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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
PubMed1998

Radiotherapy alone for medically inoperable stage I non-small-cell lung cancer: the Duke experience.

PURPOSE: To review our experience treating clinical Stage I non-small-cell lung carcinoma with radiotherapy alone using modern techniques and staging. The effect of dose and volume on outcome is to be analyzed. METHODS: Between January 1980 and December 1995, 156 patients with Stage I medically inoperable non-small-cell lung cancer were irradiated at Duke University Medical Center and the Durham Veterans Administration Medical Center. Fifteen patients were excluded from analysis (7 treated with palliative intent, and 8 lost to follow-up immediately following radiation). Characteristics of the 141 evaluable patients were as follows: Median age 70 years (range 46-95); gender: male 83%, female 17%; institution: DUMC 65%, DVAMC 35%; T1N0 54%, T2N0 46%; median size 3 cm (range 0.5 to 8); pathology: squamous cell carcinoma 52%, adenocarcinoma 18%, large cell carcinoma 19%, not otherwise specified 11%; presenting symptoms: weight loss 26%, cough 23%, none (incidental diagnosis) 57%. All patients underwent simulation prior to radiotherapy using linear accelerators of > or = 4 MV. No patients received surgery or chemotherapy as part of their initial treatment. The median dose of radiotherapy (not reflecting lung inhomogeneity corrections) was 64 Gy (50 to 80 Gy) given in 1.2 bid to 3 Gy qid fractionation. The majority of cases included some prophylactic nodal regions (73%). RESULTS: Of the 141 patients, 108 have died; 33% of intercurrent death, 35% of cancer, and 7% of unknown causes. At last follow-up, 33 patients were alive (median 24 months, range 7-132 months). The 2- and 5-year overall survival was 39% and 13%, respectively (median 18 months). The corresponding cause-specific survival was 60%, and 32% (median 30 months). On multivariate analysis, significant factors influencing overall and/or cause-specific survival were age, squamous cell histology, incidental diagnosis, and pack-years of smoking. There was a nonsignificant trend towards improved cause-specific survival with higher radiotherapy doses and larger treatment volumes. On patterns of failure analysis, 42% of failures were local-only and 38% were distant-only. Regional-only failure occurred in 4 patients (7%), 3 of whom failed solely in an unirradiated nodal site. Analysis of factors correlating with local failure at 2 years was performed using a multinominal logistic regression analysis. Significant factors associated with a lower local failure included incidental diagnosis and absence of cough with a strong trend toward significance for higher radiotherapy dose (p = 0.07) and larger treatment volume (p = 0.08). Patients who were locally controlled had an improved cause-specific survival at 5 years over those who were not controlled (46% vs. 12%, p = 0.03). Grade III-V complications occurred in 2 patients (1.5%). CONCLUSION: Patients with clinical Stage I medically inoperable non-small-cell lung cancer treated with contemporary radiotherapy alone achieved a 5-year cause-specific survival of 32%. Uncontrolled lung cancer was the primary cause of death in these patients, and local failure alone represented the most common mode of failure (42%). Patients who were locally controlled had a significantly improved cause-specific survival over those who failed locally. Because higher doses of radiotherapy appear to provide improved local control, studies of dose escalation are warranted until dose-limiting toxicity is observed.

Adenocarcinoma↗
PubMed1998

The relevance of transforming growth factor beta 1 in pulmonary injury after radiation therapy.

The maximum dose of radiation which can be delivered to a tumor is limited by the tolerance of the surrounding normal tissues. The ability to identify patients at high or low risk of injury from radiation therapy might enable the clinician to tailor radiation doses in order to maximize efficacy and minimize risk. The cytokine transforming growth factor beta 1 (TGF beta 1) has been implicated in the development of normal tissue injury after irradiation in several organs, including the lung. Herein, the evidence supporting the role of TGF beta 1 in radiation-induced lung injury is reviewed. Using the treatment of non-small cell lung cancer as a model, we also discuss how it may be possible to identify patients at risk for this complication using measurements of plasma TGF beta 1, and how this information may be used in the future to adjust doses of radiation in the treatment of lung cancer.

Animals↗
PubMed1997

Combined external beam irradiation and external regional hyperthermia for locally advanced adenocarcinoma of the prostate.

PURPOSE: To determine the safety and efficacy of combined external beam irradiation and external regional hyperthermia in the treatment of adenocarcinoma of the prostate. METHODS AND MATERIALS: From 1987 to 1994, 30 patients received combined external beam irradiation and external regional hyperthermia for locally advanced prostate cancer. The results of the 21 patients with newly diagnosed (n = 18) or locally recurrent (n = 3) adenocarcinoma are reported herein. No patient had evidence of distant metastases. Total radiotherapy doses of 65-70 Gy to the prostate were planned using a four-field box technique. Hyperthermia treatments were delivered using an annular phased array microwave device. The treatment goal was to achieve temperatures > or = 42 degrees C in all measured points within the prostate. RESULTS: Of the newly diagnosed patients, 16 out of 18 (89%) had T3 or T4 tumors, 11 out of 18 (61%) had Gleason scores of 7-9, and the mean pretreatment Prostate Specific Antigen (PSA) was 69 ng/ml. The median follow-up of all 21 patients was 36 months. None of the patients achieved the treatment goal of all intratumoral temperatures > or = 42 degrees C. The mean CEM 43 T90 was 2.34 min. The disease-free survival at 36 months is 25%; 12 out of 18 (67%) of the patients have relapsed. The only significant predictor of relapse was pretreatment PSA. There were no complications > Grade 3. CONCLUSIONS: In spite of the inability to achieve high tumor temperatures, the relapse-free survival rate in this population of patients with very advanced localized prostate cancer treated with radiation therapy plus hyperthermia compares favorably with most series using radiation therapy alone. Further studies aimed at improving the ability to deliver hyperthermia to the prostate are warranted.

Adenocarcinoma↗
PubMed1997

Changes in plasma transforming growth factor beta during radiotherapy and the risk of symptomatic radiation-induced pneumonitis.

PURPOSE: To determine whether changes in the plasma Transforming Growth Factor beta1 (TGF beta1) concentration during radiotherapy could identify patients at risk for developing symptomatic radiation pneumonitis. METHODS AND MATERIALS: Thirty-six patients who received radiation therapy with curative intent for lung cancer (n = 31), Hodgkin's disease (n = 4), or thymoma (n = 1) were evaluated prospectively. All patients had serial plasma TGF beta1 measurements obtained before, during, and after treatment. Plasma TGF beta1 was quantified using an enzyme-linked immunosorbent assay. Pneumonitis was defined clinically. Plasma TGF beta1 levels were considered to have normalized if the following occurred: the last on-treatment TGF beta1 level was both <7.5 ng/ml and lower than the pretreatment level. RESULTS: Thirteen of these 36 patients developed pneumonitis. Significant changes in plasma TGF beta1 levels during treatment were seen only in the subset of patients whose TGF beta1 levels were >7.5 ng/ml at baseline (n = 22). Failure of plasma TGF beta1 to normalize by the end of treatment, as defined above, much more accurately identified patients at risk for symptomatic pneumonitis if their baseline TGF beta1 was >7.5 ng/ml than if it was <7.5 ng/ml. CONCLUSIONS: Changes in plasma TGF beta1 levels during radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic radiation pneumonitis, particularly in the subset of patients whose pretreatment TGF beta1 levels are >7.5 ng/ml.

Biomarkers↗
PubMed1996

Plasma transforming growth factor-beta 1 reflects disease status in patients with lung cancer after radiotherapy: a possible tumor marker.

PURPOSE: To determine the frequency with which elevated plasma transforming growth factor-beta 1 (TGF beta 1) concentrations occur in lung cancer patients, to determine the kinetics of TGF beta 1 expression during and after radiotherapy and to correlate plasma TGF beta 1 levels with disease status after treatment. MATERIALS AND METHODS: Plasma samples were obtained before, during and after radiotherapy in 54 patients with lung cancer and 20 normal controls. Plasma TGF beta 1 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Baseline TGF beta 1 levels in lung cancer patients and normal controls were 13.0 +/- 2.5 and 4.4 +/- 0.3 ng/ml, respectively. Elevated TGF beta 1 were found in 50% (27/54) of lung cancer patients. During radiation therapy plasma TGF beta 1 levels declined, however, by the completion of treatment the mean TGF beta 1 level had not normalized in patients with lung cancer. The TGF beta 1 level at last follow-up correlated with disease status in those patients with an increased pretreatment plasma level. Three of four patients with no evidence of cancer had normal follow-up TGF beta 1 levels, compared to 2/16 patients with residual or recurrent tumor (P = 0.02). CONCLUSIONS: Elevated plasma TGF beta 1 levels occur frequently in patients with lung cancer. In those patients with an elevated plasma TGF beta 1 level at diagnosis, monitoring this level may be useful in detecting both disease persistence and recurrence after therapy.

Aged↗
PubMed1996

Positron emission tomography in the pretreatment evaluation and follow-up of non-small cell lung cancer patients treated with radiotherapy: preliminary findings.

The purpose of this study was to prospectively evaluate positron emission tomography (PET) for delineating lung cancers preradiotherapy and to assess PET's ability to distinguish residual tumor from scarring following radiotherapy. Between April 1991 and October 1992, 20 patients underwent 18fluoro-2-deoxyglucose (18FDG) PET scanning of the chest prior to radiotherapy for lung cancer. Tumor volumes on chest x-ray (CXR) and computerized tomography (CT) scan were correlated with abnormalities on PET scans. Follow-up PET studies were compared to postradiotherapy chest x-ray and/or CT scans, and correlated with clinical outcome. Six of seven well-demarcated tumors showed increased uptake of 18FDG correlating with the CT/CXR tumor volume. Twelve poorly demarcated tumors demonstrated increased 18FDG uptake. In seven of 12, the CT/CXR abnormality correlated with changes on PET scan. In three of 12, CT/CXR abnormalities were larger than on PET, whereas in two of 12, abnormalities on PET extended outside the region of CT/CXR changes. The 13th patient in the poorly demarcated category had diffuse carcinoma in situ at the surgical margin that demonstrates increased 18FDG uptake, but was not visible by CT/CXR. Of 12 patients with follow-up studies, all had changes on CXR and/or CT that made it difficult to assess response. Four of 12 had a complete response by PET; all remain locally controlled. The remaining eight patients had either a partial response (n = 6) or no response (n = 2) by PET. Four of these eight patients remain alive and well 11-24 months after therapy. 18FDG PET may be useful for delineation of lung cancer volumes that are poorly defined by CXR and/or CT scan. The value of PET in differentiating tumor from fibrosis after radiotherapy for lung cancer remains to be established.

Carcinoma in Situ↗
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

Prostate bed massage as a means to determine the source of a rising prostate specific antigen after radical prostatectomy.

PURPOSE: To determine the value of prostate bed massage as a means to determine whether a rising prostate specific antigen (PSA) after radical prostatectomy is due to local recurrence or distant metastases. METHODS AND MATERIALS: Eighteen patients referred for pelvic radiotherapy because of a rising PSA after radical prostatectomy had PSA levels measured immediately before and 5 minutes after a vigorous 30-second massage of the prostate bed. RESULTS: Only one of the 18 (5%) patients experienced a rise in their PSA following vigorous prostate bed massage. Fifteen of the 18 (83%) patients' PSA levels declined after radiotherapy, suggesting that recurrent prostate cancer had been present in the prostate bed at the time of prostate massage in these patients. Only 1 of these 15 patients (7%) had a rise in their PSA after massage. CONCLUSION: Prostate bed massage, as performed in this study, was not helpful to determine whether a rise in PSA after radical prostatectomy was due to local or distant recurrence.

Humans↗
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↗