistry↗

PubMed1994

Meningioma phospholipid profiles measured by 31P nuclear magnetic resonance spectroscopy.

Fourteen cases of intracranial meningioma were characterized after chloroform/methanol extraction by 31P nuclear magnetic resonance (NMR) spectroscopy at 202.4 MHz. Each phospholipid class detected in the extracts was identified and quantitated in terms of its molar percentage relative to the total phospholipids measured. The following phospholipids were assayed by 31P NMR: phosphatidylglycerol, phosphatidic acid, diphosphatidylglycerol, ethanolamine plasmalogen, phosphatidylethanolamine (PE), lysophosphatidylinositol, phosphatidylserine, sphingomyelin, lysophosphatidylcholine (LPC), phosphatidylinositol (PI), sphingosylphosphorylcholine and phosphatidylcholine. In addition, two unidentified phospholipids were detected with resonances at 0.13 and -0.78 ppm, respectively. Three distinct types of spectra were obtained on the extracts and grouped accordingly for comparison purposes. Type 1 tumors showed unusual 31P NMR profiles with low levels of PE and PI and elevated levels of LPC; type 2 tumors were characterized by low levels of the ethanolamine phospholipids and near equivalent levels of PI and LPC. The spectra of type 1 and type 2 tumors were characteristic of degenerative cells that lacked membrane permeability associated with loss of ethanolamine plasmalogen in the presence of significant phospholipid turnover. Meningiomas belonging to the third spectral type showed characteristics similar to those of normal tissues with normal levels of PE and ethanolamine plasmalogen, as well as very low levels of LPC relative to PI. Type 3 tumors lacked the characteristic signs of degeneration noted in type 1 and type 2 tumors. The data corroborate and augment in vivo spectroscopic findings reported earlier and demonstrate the value of 31P NMR spectroscopic phospholipid analysis on lipid extracts for the characterization of meningiomas.

Humans↗

PubMed1994

Long-term functional results of coloanal anastomosis for rectal cancer.

In a survey of patients treated with coloanal anastomosis for rectal cancer, 81 of 90 eligible patients responded to a questionnaire evaluating current anorectal function. Time from operation to assessment ranged from 1.3 to 12.3 years (median: 4.3 years). The median stool frequency was two per day; 22% of patients reported four or more stools per day. In the patients surveyed, fecal continence was complete in 51%, incontinence to gas only in 21%, minor leak in 23%, and significant leak in 5%. Complete evacuation of the neorectum was problematic in 32%. Overall function was excellent in 28%, good in 28%, fair in 32%, and poor in 12%. The impact of treatment variables on functional outcome was assessed by univariate and multivariate analyses. No surgical technique correlated with improved or impaired outcome. Time since surgery (reduced stool frequency) and use of postoperative adjuvant radiotherapy (increased stool frequency, increased difficulty with evacuation) did appear to influence functional outcome. We conclude that the functional results of coloanal anastomosis are good but not optimal. Continued investigation of the effects of surgical technique and adjuvant therapy is warranted.

Anal Canal↗

PubMed1994

Local excision and postoperative radiation therapy for rectal cancer.

PURPOSE: We report the results of 22 patients with localized, mobile, resectable rectal cancer treated with local excision and postoperative radiation therapy. METHODS AND MATERIALS: Margins were negative in 21 patients and unassessable in 1. The median follow-up was 37 months (range: 5-73 months). The median tumor size was 3.0 cm (range: 1-6.2 cm). Full-thickness local excisions were performed in 21 patients: transanal, 11; transsphincteric, 2; and posterior proctotomy (Kraske), 8. All margins were inked and were microscopically negative in 21. One patient had a transanal snare excision of a T1 polyp. Postoperatively patients received 4,500-4,950 cGy (median: 4,680 cGy) whole pelvis, and in 15 this was followed by a conedown to 360-1,000 cGy (median: 360 cGy). RESULTS: The 4-year actuarial survival was 79% and the 4-year actuarial colostomy-free survival was 73%. The incidence of local failure was 18% and increased with T stage: T1: 0/4 (0%); T2: 2/12 (17%); and T3: 2/6 (33%). Four patients developed local failure at 6, 10, 15, and 21 months. Of the four, three underwent salvage APR and were locally controlled at 6, 33, and 58 months following salvage surgery. The incidence of abdominal failure was 18% and distant failure was 18%. Of the 15 eligible patients, 14 (93%) had good or excellent sphincter function. CONCLUSIONS: The results of local excision and postoperative radiation therapy are encouraging; however, more experience is needed to determine if this approach ultimately has similar local control and survival rates as standard surgery.

Actuarial Analysis↗

PubMed1994

Preoperative combined modality treatment for rectal cancer.

The encouraging results achieved with adjuvant postoperative combined modality therapy in patients with resectable rectal cancer has prompted an increased interest in preoperative combined modality therapy. Based on the potential of such regimens to deliver higher chemotherapy doses, enhance downstaging, and decrease acute toxicity in patients with unresectable disease, this approach is attractive in patients with resectable rectal cancer. Randomized trials of preoperative vs postoperative combined modality therapy using combinations of bolus fluorouracil and leucovorin are in progress.

Combined Modality Therapy↗

PubMed1993

The efficacy of preoperative 5-fluorouracil, high-dose leucovorin, and sequential radiation therapy for unresectable rectal cancer.

BACKGROUND: The encouraging results seen in patients who received postoperative combined modality therapy in the adjuvant setting have prompted increased interest in preoperative combined modality therapy for patients with unresectable rectal cancer. The authors report the local control and survival of a previously reported Phase I dose escalation trial of combined preoperative 5-fluorouracil (5-FU), high-dose leucovorin (LV), and sequential radiation therapy followed by postoperative LV-5 FU for the treatment of patients with unresectable rectal cancer. METHODS: Twenty patients (13, primary and 7, recurrent disease) received LV-5-FU for one cycle. Radiation therapy (5040 cGy) began on day 8. A second cycle of LV-5-FU was given concurrently with week 4 of radiation. Six patients received intraoperative brachytherapy. Postoperatively, the patients received LV-5-FU. The pathologic complete response rate was 20%, and 89% underwent a complete resection with negative margins. RESULTS: The crude local failure rate was 26%, and the 3-year actuarial local failure rate was 29% (95% confidence interval [CI], +/- 8.94%). The crude abdominal and distant failure rates were 40% and 30%, respectively. The 3-year actuarial disease-free survival was 64% (95% CI, +/- 6.75%), and the overall survival was 69% (95% CI, +/- 7.65%). CONCLUSIONS: These preliminary data revealed encouraging local control and survival rates. Preoperative combined modality therapy is an attractive approach in patients with unresectable rectal cancer.

Aged↗

PubMed1993

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer.

PURPOSE: We performed a Phase I trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. METHODS AND MATERIALS: Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy, was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7-16 months). RESULTS: Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153,000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. CONCLUSIONS: Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, we do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate we remain encouraged with this approach.

Adult↗