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Biomedical subjects

M S Anscher

Publications and source records attributed to M S Anscher.

At least 19 recordsLinked to original sources
PubMed1995

Adjuvant radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate: ten-year update.

PURPOSE: To determine the role of adjuvant postoperative radiotherapy (RT) following radical prostatectomy (RP) in a group of patients with pathologic Stage T3/4 adenocarcinoma of the prostate followed for a median of 10 years after treatment. METHODS AND MATERIALS: Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have pathologic Stage T3/4. Forty-six received adjuvant RT and 113 did not. Radiotherapy usually consisted of 45-50 Gy to the whole pelvis followed by a boost to the prostate bed of 10-15 Gy, to a total dose of 55-65 Gy. Patients were analyzed with respect to survival, disease-free survival, local control, and freedom from distant metastases. A rising prostate-specific antigen in the absence of other evidence of relapse was scored as a separate category of recurrence. RESULTS: Both groups of patients have been followed for a median of 10 years. The actuarial survival at 10 and 15 years was 62% and 62% for the RT group compared to 52% and 37%, respectively, for the RP group (p = 0.18). The disease-free survival for the Rt group was 55% and 48% at 10 and 15 years, respectively, compared to 37% and 33% for the RP group (p = 0.16). Similarly, there was no difference in the rate of distant metastases between the two groups. In contrast, the local relapse rate was significantly reduced by the addition of postoperative radiotherapy. The actuarial local control rate at 10 and 15 years was 92% and 82%, respectively, for the RT group vs 60% and 53% for the RP group (p = 0.002). CONCLUSIONS: While postoperative pelvic RT significantly improves local control compared to RP alone for pathologic Stage T3/4 prostate cancer, it has no impact on distant metastases and consequently does not improve survival. These data are consistent with the conclusion that many patients with pathologic Stage T3/4 prostate cancer have occult metastases at presentation and will not be cured by local therapies alone. The optimal treatment for this patient population remains to be established.

Adult↗
PubMed1995

The efficacy of postprostatectomy radiotherapy in patients with an isolated elevation of serum prostate-specific antigen.

PURPOSE: To determine the efficacy of radiotherapy (RT) in patients with an isolated elevation of prostate specific antigen (PSA) after radical prostatectomy (RP). METHODS AND MATERIALS: Between November 1987 and May 1993, 53 patients with adenocarcinoma of the prostate were referred for pelvic RT for an elevated PSA after RP. No patient had clinically or radiographically apparent local or distant disease, nor had an undergone prior androgen ablation. Patients received a median dose of 61.2 Gy to the prostatic bed. An undetectable PSA was required to be considered disease free (NED). Univariate and multivariate analyses were performed to identify factors predictive of becoming disease free after RT. RESULTS: The median follow-up was 15 months. Of the 53 patients, 16 (30%) became NED after RT and 15 (28%) had a declining (n = 11) or stable (n = 4) PSA at last evaluation. The median time after RT to achieve an undetectable PSA was 9.3 months. At 12 and 24 months, the actuarial disease-free survival was 30 and 23%, respectively; actuarial progression-free survival was 71 and 26%, respectively. By univariate analysis, the last PSA level before RT (i.e., the pre-RT PSA) and an undetectable PSA after RP were significant predictors of becoming NED (p = 0.0001 and 0.04, respectively). However, on multivariate analysis, only the pre-RT PSA remained significant (p = 0.01). The mean pre-RT PSA differed significantly between patients who became NED after RT and those who did not (1.5 +/- 0.2 ng/ml vs. 7.6 +/- 1.6 ng/ml, respectively; p = 0.018). Fourteen of 27 (52%) patients with pre-RT PSA levels < or = 2.5 ng/ml became NED, vs. only 2 of 26 (8%) patients with higher levels. There were no severe acute or late sequelae of RT. CONCLUSION: Prostatic-bed RT for an elevated serum PSA after RP is most effective in patients with a pre-RT PSA < or = 2.5 ng/ml. Patients with significantly higher PSA values are unlikely to benefit from RT, possibly due to the presence of occult distant metastases. The optimal therapy for this latter group remains to be determined.

Aged↗
PubMed1995

Hepatic toxicity resulting from cancer treatment.

Radiation-induced liver disease (RILD), often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites approximately 2 weeks to 4 months after hepatic irradiation. There has been a renewed interest in hepatic irradiation because of two significant advances in cancer treatment: three dimensional radiation therapy treatment planning and bone marrow transplantation using total body irradiation. RILD resulting from liver radiation can usually be distinguished clinically from that resulting from the preparative regime associated with bone marrow transplantation. However, both syndromes demonstrate the same pathological lesion: veno-occlusive disease. Recent evidence suggests that elevated transforming growth factor beta levels may play a role in the development of veno-occlusive disease. Three dimensional treatment planning offers the potential to determine the radiation dose and volume dependence of RILD, permitting the safe delivery of high doses of radiation to parts of the liver. The chief therapy for RILD is diuretics, although some advocate steroids for severe cases. The characteristics of RILD permit the development of a grading system modeled after the NCI Acute Common Toxicity Criteria, which incorporates standard criteria of hepatic dysfunction.

Dose-Response Relationship, Radiation↗
PubMed1995

The effectiveness of immobilization during prostate irradiation.

PURPOSE: To evaluate the effect of a hemibody foam cradle on the reproducibility of patient setup during external beam radiation treatment of prostate cancer. METHODS AND MATERIALS: Between January 1992 and April 1993, 74 patients received external beam radiation treatment to the prostate +/- nodes, generally with a four-field box technique. Forty-four of the 74 patients had a custom-made hemibody foam cast used in an attempt to improve setup accuracy. A review of the routine weekly port films was performed following the completion of therapy to determine the reproducibility of patient setup in all 74 patients. The physician's request of an isocenter shift was used as an indicator of reproducibility. Neither the treating technologists nor the physicians knew at the time the films were taken that the port films would be reviewed for setup reproducibility at a later date. The results were compared between the patients treated with (44) and without (30) an immobilization device. RESULTS: In the 44 immobilized patients, 213 routine checks of the isocenter were performed during the 7-week course of radiation therapy. In 17.4% of these instances (37 out of 213), an isocenter shift was requested. This rate is compared to 23.1% (30 out of 130) in the 30 patients who did not have the immobilization device (p < 0.2). There was a statistically significant reduction in isocenter shifts requested in the anterior to posterior direction in the patients who were immobilized, 5.1% (9 out of 175) vs. 12.6% (13 out of 103) (p < 0.05, two tailed chi-square test). There was no significant improvement in the reproducibility of isocenter placement in the cephalad to caudal or right to left directions. CONCLUSIONS: This custom-made hemibody foam cradle appears to improve the reproducibility of patient setup during the 7-week course of fractionated external beam irradiation for patients with adenocarcinoma of the prostate. This type of immobilization device is now routinely used in our clinic and is recommended for all patients receiving pelvic radiotherapy. These devices are likely to be particularly useful when contemplating dose escalation to minimize the volume of bladder and rectum included in the treatment fields.

Adenocarcinoma↗
PubMed1995

Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum.

OBJECTIVE: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group. SUMMARY BACKGROUND DATA: The optimal treatment of large rectal carcinomas remains controversial; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. METHODS: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy-proven lesions > 3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates. RESULTS: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens. Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes. In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (< 5%). Cox-Mantel analysis of Kaplan-Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p = 0.031) for protocol versus control patients. CONCLUSIONS: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.

Adenocarcinoma↗
PubMed1995

Elevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor.

OBJECTIVE: The authors determined whether untreated breast cancer patients have elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1). SUMMARY BACKGROUND DATA: Increased plasma TGF-beta 1 levels recently were found after chemotherapy in patients with advanced breast cancer. However, it currently is unknown whether this elevation in plasma TGF-beta 1 is caused by chemotherapy-induced normal tissue damage or whether it results from the presence of the tumor. METHODS: An enzyme-linked immunosorbent assay was used to measure plasma TGF-beta 1 levels in 26 newly diagnosed breast cancer patients before and after definitive surgery. Patients were grouped by postoperative tumor status: 1) negative lymph nodes (group 1); 2) positive lymph nodes (group 2); and 3) overt residual disease (group 3). The site of TGF-beta 1 production in the tumors was localized by immunohistochemistry and in situ hybridization. RESULTS: Plasma TGF-beta 1 levels were elevated preoperatively in 81% of the patients; TGF-beta 2 and TGF-beta 3 were undetectable. The preoperative TGF-beta 1 levels in the three patient groups were similar; however, the postoperative plasma TGF-beta 1 levels differed by disease status. The mean plasma TGF-beta 1 level in group 1 (n = 12) normalized after surgery (19.3 +/- 3.2 vs. 5.5 +/- 1.0 ng/mL, p < 0.001). In contrast, the mean plasma TGF-beta 1 levels remained above normal in both group 2 (n = 9) and group 3 (n = 5) after surgery. Transforming growth factor-beta 1 expression was found to be preferentially increased in the tumor stroma. CONCLUSIONS: Breast tumors result in increased plasma TGF-beta 1 levels in 81% of patients. After surgical removal of the primary tumor, the plasma TGF-beta 1 level normalizes in the majority of patients; persistently elevated levels correlate with the presence of lymph node metastases or overt residual tumor. These findings suggest that the usefulness of TGF-beta 1 as a potential plasma marker for breast tumors deserves further study.

Biomarkers, Tumor↗
PubMed1995

Short communication: normal tissue injury after cancer therapy is a local response exacerbated by an endocrine effect of TGF beta.

The sensitivity of normal tissues rather than of the tumour usually limits the effectiveness of cancer treatment. The normal tissue side effects from chemotherapy and/or radiotherapy result from both direct cellular loss and the extensive fibrosis that develops at the site of injury. Recent evidence suggests that the cytokine, transforming growth factor beta (TGF beta), mediates this fibrogenic process. Herein, we provide evidence in support of the hypothesis that the fibrosis formation following therapy results not only from TGF beta produced locally in the injured normal tissue, but also from circulating TGF beta released by the tumour. Thus, therapy-induced normal tissue damage appears in part to be a local manifestation of a systemic condition.

Antineoplastic Agents↗
PubMed1995

Changes in plasma transforming growth factor beta in response to high-dose chemotherapy for stage II breast cancer: possible implications for the prevention of hepatic veno-occlusive disease and pulmonary drug toxicity.

Veno-occlusive disease (VOD) of the liver and pulmonary drug toxicity (PDT) are two major complications of high-dose chemotherapy and autologous bone marrow transplantation (BMT) for solid tumors. We have previously demonstrated that an elevated plasma TGF-beta concentration before transplant predicts the later occurrence of these complications. In the present study, we used a simplified enzyme-linked immunosorbant assay (ELISA) to prospectively evaluate the kinetics of plasma TGF-beta concentrations of 45 patients with stage II breast cancer who underwent high-dose chemotherapy and autologous BMT. We demonstrated that, of the three TGF-beta isoforms, only TGF-beta 1 was present in the plasma. Pre-transplant plasma TGF-beta 1 was significantly higher in patients with VOD and PDT compared with that in patients without these complications. The plasma TGF-beta 1 level in patients who later developed VOD or PDT decreased to that of controls within 2 days of initiating high-dose chemotherapy; this decrease was not correlated with platelet concentration changes. These results suggest that interventions aimed at preventing the development at VOD or PDT must be given early in the course of high-dose chemotherapy.

Adenocarcinoma↗
PubMed1994

Changes in plasma TGF beta levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis.

PURPOSE: To determine whether plasma transforming growth factor-beta (TGF-beta) levels measured before and during radical radiotherapy for lung cancer could be used to predict patients at risk for the development of radiation pneumonitis. METHODS AND MATERIALS: The first eight patients with lung cancer (nonsmall cell: seven, small cell: one) enrolled in a prospective study designed to evaluate physiological and molecular biologic correlates of radiation induced normal tissue injury are described. The study began in June 1991. All patients were treated with radiotherapy with curative intent. Plasma transforming growth factor-beta levels were obtained before, weekly during, and at each follow-up after treatment. Pretreatment pulmonary function tests and single photon emission computed tomography scans were obtained to assess baseline lung function and were repeated at follow-up visits. Dose-volume histogram analyses were performed to determine the volume of lung which received > or = 30 Gy. Patients were assessed at each follow-up visit for signs and symptoms of pneumonitis. RESULTS: Five patients developed signs and/or symptoms of pulmonary injury consistent with pneumonitis and three patients did not. In all three patients not developing pneumonitis, plasma TGF-beta levels normalized by the end of radiotherapy. In contrast, four out of five patients who suffered pneumonitis had persistently elevated plasma TGF-beta levels by the end of therapy. This finding appeared to be independent of the volume of irradiated lung. CONCLUSIONS: These results suggest that plasma TGF-beta levels during treatment may be useful to determine which patients are at high risk of developing symptomatic pneumonitis following thoracic radiotherapy. This finding may have implications when planning additional therapy (either chemotherapy or radiotherapy) which may have potentially adverse consequences on the lung.

Adult↗
PubMed1992

Topical application of WR-2721 to prevent radiation-induced proctosigmoiditis. A phase I/II trial.

Patients undergoing x-ray therapy to the pelvis have intestinal symptoms proportional to the volume treated and the dose delivered. WR-2721, S-2 (3-aminopropylaminoethyl) phosphorothioic acid, is an organic thiophosphate compound that selectively protects normal tissues against radiation effects. A Phase I/II study was done to test the ability of topical application of WR-2721 to protect the mucosa of the rectosigmoid from radiation damage. Thirty-one patients were enrolled in this study, of which, seven were control subjects. Twenty-four patients received WR-2721 daily, in enema form, 45 minutes before treatment. The patients were assigned by groups of three to receive increasing doses of WR-2721 beginning with 100 mg/enema to 450 mg/enema. Rectal mucosal biopsies were obtained within the treated field before, during, and at the end of therapy. The degree of damage to the rectal mucosa was scored on the basis of a 0 to 4 scale (with 0, least damage to 4, most damage) as determined by the percentage of damaged mucosal crypt glands. The patients' symptoms were recorded once a week during the entire course of therapy. The biopsy scores of the control group were slightly higher than those of the treatment groups; however, this difference did not appear to be significant. In the treated groups, there was a slight decrease in the biopsy scores with increasing doses of WR-2721, but this trend was not sustained. There were no differences among any of the groups in the symptoms experienced during the course of therapy. This study showed that WR-2721 could be administered safely in enema form in doses ranging from 100 to 450 mg/enema, but this drug did not protect the rectosigmoid mucosa from radiation damage at the doses administered.

Administration, Topical↗
PubMed1992

Prognostic significance of extent of nodal involvement in stage D1 prostate cancer treated with radiotherapy.

The records of 107 patients with newly diagnosed adenocarcinoma of the prostate irradiated with curative intent at Duke University Medical Center from 1970 through 1983 were reviewed. Forty patients (37%) underwent standard bilateral pelvic lymph node dissection (PLND) prior to beginning irradiation. Twenty-four patients (22%) were found to have pelvic nodal metastases (Stage D1). Those found to have a single microscopically positive node at PLND may be curable with irradiation. In contrast, those with more extensive nodal metastases appear to be incurable with radiotherapy. Additional studies are needed to confirm or refute these findings.

Adenocarcinoma↗
PubMed1992

Radiotherapy for prostate cancer: should the seminal vesicles be considered target?

During radiotherapy for prostate cancer, the ability to predict occult seminal vesicle invasion is important since irradiation of the entire seminal vesicles necessitates enlarging the radiation fields beyond what is usually used to irradiate the prostate gland alone. We analyzed the records of 302 patients with clinical Stage T1 or T2 adenocarcinoma of the prostate treated with radical surgery at Duke University Medical Center between 1970 and 1983. Univariate and multivariate analyses were used to examine the relationship between the risk of occult seminal vesicle involvement (defined herein as histologic involvement of the seminal vesicles not detected by physical or radiologic examination) and the following factors: histologic grade, age, clinical stage, and preoperative acid phosphatase. Among 249 patients with complete information, increasing histologic grade (p < 0.001) and clinical stage (p < 0.04) were found to be the strongest predictors of occult seminal vesicle invasion. Conversely, seminal vesicle invasion was very unusual in well-differentiated T1-T2 tumors (6%). This low risk group represented 28% (70/249) of this patient population. There appears to be a substantial subset of patients with well differentiated T1 or T2 tumors who are at very low risk for occult seminal vesicle involvement and in whom the seminal vesicles can be excluded from the target volume. The reduction in target volume may reduce normal tissue reactions, facilitate dose escalation, and possibly increase local control rates.

Adenocarcinoma↗
PubMed1992

Phase I/II study of external radio frequency phased array hyperthermia and external beam radiotherapy in the treatment of prostate cancer: technique and results of intraprostatic temperature measurements.

As part of an ongoing Phase I/II study at Duke University Medical Center investigating the toxicity and efficacy of external beam radiotherapy plus hyperthermia for deep-seated, locally advanced or recurrent solid tumors, 12 patients with prostate malignancies (adenocarcinoma--11, leiomyosarcoma--1) were treated with radiotherapy plus hyperthermia. Hyperthermia was given after radiotherapy using a Radio Frequency Phase/Amplitude Control Sigma 60 annular phased array device. All patients had simultaneous temperature measurements made in the rectal lumen and within the prostate during at least one hyperthermia session. Intraprostate thermometers were placed via a unique method described herein using both computerized tomography scan and a rigid sigmoidoscope for guidance. We were able to achieve the desired tumor temperature of > or = 42.5 degrees C in only 1/28 (3.5%) of hyperthermia treatments. Subjective symptoms of pain and/or pressure limited power deposition in 79% of hyperthermia treatments. Higher temperatures were achieved in the distal rectum than in the prostate in all treatments, although the differences were not statistically significant. This temperature differential could not be compensated by using phase and amplitude steering. Rectal temperatures adjacent to the prostate were predictive of prostate temperatures. We conclude that using this regional heating technique we were unable to demonstrate an ability to get an advantageous temperature differential between the prostate and normal tissue. This technique is not useful as an adjuvant to radiation therapy for prostate cancer. The usefulness of other regional heating techniques and devices should be explored.

Adenocarcinoma↗
PubMed1992

The role of radiotherapy in patients with advanced seminomatous germ cell tumors. Controversies in management. Part 2.

The role of radiotherapy in the management of advanced seminomatous germ cell tumors remains controversial. The authors review the available literature, and recommend radiotherapy for stage II seminoma with bulky abdominal metastases (greater than 10 cm) under the following circumstances: As primary therapy only if the patient cannot or will not be treated with chemotherapy; as an adjuvant following chemotherapy in patients with residual masses of any size. Similar recommendations are made regarding the role of radiotherapy in the management of extragonadal seminoma outside the central nervous system.

Dysgerminoma↗
PubMed1992

Radiation therapy for testicular seminoma: controversies in the management of early-stage disease.

Subdiaphragmatic irradiation remains the standard treatment for patients with stage I and IIA testicular seminoma. Elective mediastinal irradiation is not indicated. In well-selected patients with stage I disease, aggressive surveillance may be a reasonable alternative to elective irradiation. We believe that bipedal lymphangiography is useful in staging, radiation field design, and follow-up. Other controversies in the radiotherapeutic management include the optimal radiation dose and appropriate target volume.

Dysgerminoma↗
PubMed1991

Multivariate analysis of factors predicting local relapse after radical prostatectomy--possible indications for postoperative radiotherapy.

Between 1970 and 1983, 273 patients underwent radical surgery (radical prostatectomy--261, radical cystoprostatectomy--12) for newly diagnosed adenocarcinoma of the prostate at Duke University Medical Center and received no adjuvant radiotherapy. A total of 46 patients developed local recurrence. Forty developed local relapse only and six developed simultaneous local and distant failure. The crude local relapse rate was 17% (46/273). The actuarial local failure rate at 5, 10, and 15 years was 12%, 32%, and 35%, respectively. Univariate and multivariate analyses were performed to identify factors predictive of local relapse after radical surgery. Possible prognostic factors analyzed were: age, type of biopsy, use of adjuvant hormonal therapy, histologic grade, histologic involvement of seminal vesicles, positive surgical margins, clinical stage, and elevated acid phosphatase. Factors identified as significant predictors of local relapse by univariate analysis were: poorly differentiated histology (p = 0.0001), seminal vesicle involvement (p = 0.0009), and positive surgical margins (p = 0.0001). An elevated preoperative acid phosphatase was of borderline significance (p = 0.06). On multivariate analysis, poorly differentiated histology (p = 0.0007), positive margins (p = 0.0015), and elevated acid phosphatase (p = 0.0273) were significant predictors of local failure. Seminal vesicle involvement was no longer a significant predictor of local failure. However, on subsequent univariate and multivariate analyses, seminal vesicle involvement was the only significant predictor for the development of distant metastases (p = 0.0019, multivariate). Thus, patients with poorly differentiated tumors, positive surgical margins, or elevated preoperative acid phosphatase are at high risk for local relapse after radical prostatectomy. These patients should be included in future clinical trials studying the role of adjuvant radiotherapy after radical prostatectomy, or offered adjuvant radiotherapy if they cannot or will not participate in such trials.

Adenocarcinoma↗
PubMed1991

Transurethral resection of prostate prior to definitive irradiation for prostate cancer. Lack of correlation with treatment outcome.

From 1970 through 1983, 107 patients with newly diagnosed adenocarcinoma of the prostate were treated with radiotherapy with curative intent at Duke University Medical Center. Forty-five patients (42%) underwent transurethral resection of the prostate (TURP) for diagnostic and/or therapeutic purposes prior to beginning radiotherapy. Sixty-one patients (57%) were diagnosed by needle biopsy. TURP and needle biopsy groups were comparable (age, elevated acid phosphatase, early [A2, B] and late [C, D1] disease stages, and follow-up). TURP patients were more likely to have poorly differentiated tumors and were more often given concurrent hormonal therapy. Both univariate and multivariate analyses to study the effect of TURP on patients with prostate cancer treated with radiotherapy were done. We were unable to demonstrate any adverse impact of TURP on the outcome of radiation therapy for prostate cancer. This issue remains controversial and should be addressed in a prospective, randomized trial.

Actuarial Analysis↗