Biomedical subjects

A M Markoe

Publications and source records attributed to A M Markoe.

At least 19 recordsLinked to original sources

PubMed1998

Does a radiation dose-response relation exist concerning survival of patients who have soft-tissue sarcomas of the extremities? Radiation dose-response relation for soft-tissue sarcomas.

This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.

Adolescent↗

PubMed1998

Bladder and rectal doses from external-beam boosts after gynecologic brachytherapy.

PURPOSE: To establish a typical value for radiation doses under pelvic midline shields. MATERIALS AND METHODS: Three methods were used to determine bladder and rectal doses under 5- or 6-half-value layer (HVL) shields for 10- and 24-MV external beams. First, dose was computed with a standard irregular field routine in 25 consecutive patients (aged 35-70 years) with stage IIB or IIIB disease treated with cesium-137 brachytherapy followed by a parametrial external-beam boost. Second, in vivo measurements with a solid-state probe were recorded during the first boost after completion of brachytherapy in each patient. Third, measurements obtained with an ionization chamber in a solid phantom (water-equivalent material) were compared with computed and in vivo results. RESULTS: All three dosimetric methods yielded bladder and rectal doses higher than the commonly assumed 5% of the unshielded primary beam dose. Doses within the shielded volume may be as high as 15% of the unshielded dose. Doses are similar under 5- and 6-HVL midline shields. Often, the actual bladder and rectal doses exceeded the planned dose limits and their corresponding maximum radiation dose tolerance levels. CONCLUSION: Bladder and rectal doses are higher than previously understood. Parametrial boosts may contribute as much as 3.0 Gy to the bladder and rectal doses.

Adult↗

PubMed1998

Gamma knife radiosurgery for large volume brain tumors: an analysis of acute and chronic toxicity.

Gamma Knife radiosurgery is often used to treat intracranial tumors <4 cm (approximately 13.5 cm3) in mean diameter. Larger lesions are rarely treated because of the expectation that increasing target volume will increase toxicity. We retrospectively analyzed 35 patients with primary or metastatic brain tumors of more than 13.5 cm3 treated with the Gamma Knife. Only 3 (8.5%) patients developed acute clinical toxicity. Nine (25%) patients developed post-Gamma Knife radionecrosis based on imaging studies, with only 3 of these patients (9% of the study population) having clinical progression of symptoms. Necrosis was not found to be related to prescribed dose, treatment volume or number of treated isocenters. We found no undue toxicity from the treatment of large brain tumors with the Gamma Knife.

Acute Disease↗

PubMed1997

Hyperfractionated radiation therapy and 5-fluorouracil, cisplatin, and mitomycin-C (+/- granulocyte-colony stimulating factor) in the treatment of patients with locally advanced head and neck carcinoma.

BACKGROUND: The authors had previously reported preliminary results of a treatment regimen of concurrent hyperfractionated radiation therapy and chemotherapy in patients with locally advanced head and neck carcinoma that demonstrated both feasibility and high local control. In an attempt to reduce acute mucosal and hematologic toxicity, granulocyte-colony stimulating factor (G-CSF) was added during the second phase of this study. METHODS: Seventy patients (53 with Stage IV and 17 with Stage III disease) were entered between May 1988 and June 1995 into a Phase I/II trial of concurrent radiation therapy (74.4 gray (Gy) total dose; 1.20 Gy twice daily), 5-fluorouracil (1000 mg/m2/24 hours for 72 hours), and cisplatin (50 mg/m2) for 3 cycles with the addition of mitomycin C (8 mg/m2) in Cycle 2. G-CSF was added after the initial entry of 34 patients. RESULTS: At a median follow-up of 41 months (range, 12-80 months), 44 patients were alive with a projected median overall survival of 54 months. Grade 3/4 mucositis, observed in 65% of patients, was equally prevalent and prolonged in both G-CSF-treated (+) and G-CSF-naive (-) patients. Grade 3/4 leukopenia was present in 45% and 36% of G-CSF- and G-CSF+ patients, respectively. The 3-year locoregional control and cause specific survival rates were 68% and 75%, respectively. CONCLUSIONS: This regimen was feasible and effective but caused severe mucositis. No benefit was derived from the addition of G-CSF. This regimen deserves further modification to reduce acute mucositis toxicity yet maintain the high locoregional control rate.

Adult↗

PubMed1997

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.

Antineoplastic Agents, Alkylating↗

PubMed1997

A quantitative assessment of standard vs. customized midline shield construction for invasive cervical carcinoma.

PURPOSE: An individualized midline shield (MLS) has been advocated for delivering homogeneous radiotherapy for patients with invasive cervical carcinoma. Yet, many radiation oncologists continue to employ a standard block. In the latter instance, any deviation of the cranial-caudal central axis of he tandem from the patient's midline could result in dose inhomogeneity to tumor. A retrospective review of a single university medical center's experience with constructing the MLS was initiated to determine the outcome of using a standard block vs. a customized block that conforms to the "Point A" isodose line. In addition, participating radiation oncologists associated with the Gynecologic Oncology Group (GOG) were polled to assess if there exists a consensus regarding midline block utilization in the management of cervical cancer patients which could be compared to the institutional study. METHODS AND MATERIALS: From January 1, 1990 through December 31, 1992, 32 patients with invasive cervical carcinoma who underwent low dose rate brachytherapy at a single institution were identified. Patients were grouped as having a standard block (18 cases), customized block (5 cases), or no block (9 cases). The "Point A" isodose distribution from the implant was superimposed onto the whole pelvic simulation film and quantitatively compared to the actual or a hypothetical standard block outlined on the same radiograph. In September of 1995, 56 member and affiliated institutions in the GOG were surveyed concerning their use of a MLS, and the results were tabulated in December of 1995. RESULTS: Approximately 72% of all cases (23 out of 32) at the single institution had tandem deviation ranging from 0-230 with a median of 50. This translated into a median percent overdosage to "Point A" Right of 15% and "Point A" Left of 12.5%. Although overall survival and incidence of chronic complications have not been affected by type of shielding, patient follow-up is limited with a median of 17.7 months (range: 4.2-58.9 months). Of the 56 surveyed radiation facilities in the GOG, 34 (61%) responded. One center was subsequently excluded as it performs only high dose rate brachytherapy. Of the evaluable respondents, 88% (29 out of 33) utilize a MLS in treating their patients with invasive cervical carcinoma. Of the latter group, 76% (22 out of 29), 21% (6 out of 29), and 3% (1 out of 29) employ a standard block, customized block, and a "step-wedge," respectively. For those using a standard block, 77% (17 out of 22) align the central cranial-caudal axis of the MLS along the corresponding midplane of the patient's pelvis on an anteroposterior radiograph rather than along the superior-inferior central axis of the tandem. CONCLUSIONS: This study suggests that the use of a standard midline shield could result in potential tumor dose inhomogeneity and should be avoided. A national survey of major academic centers further suggests that the majority of these facilities also utilize a rectangular central block that is not positioned with respect to possible tandem deviation. Further investigation concerning the techniques of midline shield construction should be considered.

Adult↗

PubMed1997

Modulation of cisPlatin cytotoxicity by interleukin-1 alpha and resident tumor macrophages.

The modulation of cisPlatin cytotoxicity by interleukin-1 (IL-1 alpha) was studied in cultures of SCC-7 tumor cells with and without tumor macrophages to examine potential mechanisms for the synergistic antitumor activity of cisPlatin and IL-1 alpha in SCC-7 solid tumors. Neither IL-1 alpha nor tumor macrophages affected the survival of clonogenic tumor cells and IL-1 alpha had no direct effect on tumor cell growth in vitro. Macrophages had no direct effect on cisPlatin sensitivity (IC90 = 6.0 microM), but, the addition of IL-1 alpha (500-2000U/ml) to co-cultures of cisPlatin pretreated tumor cells and resident tumor macrophages increased cell killing (IC90 = 3.1 microM). Similar responses were seen in primary cultures treated with cisPlatin before IL-1 alpha. The modulation of cisPlatin cytotoxicity by IL-1 alpha exhibited a biphasic dose response that paralleled the IL-1 alpha dose dependent release of H2O2 by resident tumor macrophages. Further, IL-1 alpha modification of cisPlatin cytotoxicity was prompt and inhibited by catalase. CisPlatin and exogenous H2O2 (50 microM) produced more than additive SCC-7 clonogenic cell kill and hydroxyl radicals played an important role in the response. Interleukin-1 modulation of cisPlatin cytotoxicity was schedule dependent. IL-1 alpha treatment for 24 hrs, before cisPlatin, produced drug resistance (IC90 = 11.1 microM). Our study shows that IL-1 alpha can stimulate tumor macrophages to release pro-oxidants that modify cellular chemosensitivity in a schedule and dose dependent fashion. Our findings may also provide a mechanistic explantation for the synergistic antitumor activity of cisPlatin and IL-1 alpha in vivo.

Animals↗

PubMed1997

The role of hyperfractionated re-irradiation in metastatic brain disease: a single institutional trial.

Progression of brain metastases after brain irradiation has prompted several studies on retreatment of the brain. Increased durations of survival and improved quality of life have been reported. Fifteen patients with previously treated brain metastases were entered into this pilot study between May 1990 and January 1994. All patients had neurologic and/or radiologic evidence of progression of brain metastases. The lung was the primary site in 60% of cases. The remaining 40% had breast, ovarian, and skin primaries. The median interval between the first treatment and retreatment was 10 months. All patients received whole-brain irradiation with or without a boost for their initial treatment course. Doses ranged from 3,000 to 5,500 cGy for initial treatments (median, 3,000). Retreatment consisted of limited fields with a median side equivalent square of 8.8 cm. Patients were retreated with a median dose of 3,000 cGy (range, 600-3,000 cGy). A median cumulative dose of 6,000 cGy was achieved. Retreatment consisted of twice-daily fractions (150 cGy/fraction). Retreatment was tolerated without serious complications. Of the 15 patients treated, nine (60%) experienced improvement, and five (27%) had stabilization of neurologic function and/or radiographic parameters. Median survival was 3.2 months; two of the reirradiated patients survived > or = 9 months. In conclusion, reirradiation is a viable option in patients with recurrent metastatic lesions of the brain, and the use of a limited retreatment volume makes this a well-tolerated, low-morbidity treatment that leads to clinical benefits and, in some instances, enhanced survival. The influence of hyperfractionation on the outcome needs to be investigated further in large series.

Adult↗

PubMed1996

External beam radiation for retinoblastoma: results, patterns of failure, and a proposal for treatment guidelines.

PURPOSE: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. METHODS AND MATERIALS: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. RESULTS: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). CONCLUSIONS: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control in retinoblastoma eyes Groups I-II (Reese-Ellsworth classification) or tumors measuring 15 mm in diameter or less. Eyes in more advanced group staging or containing tumors larger than the 15 mm seem to require higher radiation doses. We propose treatment guidelines for external beam radiation of retinoblastoma that specifically take into account the important clinical variables of tumor stage and patient age. 2) External beam radiation does not prevent the appearance of new tumors in clinically uninvolved retina. Therefore, the traditional belief that external beam radiation can treat the retina "prophylactically" should be seriously questioned. Due to this finding and their significant less morbidity, focal treatment modalities (plaque brachytherapy, photocoagulation, and/or cryotherapy), when clinically feasible, should be considered the treatment of choice for intraocular retinoblastoma. External beam radiation should be considered only when focal treatment modalities are not clinically indicated.

Dose-Response Relationship, Radiation↗

PubMed1996

Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. OBJECTIVE: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. METHODS: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48 degrees C or 54 degrees C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48 degrees C or 54 degrees C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. RESULTS: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 degrees C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48 degrees C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54 degrees C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. CONCLUSIONS: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control.

Animals↗

PubMed1996

Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy in the treatment of retinoblastoma may decrease treatment-related morbidity and second tumor-associated mortality, while maintaining excellent tumor control rates. OBJECTIVE: To evaluate tumor control and potential synergy between intravitreally delivered carboplatin and external beam radiation therapy (EBRT), using a transgenic murine model of spontaneous heritable retinoblastoma. METHODS: Sixty-six mouse eyes from 4-week-old transgenic mice positive for the simian virus 40 large T antigen were evaluated. Thirty-three mice were treated with 5 intravitreal injections of carboplatin (ranging from 0.1-4.0 micrograms) combined with concurrent bilateral EBRT (ranging from 10-30 Gy) delivered in twice daily 5-Gy fractions. All eyes were followed up for treatment complications. Twelve weeks following final treatment, all eyes were enucleated, serial histologic sections obtained, and the eyes examined for the presence of retinoblastoma. RESULTS: No eye treated with 0.1 microgram of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 microgram of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 microgram of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 micrograms of carboplatin in combination with EBRT had complete tumor control. The chemotherapeutic enhancement ratio ranged from 1.07 to 3.24. CONCLUSIONS: Combined administration of intravitreal carboplatin and EBRT enhances local tumor control in murine retinoblastoma. Combining these treatment modalities may allow tumor control in selected patients with retinoblastoma while decreasing treatment-related morbidity and the mutagenic risks associated with radiation and systemic chemotherapy.

Animals↗

PubMed1996

Management of stage I-B, II-A, and II-B carcinoma of the cervix with high-dose-rate brachytherapy: initial results of an institutional clinical trial.

In 1989, the University of Miami began a program incorporating high-dose-rate (HDR) brachytherapy into the definitive treatment of patients with invasive carcinoma of the cervix. Patients received an average total dose to point A of 5,511 cGy (range 4,280-6,360 cGy) in an average of 57 days (range 39-84 days). An analysis of the first 24 cases found 11 FIGO Stage I-B, four Stage II-A, and nine Stage II-B tumors. At the end of all radiation therapy, 19/24 patients' tumors (79.2%) had undergone a clinical complete response (CR). With median follow-up of 26 months (range 14-63 months), three have relapsed locally, two regionally, and six in extrapelvic sites. Almost two-thirds of all failures occurred in patients with tumors >4 cm, who also took more than 8 weeks to complete their treatment. Overall 2-year actuarial survival for the entire study group is approximately 74%. A univariate analysis determined that clinical stage (P = 0.02), overall treatment time (P = 0.03), tumor size (P = 0.05), and response at the end of therapy (P = 0.005) were significant prognostic factors. Multivariate analysis showed that tumor response to therapy was the most important prognosticator of outcome (P = 0.001). Besides five cases of apical vaginal stenosis, there have been no reported chronic complications in this cohort of patients. A prospectively randomized trial is recommended to compare the efficacy of HDR vs. low-dose-rate brachytherapy in cervical carcinoma.

Adenocarcinoma↗

PubMed1996

Intraoperative echographic localization of iodine 125 episcleral radioactive plaques for posterior uveal melanoma.

PURPOSE: Plaque radiotherapy has been reported to have a higher relapse rate than charged-particle radiotherapy for posteriorly located uveal melanomas, which also are more technically difficult to localize accurately. The authors used intraoperative echography in patients with posterior uveal melanoma to determine the rate of inaccurate localization of iodine 125(125I) episcleral plaques using standard localization techniques. METHODS: The authors reviewed the records of 29 consecutive patients with medium-sized posterior uveal melanomas who underwent 125I episcleral plaque radiotherapy with intraoperative echographic verification of plaque placement. RESULTS: After careful plaque placement using standard localization techniques, 4 of 29 plaques (14%) did not cover at least one tumor margin. All four of these plaques were associated with posterior tumors with at least one margin posterior to the temporal arcades. Two (7%) additional juxtapapillary plaques were displaced away from the sclera by the optic nerve. In all six cases, it was possible to immediately reposition the plaque to achieve coverage of all tumor margins. CONCLUSIONS: Placement of 125I episcleral radioactive plaques for posteriorly located uveal melanomas using standard localization techniques occasionally results in suboptimal plaque positioning. Intraoperative echography can identify plaques that are localized poorly and allows immediate adjustment to achieve optimal plaque positioning.

Brachytherapy↗

PubMed1996

Stereotactic dose computation and plan optimization using the convolution theorem. I. Dose computation.

With Leksell Gamma Knife stereotactic radiosurgery, the dose distribution delivered by a specific helmet can be assumed to remain as a fixed-dose distribution when the shot is moved to different locations within the predefined dose calculation matrix. The convolution theorem may be implemented to take advantage of this fact for fast dose computation and plan construction. Using this technique, the shot spatial arrangement is formulated as a convolution kernel, which is theoretically a three-dimensional multi-delta function. The dose distribution is computed by the convolution of this single-shot dose distribution with the shot convolution kernel. To determine the shot arrangement, an ideal dose distribution is generated based upon the target structure. Deconvolution is then applied to find the convolution kernel which best fits the proposed ideal dose distribution. The primary task of this presentation is to focus on and describe in detail the dose computation using the convolution theorem.

Algorithms↗

PubMed1996

Radioresistance in murine solid tumors induced by interleukin-1.

Interleukin-1 (IL-1) has radioprotective activity in hematopoietic lineages and in other normal cell renewal systems, but little is known about the effects of IL-1 alpha on the radiosensitivity of tumor cell populations. The present studies were conducted to investigate the effects of IL-1 alpha on the radiosensitivity of clonogenic cells in RIF-1 and SCC-7 tumors. Radioresistance was detected within 2-4 after administration of IL-1 alpha (0.5 micrograms/mouse, ip) and characterized by increases in D(o), Dq, alpha/beta and SF2. This radioresistance was similar to that seen in tumors rendered totally hypoxic before X irradiation. Tirapazamine, a hypoxic cell cytotoxin, and IL-1 alpha had synergistic schedule-dependent antitumor activity in vivo, suggesting that IL-1-induced radioresistance in vivo is due to hypoxia. Radioresistance induced by IL-1 alpha was transient, and the data suggested reoxygenation within 12 h. In vitro, IL-1 alpha had no direct effect on the radiosensitivity of SCC-7 cells in tissue culture under aerobic conditions. However, an increase in D(o), alpha/beta and SF2 was seen in clonogenic tumor cells from primary cultures treated with IL-1 alpha under aerobic conditions. Superoxide dismutase and catalase prevented the induction of radioresistance by IL-1 alpha in vitro, suggesting that oxidative responses from tumor macrophages after administration of IL-1 alpha may be responsible for induced radioresistance by IL-1 in vitro. Although oxidant stress induced by IL-1 and in vitro in our models, the mechanisms by which such responses modulate tumor radiosensitivity in vivo and in vitro are likely quite different.

Animals↗

PubMed1994

A multivariate analysis of clinicopathologic factors for predicting outcome in uterine sarcomas.

This study involved a comprehensive review of the histologic slides of 62 patients who were diagnosed with uterine sarcoma from 1978 through 1988 at a single institution. In addition, DNA content (ploidy level) could be determined from the H & E slides of these tumors using image analysis. Also, 42 of these cases had retrievable cell blocks on which DNA analysis was performed by means of flow cytometry. A linear regression analysis found a high degree of correlation (r = 0.8) between the measurement of the DNA index of these tumors by these two techniques. All cases were retrospectively restaged using the newly adopted FIGO surgical staging criteria which found the following distribution: 22 (35.5%) Stage I, 10 (16.1%) Stage II, 12 (19.4%) Stage III, and 18 (29%) Stage IV. A multivariate analysis of 60 evaluable patients using the Cox proportional hazard model found that surgical staging was the most significant prognostic factor with respect to the endpoint of overall survival (P = 0.00004). Both patient age at diagnosis and mitotic index were independent from surgical staging in predicting outcome. Furthermore, there was a trend suggesting that DNA index also had prognostic value. Of particular interest was that patients with diploid tumors (DNA index, 0.9-1.1) had a 5-year overall survival of 72% and did not approach median survival; however, hyperdiploid tumors (DNA index > 1.1) and hypodiploid tumors (DNA index < 0.9) were associated with median survivals of 18 and 12 months, respectively. In conclusion, this study supports the use of surgical staging of patients with uterine sarcomas in order to optimally determine their chance for survival. Further biologic investigations which may result in identifying those patients who could benefit from adjunctive treatment are recommended.

Adult↗

PubMed1994

Long-term follow-up of gliomas treated with fractionated stereotactic irradiation.

Eighteen patients have been treated for gliomas with fractionated stereotactic linear accelerator (LINAC) irradiation. A plastic halo ring secured with skull pins allows daily attachment of the patient to the stereotactic frame mounted on the linear accelerator. The patients received 9-31 fractions of 1.8-3 Gy/fraction over periods of 20-49 days. Total doses delivered stereotactically where 16-60 Gy (90% isodose) delivered to 3-7 cm diameter tumors. The six patients with glioblastoma had a median survival of 16 months (range 7-60 months). The two patients with anaplastic astrocytoma survived 7 and 78 months. Most of the patients with high grade tumors also received other adjuant treatments. Of the ten patients with low grade gliomas, one expired 66 months after treatment, and the remainder are alive 22-82 months after treatment. One pediatric patient displayed evidence of focal radiation injury with visual loss. No patient developed initial recurrence of tumor outside the focally irradiated field. Stereotactic localization of irradiation protects surrounding brain tissue; fractionation improves the therapeutic ratio. These extended follow-up data indicate that stereotactic restriction of radiation fields in treatment of gliomas does not result in deterioration of survival results. Further investigation is warranted into the use of higher focal fractionated radiation doses to attempt to improve local control and survival.

Adolescent↗

PubMed1994

Neurologic complications of Merkel cell carcinoma.

We describe a 61-year-old man with a multiple neurologic complication of Merkel cell carcinoma, a rare skin cancer. An enhancing brain mass, and cytologically proven leptomeningeal disease produced a succession of symptoms including seizures, bilateral radiculopathies, myoclonus, a cauda equina syndrome and altered mental status. Aggressive treatment prolonged his survival marginally.

Antineoplastic Combined Chemotherapy Protocols↗