Biomedical subjects

B W Corn

Publications and source records attributed to B W Corn.

At least 19 recordsLinked to original sources

PubMed2001

Stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of acoustic schwannomas: comparative observations of 125 patients treated at one institution.

BACKGROUND: Stereotactic radiosurgery (SRS) and, more recently, fractionated stereotactic radiotherapy (SRT) have been recognized as noninvasive alternatives to surgery for the treatment of acoustic schwannomas. We review our experience of acoustic tumor treatments at one institution using a gamma knife for SRS and the first commercial world installation of a dedicated linac for SRT. METHODS: Patients were treated with SRS on the gamma knife or SRT on the linac from October 1994 through August 2000. Gamma knife technique involved a fixed-frame multiple shot/high conformality single treatment, whereas linac technique involved daily conventional fraction treatments involving a relocatable frame, fewer isocenters, and high conformality established by noncoplanar arc beam shaping and differential beam weighting. RESULTS: Sixty-nine patients were treated on the gamma knife, and 56 patients were treated on the linac, with 1 NF-2 patient common to both units. Three patients were lost to follow-up, and in the remaining 122 patients, mean follow-up was 119 +/- 67 weeks for SRS patients and 115 +/- 96 weeks for SRT patients. Tumor control rates were high (> or =97%) for sporadic tumors in both groups but lower for NF-2 tumors in the SRT group. Cranial nerve morbidities were comparably low in both groups, with the exception of functional hearing preservation, which was 2.5-fold higher in patients who received conventional fraction SRT. CONCLUSION: SRS and SRT represent comparable noninvasive treatments for acoustic schwannomas in both sporadic and NF-2 patient groups. At 1-year follow-up, a significantly higher rate of serviceable hearing preservation was achieved in SRT sporadic tumor patients and may therefore be preferable to alternatives including surgery, SRS, or possibly observation in patients with serviceable hearing.

Adult↗

PubMed2001

Memory performance used to detect radiation effects on cognitive functioning.

Although radiotherapy remains a necessary and frequently used treatmentfor brain tumors, uncertainty remains about the nature and severity of neurocognitive morbidity. We show that verbal-semantic memory (free recall of word list) is sensitive to damaging radiation effects in 20 patients with low-grade, supratentorial, primary brain tumors who received moderate doses of partial-brain irradiation. We previously reported that verbal-semantic memory is dissociated from visual memory (acquisition and recall) during the same phase ofradiation effects, indicating that memory is differentially affected by radiation. In this study, we provide evidence of the nature of the iatrogenic radiation effect on memory by testing collateral cognitive functions that might explain the specific memory impairment. We found that the verbal-semantic recall impairment was not associated with impairments in auditory attention, auditory processing speed, auditory-verbal working memory, or in the temporal coding or subjective organization of word-list recall. These findings focus damaging radiation effects on primary retrievalprocesses, rather than on earlier cognitive processes or executive processes affecting recall. Knowledge of the specific patterns of change in cognition would guide the differential diagnosis and rehabilitation of survivors of brain tumors whose conditions are complicated by tumors with multiple treatments.

Adult↗

PubMed2000

Strong correlation between imaging response and survival among patients with primary central nervous system lymphoma: a secondary analysis of RTOG studies 83-15 and 88-06.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is the brain tumor with the most rapidly increasing incidence, yet little is known about its radiographic response to cranial irradiation. If traditionally used doses of radiotherapy ( approximately 60 Gy) are associated with low rates of complete response and poor survival, then an argument can be made to consider dose escalation of radiotherapy. Alternatively, if poor survival rates are associated with high rates of complete response, there would be no reason to subject patients to higher radiation doses with increased risks of treatment-related morbidity. The purpose of this analysis is to provide a detailed review of response following cranial irradiation. Based on these findings, recommendations are offered for future protocol design. METHODS AND MATERIALS: Patients were treated on either RTOG 83-15 (whole brain irradiation to 40 Gy followed by a 20 Gy boost to the tumor plus 2-cm margin) or RTOG 88-06 (induction cyclophosphamide, doxorubicin, vincristine, dexamethasone [CHOD] followed by whole brain irradiation to 41.4 Gy and an 18 Gy tumor boost). Imaging surveillance (CT, MR) was required following surgery, prior to the initiation of RT and following completion of RT. Complete response referred to the absence of enhancement on follow-up scans in comparison to the pretherapy study. A tumor size reduction of at least 50% in the product of the largest cross-sectional diameter and its largest perpendicular diameter was scored as a partial response. RESULTS: Seventy-nine patients had scans available for central review. Complete response was achieved in 83% and 85% of patients treated on RTOG 83-15 and 88-06, respectively. The rates of partial response (14%, 11%) and radiographic progression (3%, 4%) also were comparable between the studies. For survival analyses, data were aggregated from the two studies. The 4-year survival rates were 24% for complete responders versus 11% for other patients (p = 0.0006). In multivariate analysis, only complete radiographic response (p < 0.0007), and high Karnofsky performance status (KPS >/= 70) (p < 0.005) were independently associated with increased rates of 4-year survival. CONCLUSION: A high rate of complete radiographic response was observed following moderate doses of cranial irradiation (alone or in combination with CHOD chemotherapy). Although complete responders had a statistically significant survival advantage at 4 years when compared with partial responders and nonresponders, the majority of patients who achieved complete response were dead of disease by 4 years following treatment. Based on this analysis of the RTOG database, there is no rationale for radiation dose escalation as a therapeutic strategy to combat PCNSL. Consequently, the radiotherapy component of the current RTOG Phase II trial (RTOG 93-10) now includes relatively low total doses of hyperfractionated irradiation for patients without residual disease (36 Gy/1.2 Gy, twice a day) as well as a more aggressive chemotherapy regimen.

Adult↗

PubMed2000

Radiotherapeutic effects on brain function: double dissociation of memory systems.

OBJECTIVE: The neurocognitive sequelae of therapeutic cranial irradiation are not well characterized in adults with primary brain tumors. To address this problem, we prospectively examined neuropsychological findings during two phases of radiation effects. BACKGROUND: Investigations of radiation effects have revealed variable outcomes that range from no radiation-associated morbidity to severe cognitive impairment, but have relied on case reports or retrospective studies of late-delayed changes in white matter or in cognition. No reliable radiographic or neurocognitive tools exist to describe the multiple phases of radiation effects. METHOD: Twenty adult patients (median age, 39 years) from a university hospital were treated with radiotherapy (RT) for low-grade primary brain tumors. Prospective longitudinal neuropsychological studies were compared at baseline (after surgery and before irradiation) and at 3, 6, and 12 months after RT to examine early-delayed effects, including verbal memory changes in 20 patients and visual memory changes in 11 patients. We also examined cognitive changes during the late-delayed phase for up to 3 years after RT and determined whether early-delayed memory deficit predicted late-delayed memory deficit in a small subset of patients. A comprehensive neuropsychological battery was used, including verbal and visual memory tests designed to compare learning, storage, and retrieval. RESULTS: Patients demonstrated normal verbal memory at baseline, decrement, and then rebound in verbal retrieval. Deficit at baseline and recovery up to 1 year after RT defined visual memory. Together, these observations constitute a double dissociation of memory functions. No changes over time were observed in other neurocognitive tests or in fatigue or mood measures. Time-dependent patterns of each long-term memory test were examined in relation to lesion site in individual patients. CONCLUSIONS: The double dissociation of memory functions after RT may provide markers for the damaging and facilitative early-delayed effects of RT. Late-delayed effects were not predicted based on early-delayed changes in a small sample.

Adult↗

PubMed1999

Variation of clinical target volume definition in three-dimensional conformal radiation therapy for prostate cancer.

PURPOSE: Currently, three-dimensional conformal radiation therapy (3D-CRT) planning relies on the interpretation of computed tomography (CT) axial images for defining the clinical target volume (CTV). This study investigates the variation among multiple observers to define the CTV used in 3D-CRT for prostate cancer. METHODS AND MATERIALS: Seven observers independently delineated the CTVs (prostate +/- seminal vesicles [SV]) from the CT simulation data of 10 prostate cancer patients undergoing 3D-CRT. Six patients underwent CT simulation without the use of contrast material and serve as a control group. The other 4 had urethral and bladder opacification with contrast medium. To determine interobserver variation, we evaluated the derived volume, the maximum dimensions, and the isocenter for each examination of CTV. We assessed the reliability in the CTVs among the observers by correlating the variation for each class of measurements. This was estimated by intraclass correlation coefficient (ICC), with 1.00 defining absolute correlation. RESULTS: For the prostate volumes, the ICC was 0.80 (95% confidence interval [CI]: 0.56-0.96). This changed to 0.92 (95% CI: 0.75-0.99) with the use of contrast material. Similarly, the maximal prostatic dimensions were reliable and improved. There was poor agreement in defining the SV. For this structure, the ICC never exceeded 0.28. The reliability of the isocenter was excellent, with the ICC exceeding 0.83 and 0.90 for the prostate +/- SV, respectively. CONCLUSIONS: In 3D-CRT for prostate cancer, there was excellent agreement among multiple observers to define the prostate target volume but poor agreement to define the SV. The use of urethral and bladder contrast improved the reliability of localizing the prostate. For all CTVs, the isocenter was very reliable and should be used to compare the variation in 3D dosimetry among multiple observers.

Humans↗

PubMed1999

A dynamic model for the estimation of optimum timing of computed tomography scan for dose evaluation of 125I or 103Pd seed implant of prostate.

PURPOSE/OBJECTIVE: The dosimetric evaluation of permanent 125I or 103Pd prostate implant is based on the assumption that both prostate and seeds are static throughout the entire treatment time which lasts months. However, the prostate is often edematous after the surgical implantation of seeds. Therefore, both the volume of the prostate and the seed locations change dynamically as the edema resolves. This effect has impact on the validity of postimplant analysis based upon a CT scan. If a CT scan is taken too early after implantation while there is edema in the prostate, the dose delivered by the implant may be underestimated. If the imaging is delayed too long, the dose may be overestimated. The magnitude of this effect depends on both of the half-life of the isotope used and the half-life and magnitude of the edema. This study describes a dynamic biomathematical model which takes edema into account in calculating the dose delivered by the implant and is used to investigate the optimum time to obtain the postimplant CT scan. MATERIALS AND METHODS: The dynamic biomathematical model is a numerical integration of the accumulated dose in which the prostate dimensions, the seed locations, and the source strength are all functions of time. The function which describes the change in prostate dimensions and seed locations as a function of time was determined in a separate study by analysis of serial postimplant CT scans. Dose-volume histograms (DVH) of the prostate for the total dose generated by the dynamic model are compared to DVHs generated by CT scans simulated for postimplant intervals ranging from 0 to 300 days after the implantation for 30 different combinations of the magnitude and duration of edema. RESULTS: DVHs of the prostate calculated by taking edema into account show that the time of obtaining a CT scan for postimplant analysis is critical to the accuracy of dose evaluations. The comparison of the DVHs generated by the dynamic model to those generated by the CT scans simulated for a range of postimplant intervals show that obtaining the CT scan too early tends to underestimate the total dose while obtaining the CT scan after the edema is resolved tends to overestimate it. The results show that the optimum timing of the CT scan depends upon the duration of the edema and the half-life of the radioisotope used. It is almost independent of the magnitude of the edema. Thus, a unique optimum time window for the imaging study cannot be defined for either 125I or 103Pd implants. However, an optimum time window can be identified for which the calculated dose, on the average, will generally differ from the actual dose by less than 5%, with a maximum error not exceeding 15%. Such a window is 4 to 10 weeks after the implantation for an 125I implant, and 2 to 4 weeks for a 103Pd implant. CONCLUSIONS: A dynamic biomathematical model to correct for the effects of edema in calculating the total dose delivered by an 125I or 103Pd seed implant has been developed. The model has been used to investigate the optimum time window during which the postimplant CT scans for analysis should be obtained.

Brachytherapy↗

PubMed1999

Immediate side effects of stereotactic radiotherapy and radiosurgery.

PURPOSE: Despite increased utilization of fractionated stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), the incidence and nature of immediate side effects (ISE) associated with these treatment techniques are not well defined. We report immediate side effects from a series of 78 patients. MATERIALS AND METHODS: Intracranial lesions in 78 adult patients were treated with SRT or SRS, using a dedicated linear accelerator. Those lesions included 13 gliomas, 2 ependymomas, 19 metastatic tumors, 15 meningiomas, 12 acoustic neuromas, 4 pituitary adenomas, 1 optic neuroma, 1 chondrosarcoma, and 11 arteriovenous malformations (AVM). SRT was used in 51 and SRS in 27 patients. Mean target volume was 9.0 cc. Eleven patients received prior external-beam radiation therapy within 2 months before SRT/SRS. Any side effects occurring during and up to 2 weeks after the course of radiation were defined as ISE and were graded as mild, moderate, or severe. The incidence of ISE and the significance of their association with several treatment and pretreatment variables were analyzed. RESULTS: Overall, 28 (35%) of 78 patients experienced one or more ISE. Most of the ISE (87%) were mild, and consisted of nausea (in 5), dizziness/vertigo (in 5), seizures (in 6), and new persistent headaches (in 17). Two episodes of worsening neurological deficit and 2 of orbital pain were graded as moderate. Two patients experienced severe ISE, requiring hospitalization (1 seizure and 1 worsening neurological deficit). ISE in 6 cases prompted computerized tomography of the brain, which revealed increased perilesional edema in 3 cases. The incidence of ISE by diagnosis was as follows: 46% (6 of 13) for gliomas, 50% (6 of 12) for acoustic neuromas, 36% (4 of 11) for AVM, 33% (5 of 15) for meningiomas, and 21% (4 of 19) for metastases. A higher incidence of dizziness/vertigo (4 of 12 = 33%) was seen among acoustic neuroma patients than among other patients (p< 0.01). There was no significant association of dizziness/vertigo with either a higher average and maximum brainstem dose (p = 0.74 and 0.09, respectively) or with 2-Gy equivalents of the average and maximum brainstem doses (p = 0.28 and 0.09, respectively). Higher RT dose to the margin and higher maximum RT dose were associated with a higher incidence of ISE (p = 0.05 and 0.01, respectively). However, when RT dose to the margin was converted to a 2-Gy dose-equivalent, it lost its significance as predictor of ISE (p = 0.51). Recent conventional external-beam radiation therapy, target volume, number of isocenters, collimator size, dose inhomogeneity, prescription isodose, pretreatment edema, dose of prior radiation, fraction size (2.0-7.0 Gy with SRT and 13.0-21.0 Gy with SRS), fractionation schedule, and dose to brainstem were not significantly associated with ISE. ISE occurred in 26% (8) of 31 patients taking corticosteroids prior to SRT/SRS and in 20 (42%) of 47 patients not taking them (p = 0.15). CONCLUSION: ISE occur in one third of patients treated with SRT and SRS and are usually mild or moderate and self-limited. Dizziness/vertigo are common and unique for patients with acoustic neuromas and are not associated with higher brainstem doses. We are unable to detect a relationship between ISE and higher margin or maximum RT doses. No specific conclusion can be drawn with regard to the effect of corticosteroids, used prior to SRS/SRT, on the occurrence of ISE.

Adult↗

PubMed1999

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma.

PURPOSE: A phase I dose escalation of hypofractionated stereotactic radiotherapy (H-SRT) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery (SRS) and brachytherapy. MATERIALS AND METHODS: From November 1994 to September 1996, 25 lesions in 20 patients with clinical and/or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT. Nineteen patients at the time of initial diagnosis had glioblastoma multiforme (GBM) and one patient had an anaplastic astrocytoma. All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy (RT) with a mean and median dose of 60 Gy (44.0-72.0 Gy). The median time from completion of initial RT to H-SRT was 3.1 months (0.7-45.5 months). Salvage H-SRT was delivered using daily 3.0-3.5 Gy fractions (fxs). Three different total dose levels were sequentially evaluated: 24.0 Gy/3.0 Gy fxs (five lesions), 30.0 Gy/3.0 Gy fxs (10 lesions), and 35.0 Gy/3.5 Gy fxs (nine lesions). Median treated tumor volume measured 12.66 cc (0.89-47.5 cc). The median ratio of prescription volume to tumor volume was 2.8 (1.4-5.0). Toxicity was judged by RTOG criteria. Response was determined by clinical neurologic improvement, a decrease in steroid dose without clinical deterioration, and/or radiologic imaging. RESULTS: No grade 3 toxicities were observed and no reoperation due to toxicity was required. At the time of analysis, 13 of 20 patients had died. The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20%. Neurological improvement was found in 45% of patients. Decreased steroid requirements occurred in 60% of patients. Minor imaging response was noted in 22% of patients. Using Fisher's exact test, response of any kind correlated strongly to total dose (p = 0.0056). None of six lesions treated with 21 Gy or 24 Gy responded, whereas there was a 79% response rate among the 19 lesions treated with 30 or 35 Gy. Tumor volumes < or =20 cc were associated with a higher likelihood of response (p = 0.053). CONCLUSIONS: H-SRT used in this cohort of previously irradiated patients with malignant glioma was not associated with the need for reoperation due to toxicity or grade 3 toxicity. This low toxicity profile and encouraging H-SRT dose-related response outcome justifies further evaluation and dose escalation.

Brain Neoplasms↗

PubMed1999

Does androgen suppression enhance the efficacy of postoperative irradiation? A secondary analysis of RTOG 85-31. Radiation Therapy Oncology Group.

OBJECTIVES: To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation (RT) versus RT alone on a group of men after prostatectomy who had indications for adjuvant treatment. METHODS: A national prospective randomized trial (Radiation Therapy Oncology Group [RTOG] 85-31) comparing standard external beam RT plus immediate androgen suppression versus external beam RT alone with delayed hormonal treatment at relapse was initiated for patients with locally advanced adenocarcinoma of the prostate. One hundred thirty-nine of the patients in this trial had indications for adjuvant treatment after prostatectomy (eg, capsular penetration, seminal vesicle involvement). Seventy-one of the patients received RT with immediate androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist); 68 patients received RT alone with hormonal manipulation instituted only at the time of relapse. RESULTS: With a median follow-up of 5 years, the estimated progression-free survival rate (failure defined as prostate-specific antigen [PSA] greater than 0.5 ng/mL) was 65% for the men who received combination therapy and 42% for those treated by RT alone with hormones reserved for relapse (P = 0.002). Differences in the rates of freedom from biochemical relapse were observed when failure was defined as PSA of 1.0 to 3.9 ng/mL (71% versus 46%; P = 0.008) and PSA greater than 4.0 ng/mL (76% versus 55%; P = 0.05), respectively. No differences were observed between the groups with respect to the end points of local control, distant failure, and overall survival. The use of immediate androgen suppression (ie, LHRH agonists) and the absence of pathologic nodal involvement were independently associated with prolongation of freedom from biochemical relapse by multivariate analysis. CONCLUSIONS: Patients with prostate cancer and indications for postoperative RT should be considered for combined RT and hormonal manipulation. Because statistically significant advantages for this experimental approach could not be defined for all end points studied (in particular, overall survival), efforts should be made to enroll these patients in the recently activated RTOG trial (96-01) comparing RT plus placebo to the combination of RT plus Casodex in the postoperative setting.

Adenocarcinoma↗

PubMed1999

Stereotactic Irradiation: potential new treatment method for brain metastases resulting from ovarian cancer.

Stereotactic irradiation (radiosurgery) is a method of precisely focusing well-defined beams of radiation at small intracranial targets. The technique has been applied to the treatment of brain lesions that are benign (e.g., arteriovenous malformations, meningiomas, pituitary adenomas) and malignant (e.g., gliomas, metastases). This paper introduces preliminary data suggesting the possible value of radiosurgery in the management of ovarian cancer metastatic to the brain. Among 32 women with ovarian cancer metastatic to the brain treated with whole brain irradiation, nine (29%) experienced a complete radiographic response, compared with two of the five patients (40%) treated with radiosurgery. The 2-year survival rate was 60% among those treated with radiosurgery and 15% among those who received whole brain irradiation without radiosurgical boost. Stereotactic irradiation may be of clinical benefit to select patients with brain metastases resulting from ovarian cancer. A prospective randomized trial has been implemented by the Radiation Therapy Oncology Group (RTOG 95-08) to determine whether such observations are reproducible on a national scale.

Adult↗

PubMed1999

Palliative treatment of epidemic Kaposi sarcoma of the feet.

Limited information is available in the medical literature on epidemic Kaposi sarcoma (EKS) of the foot. Patients with EKS of the foot can experience severe discomfort that makes it difficult to ambulate and even wear shoes. Between 1985 and 1996, 36 patients with EKS of the foot were treated with palliative intent. Most patients were referred for radiation therapy because of foot discomfort or marked difficulty with ambulation. From the pool of 36 patients, data were available at completion of treatment for 46 sites, and at 1 month for 44 sites. Morbidity was assessed for 35 sites. The median follow-up time for the 44 sites with at least 1 month follow-up was 8 months. The most frequently used regimen was a novel fractionation schedule of three fractions a week at 3.5 Gy/fx to a total dose of 21.0 Gy. The overall response rate and complete response rate for the 44 sites with at least 1 month follow-up were 91% and 80%, respectively. The 46 treated sites evaluated at the completion of treatment had a complete response rate of only 13% and an overall response rate of 63%. Of the 35 sites assessed for acute toxicity, 63% experienced discomfort related to the radiation therapy. This discomfort usually resolved without intervention within 2 weeks of completion of radiation therapy. For patients with and without a history of opportunistic infections, complete responses were observed in 8 of 12 sites (67%) and 25 of 27 sites (93%), respectively (p = 0.06). Radiation therapy for EKS of the foot yields excellent response rates, comparable with responses seen in other cutaneous sites with EKS. Appropriate patient education and support are needed because initial responses to radiation therapy are often disappointing and pedal discomfort can be exacerbated transiently. However, the discomfort resolves and complete response occurs in most patients. The 3.5-Gy triweekly fractionation schedule is a convenient and effective regimen and minimizes treatment visits for patients with ambulatory discomfort. A history of opportunistic infections appears to be a poor prognosticator of response to radiation treatments.

Adult↗

PubMed1999

Evaluation of the spatial accuracy of magnetic resonance imaging-based stereotactic target localization for gamma knife radiosurgery of functional disorders.

PURPOSE: This study was undertaken to determine the impact of geometric distortions on the spatial accuracy of magnetic resonance imaging (MRI)-guided stereotactic localization for gamma knife functional radiosurgery. METHOD: The spatial accuracy of MRI was evaluated by comparing stereotactic coordinates of intracranial targets, external fiducials, and anatomic structures defined by computed tomographic and MRI studies of the Radionics skull phantom (Radionics, Inc., Burlington, MA), the Rando head phantom, and 11 patients who underwent gamma knife functional radiosurgery. The distortion in MRI was assessed from computed tomographic and MRI fusion studies for these patients, as well as from MRI studies acquired by swapping the direction of the magnetic field gradients for five patients who underwent gamma knife radiosurgery and three patients who underwent MRI-guided frameless surgery. A follow-up program to compare the location of the created lesion with the intended target complemented the analysis. RESULTS: The average difference between computed tomographic and MRI stereotactic coordinates of external fiducials, intracranial targets, and anatomic landmarks was of the order of 1 pixel size (0.9 x 0.9 x 1 mm3) along the x, y, and z axes. The average linear scaling along these axes as determined by fusion studies was approximately 0.8% and consistent with a single pixel. The follow-up studies, available for seven patients, revealed good agreement between the location of the created lesion and the intended target. CONCLUSION: The spatial accuracy of an MRI-based localization system can be comparable to computed tomography-based localization with the added benefit of MRI resolution. Both machine- and object-related MRI distortions can be reduced to an acceptable level with contemporary scanners, optimized scanning sequences, and distortion-resistant stereotactic instruments.

Artifacts↗

PubMed1999

Apoptosis as a predictor of paclitaxel-induced radiosensitization in human tumor cell lines.

Paclitaxel is a deterpene with antitumor activity against a variety of human neoplasms. Paclitaxel cytotoxicity is thought to derive mainly from a stabilization of microtubules as a result of enhanced tubulin polymerization that leads to an accumulation of cells in the mitotic (M) phase of the cell cycle. Because cells in this phase of the cell cycle are known to be radiosensitive, it was thought that paclitaxel, in addition to its direct toxicity, may also sensitize tumor cell populations to radiation. Studies evaluating the radiosensitizing potential of paclitaxel in cultured cells have been equivocal, with only approximately 50% of the tested cell lines showing radiosensitization. To explain this variability, we advanced the hypothesis that the ability of paclitaxel to radiosensitize cells may be inversely correlated to the efficiency with which it induces apoptosis. To test this hypothesis, we studied paclitaxel-induced apoptosis and radiosensitization in seven human tumor cell lines. Approximately one-half of these cell lines showed radiosensitization that was associated with a low apoptotic index (<20% after a 48-h treatment with 10 or 20 nM paclitaxel). The results suggest that the level of apoptosis, after paclitaxel treatment, may predict for paclitaxel-induced radiosensitization, and that it could be introduced as a parameter for the optimization of combined treatment protocols.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Effect of higher radiation dose on biochemical control after radical prostatectomy for PT3N0 prostate cancer.

PURPOSE: The appropriate radiation dose has not been determined for postoperative radiation therapy (RT) of prostate cancer. Postoperative PSA level is a useful marker of local residual disease, and may allow evaluation of RT dose-response after radical prostatectomy. METHODS AND MATERIALS: Between 1989 and 1996, 86 consecutive patients with pT3N0 prostate cancer who did not receive prior hormonal therapy or chemotherapy were irradiated postoperatively. All patients received 55.8 to 70.2 Gy (median = 64.8 Gy) to the prostatic/seminal vesicle bed. Patients were judged to be free of biochemical failure (bNED) if their PSA remained undetectable or decreased to undetectable level (< 0.2 ng/ml). The median follow-up time was 32 months from time of irradiation. RESULTS: Univariate and multivariate analyses of variables showed that the preRT PSA level was the most significant predictor of improved bNED survival (p < 0.001). Actuarial analyses of radiation dose grouped with preRT PSA levels found higher radiation dose to be significant (p < 0.05). For the 52 patients with an undetectable preRT PSA level, the 3-year bNED rate was 91% for patients irradiated to 61.5 Gy or more and 57% for those irradiated to lower doses (p = 0.01). For the 21 patients with preRT PSA level > 0.2 and < or = 2.0 ng/ml, the 3-year bNED rate was 79% for patients irradiated to 64.8 Gy or more and 33% for those irradiated to a lower dose (p = 0.02). No other preRT PSA interval or radiation dose level was associated with a dose-response function. CONCLUSION: In patients with pT3N0 prostate cancer after radical prostatectomy, a radiation dose-response function may be present and depends on the preRT PSA value. Patients with high postoperative PSA levels (> 2.0 ng/ml) may be less likely to benefit from higher doses of RT, and should be considered a group for which systemic therapy should be tested.

Aged↗

PubMed1998

Is there a role for a brachytherapy vaginal cuff boost in the adjuvant management of patients with uterine-confined endometrial cancer?

PURPOSE/OBJECTIVE: Many patients who have uterine-confined endometrial cancer with prognostic factors predictive of recurrence are treated with adjuvant pelvic radiation. The addition of a brachytherapy vaginal cuff boost is controversial. MATERIALS AND METHODS: Between 1983 and 1993, 270 patients received adjuvant postoperative pelvic irradiation following hysterectomy for Stage I or II endometrial cancer. Group A includes 173 patients who received external beam irradiation alone (EBRT), while group B includes 97 patients who received EBRT with a vaginal brachytherapy application. The median dose of EBRT was 45 Gy. Vaginal brachytherapy consisted of a low dose rate ovoid or cylinder in 41 patients, a high dose rate cylinder in 54 patients, and a radioactive gold seed implant in two patients. The median follow-up time was 64 months. The two groups were compared in terms of age, histologic grade, favorable versus unfavorable histology, capillary space invasion, depth of myometrial invasion, and pathologic stage. RESULTS: Chi-square analysis revealed that the only difference between the two groups was the presence of more Stage II patients in group B (38% versus 14%). No difference was detected for 5 year pelvic control and disease-free survival rates between groups A and B. CONCLUSION: There is no suggestion that the addition of a vaginal cuff brachytherapy boost to pelvic radiation is beneficial for pelvic control or disease-free survival for patients with Stage I or II endometrial cancer. Prospective randomized trials designed to study external irradiation alone versus external beam treatment plus vaginal brachytherapy are unlikely to show a positive result. Because EBRT provides excellent pelvic control, protocol development for uterine-confined corpus cancer should focus on identifying patients at risk for recurrence as well as other means of augmenting EBRT (e.g. addition of chemotherapy) in order to improve disease free survival in those subgroups.

Adult↗

PubMed1998

Edema associated with I-125 or Pd-103 prostate brachytherapy and its impact on post-implant dosimetry: an analysis based on serial CT acquisition.

PURPOSE: To characterize the magnitude and duration of post-implant edema following the implantation of I-125 or Pd-103 seeds into the prostate and to investigate its effect on the CT-based calculation of the total dose delivered by the implant. MATERIALS AND METHODS: A pre-implant CT scan and 3 to 5 serial post-implant CT scans were obtained on 10 patients who received either I-125 or Pd-103 seed implants. None of the patients received hormone therapy. The magnitude and duration of edema were determined from the change in the spatial distribution of the implanted seeds as the edema resolves. Dose volume histograms were compiled to determine the percentage of the prostate volume that received a dose equal to, or greater than, the prescribed dose. RESULTS: The magnitude of the edema, expressed as the ratio of the post- to pre-implant volume on the day of the procedure, ranged from 1.33 to 1.96 (mean 1.52). The edema decreased exponentially with time; however, the edema half-life (time for the edema to decrease by 1/2) varied from 4 to 25 days (mean 9.3 days). As the edema resolved, the percentage of the prostate that received a dose equal to or greater than the prescribed dose increased by at least 7% in 7 of the 10 patients and increased by more than 15% in 2. In those patients in whom dose coverage was unaffected by the resolution of edema, more than 90% of the prostate was covered by the prescribed dose in the initial CT scan. CONCLUSION: Post-implant edema increased the prostate volume by factors which ranged from 1.33 to 1.96 (mean: 1.52). The edema resolved exponentially with an edema half-life which varied from 4 to 25 days (mean: 9.3 days). Edema had a significant effect on the post-implant dosimetry in 7 of 10 cases. Factors that affect the impact of edema on the dosimetry are the magnitude of the edema and the planned margin between the prescribed isodose line and the periphery of the prostate.

Brachytherapy↗

PubMed1998

Pathologic seminal vesicle invasion after radical prostatectomy for patients with prostate carcinoma: effect of early adjuvant radiation therapy on biochemical control.

BACKGROUND: The authors evaluated the effect of postoperative radiation therapy on freedom from biochemical failure (bNED) in men with prostate carcinoma who had pathologic seminal vesicle invasion after radical prostatectomy and negative pelvic lymph node dissection (pT3cN0). METHODS: Between 1989 and 1995, 375 men underwent radical prostatectomy at Thomas Jefferson University Hospital. Fifty-three men (13%) had pT3cN0 prostate carcinoma and were the subject of this analysis. Men in whom prostate specific antigen (PSA) could not be detected were deemed free of biochemical failure. RESULTS: Of the 53 men with pT3cN0 prostate carcinoma, 18 had an elevated PSA immediately after surgery and received salvage radiation therapy (RT). The 3-year bNED rate for this group was only 38%. At 3 months, PSA could not be detected in the other 35 men. Fifteen of those 35 men underwent early adjuvant RT, and the other 20 were observed for biochemical failure. The 3-year bNED rate for the 15 patients treated with immediate adjuvant RT was 86%, compared with 48% for the 20 men who were observed (P = 0.01). CONCLUSIONS: These data suggest that early adjuvant RT for men with pT3cN0 prostate carcinoma and no detectable PSA postoperatively reduces the likelihood of future biochemical failure. Men with pT3cN0 prostate carcinoma and a persistently elevated postoperative PSA level are less likely to benefit from RT and should be considered for systemic therapy.

Adenocarcinoma↗

PubMed1998

Adenocarcinoma of the fallopian tube: results of a multi-institutional retrospective analysis of 72 patients.

PURPOSE/OBJECTIVE: To determine the prognostic factors for predicting outcome of patients with adenocarcinoma of the fallopian tube and to evaluate the impact of treatment modalities in managing this uncommon disease. MATERIALS AND METHODS: A retrospective analysis of the tumor registries from 6 major medical centers from January 1, 1960 up to March 31, 1995 yielded 72 patients with primary adenocarcinoma of the fallopian tube. The Dodson modification of the FIGO surgical staging as it applies to carcinoma of the fallopian tube was utilized. Endpoints for outcome included overall and disease-free survival. Univariate analysis of host, tumor, and treatment factors was performed to determine prognostic significance, and patterns of failure were reviewed. RESULTS: The median age of the study cohort was 61 years (range 30-79 years). Stage distribution was 24 (33%) Stage I; 20 (28%) Stage II; 24 (33%) Stage III; and 4 (6%) Stage IV. Adjuvant chemotherapy was administered to 54 (75%) patients, and postoperative radiotherapy was employed in 22 (31%). In the latter treatment group, 14 (64%) had whole pelvic external beam irradiation, 5 (23%) whole abdominal radiotherapy, 2 (9%) P-32 instillation, and 1 (4%) vaginal brachytherapy alone. Chemotherapy was used in 67% of Stage I and in 79% of Stages II/III/IV disease (not significant); radiotherapy was more commonly employed in Stage I than in Stages II/III/IV (46% vs. 23%, p = 0.05). The 5-, 8-, 15-year overall and disease-free survival for the study patients were 44.7%, 23.8%, 18.8% and 27.3%, 17%, 14%, respectively. Significant prognostic factors of overall survival included Stage I vs. II/III/IV (p = 0.04) and age < or = 60 years vs. > 60 years at diagnosis (p = 0.03). Only Stage I vs. II/III/IV (p = 0.05) was predictive of disease-free survival. Patterns of failure included 18% pelvic, 36% upper abdominal, and 19% distant. For all patients, upper abdominal failures were more frequently found in Stages II/III/IV (29%) than in Stage I (7%) (p = 0.03). Relapses solely outside of what would be included in standard whole abdominal radiotherapy portals occurred for only 15% of patients (6 of 40) with failures. Furthermore, patients having any recurrence, including the upper abdomen, were more likely (p = 0.001) to die (45%) than those without any type of relapse (18%). CONCLUSION: This retrospective, multi-institutional study demonstrated the importance of FIGO stage in predicting the overall and disease-free survival of patients with carcinoma of the fallopian tube. Future investigations should consider exploring whole abdominal irradiation as adjunctive therapy, particularly in Stage II and higher.

Adenocarcinoma↗