Comment on "survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, Phase I-II Study".
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Glioblastoma↗
Biomedical subjects
T L Phillips
Publications and source records attributed to T L Phillips.
A Carboniferous insect gall: insight into early ecologic history of the Holometabola.
Although the prevalence or even occurrence of insect herbivory during the Late Carboniferous (Pennsylvanian) has been questioned, we present the earliest-known ecologic evidence showing that by Late Pennsylvanian times (302 million years ago) a larva of the Holometabola was galling the internal tissue of Psaronius tree-fern fronds. Several diagnostic cellular and histological features of these petiole galls have been preserved in exquisite detail, including an excavated axial lumen filled with fecal pellets and comminuted frass, plant-produced response tissue surrounding the lumen, and specificity by the larval herbivore for a particular host species and tissue type. Whereas most suggestions over-whelmingly support the evolution of such intimate and reciprocal plant-insect interactions 175 million years later, we provide documentation that before the demise of Pennsylvanian age coal-swamp forests, a highly stereotyped life cycle was already established between an insect that was consuming internal plant tissue and a vascular plant host responding to that herbivory. This and related discoveries of insect herbivore consumption of Psaronius tissues indicate that modern-style herbivores were established in Late Pennsylvanian coal-swamp forests.
Journal Article↗
Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme.
PURPOSE: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I implant boost after external beam radiotherapy. METHODS AND MATERIALS: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analysis of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. RESULTS: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm3 of normal brain. CONCLUSION: Although higher minimum tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy boost dose of 45-50 Gy in conjunction with conventional external beam radiotherapy, and reoperation for symptomatic necrosis.
Adolescent↗
Long-term follow-up after high-activity 125I brachytherapy for pediatric brain tumors.
A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.
Adolescent↗
Radiotherapy for high grade clinically localized adenocarcinoma of the prostate.
PURPOSE: We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy. RESULTS: Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46% of the cases and stage T3 or T4 in 54%. The overall actuarial probability of freedom from biochemical failure at 4 years was 23%. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64% free of progression if the pretreatment PSA was 10 ng./ml. or less compared to only 16% at 3 years if PSA was more than 10 ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA less than 20 ng./ml. 83% of those treated to more than 71 Gy. were free of progression compared to 0% for those treated to less than 71 Gy. (p = 0.03). In a multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy. (relative risk 4.0, p = 0.06) were associated with a favorable outcome. CONCLUSIONS: At 4 years the freedom from PSA failure following radiotherapy for high grade prostate cancer was comparable to previously reported surgical series. The high failure rate among patients with PSA greater than 20 ng./ml. suggests that these patients should be considered for investigational approaches. The apparent improvement in freedom from progression with the use of higher doses provides reason for optimism.
Actuarial Analysis↗
Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89-05.
PURPOSE: To determine if the addition of bromodeoxyuridine (BrdUrd) to radiotherapy prolongs survival when compared to radiotherapy alone in patients with brain metastases. METHODS AND MATERIALS: Seventy-two patients with brain metastases were randomized to 37.5 Gy in 15 fractions of 2.5 Gy or to the same dose with BrdUrd 0.8 g/m2 per day for 4 days of each of 3 weeks. Drug treatment was begun on Thursday or Friday before the first week of radiotherapy. Patients had a Karnofsky performance score of at least 70, a neurological function classification of 1 or 2, and any primary tumor except central nervous system (CNS), leukemia, or lymphoma. The primary was absent, controlled, or under active radiotherapy. Patients were free of other metastases. They were stratified by primary site (breast, lung or other), number of metastases (single or multiple) and age (< 60 vs. > 60). RESULTS: There was no significant difference between the two treatment arms (p = 0.904). The study was open from October 1989 to March 1993 and accrued 72 patients. Only one patient in the RT only arm remains alive. The two treatment arms were balanced with respect to all stratification variables. Toxicity due to radiotherapy was similar in both arms. BrdUrd caused significant Grade 4 and 5 hematologic and skin toxicity in five patients. Two patients died due to hematologic toxicity and one from a Stevens-Johnson type skin reaction. Phenytoin played a role in the skin reactions and ranitidine was associated with the hematologic deaths. Ranitidine was eliminated, BrdUrd was discontinued after any hematologic toxicity, and no further Grade 4 or 5 toxicities were seen. The median survival was 6.12 months in the radiotherapy group and 4.3 in the BrdUrd group (p = 0.904). Patients with solitary brain metastases had significantly better survival (p = 0.031). CONCLUSIONS: BrdUrd did not enhance the efficacy of the radiotherapy regimen tested, in spite of the fact that brain metastases have shown high labeling indices. The toxicity of this schedule of BrdUrd administration was apparently increased by ranitidine and phenytoin.
Adult↗
Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas.
PURPOSE: To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. METHODS AND MATERIALS: Between 1983 and 1987, study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday, to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. RESULTS: One-hundred thirty eight patients (median age, 43 years) were evaluable for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum (n = 116) is 46%. For the astrocytoma (ASTRO) stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate (p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age (p < 0.001), Karnofsky performance score (p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade > or = III leukopenia in 18%, and Grade > or = III thrombocytopeni in 9%. CONCLUSION: The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.
Adolescent↗
The value of nonuniform margins for six-field conformal irradiation of localized prostate cancer.
PURPOSE: Evaluate the hypothesis that by combining nonuniform margins with a technique for limiting the possible extent of posterior motion of the prostate during the delivery of six-field conformal radiotherapy (SFCRT) of the prostate, it is possible to adequately treat the clinical target volume (CTV) and minimize dose to normal structures. METHODS AND MATERIALS: Serial computed tomography (CT) scans of prostate patients were taken at 0.5 cm intervals for treatment planning purposes. The initial treatment planning scans were performed with the rectum empty and the bladder full. Subsequent scans were taken at the end of the first week of treatment with the bladder full, but with no attempt to empty the rectum, to mimic the typical treatment situation. The gross tumor volume (GTV), consisting of the prostate and seminal vesicles, as well as the CTV, were defined on the CT images with the aid of a urethrogram to define the inferior border (apex) of the prostate. Variable blocking margins were designed around the CTV using the University of Michigan three dimensional (3D) treatment planning system (UM-PLAN). Isodose distributions displayed on axial, sagittal, coronal, and oblique slices were used to evaluate the adequacy of the various margins applied. Nonuniform margins varying from 0.75 cm posteriorly to 2.0 cm anteriorly and inferiorly were compared to uniform margins of 1.0, 1.5, and 2.0 cm for each patient. Dose volume histograms (DVH) were used to compare doses to the GTV, CTV, rectum, and bladder. RESULTS: In a series of 10 patients scanned with the above protocol, treatment plans with nonuniform margins were compared with uniform margins of 1.0, 1.5, and 2.0 cm. Dose-volume histograms showed that nonuniform and 1.0 cm uniform margins deliver the lowest doses to the rectum and bladder, but the use of 1.0 cm uniform margins resulted in inadequate coverage of the CTV in 40% of the cases. The 1.5 and 2.0 cm uniform margins adequately covered the CTV but resulted in significantly higher doses to the bladder and rectum. CONCLUSIONS: The use of nonuniform margins, when combined with CT scans performed with the rectum empty and bladder full, can improve tumor control probability while minimizing the risk of morbidity to adjacent critical structures.
Humans↗
Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems.
Toxicity of the respiratory system is a common side effect and complication of anticancer therapy that can result in significant morbidity. The range of respiratory compromise can extend from acute lethal events to degrees of chronic pulmonary decompensation, manifesting years after the initial cancer therapy. This review examines the anatomic-histologic background of the lung and the normal functional anatomic unit. The pathophysiology of radiation and chemotherapy induced lung injury is discussed as well as the associated clinical syndromes. Radiation tolerance doses and volumes are assessed in addition to chemotherapy tolerance and risk factors and radiation-chemotherapy interactions. There are a variety of measurable endpoints for detection and screening. Because of the wide range of available quantitative tests, it would seem that the measurement of impaired lung function is possible. The development of staging systems for acute and late toxicity is discussed and a new staging system for Late Effects in Normal Tissues (LENT) is proposed.
Clinical Protocols↗
RTOG Late Effects Working Group. Overview. Late Effects of Normal Tissues (LENT) scoring system.
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Humans↗
EORTC Late Effects Working Group. Overview of late effects normal tissues (LENT) scoring system.
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Diagnostic Imaging↗
3D conformal radiotherapy in the sagittal plane for centrally located thoracic tumors.
One hundred patients, recently treated at the University of California, San Francisco (UCSF) with radiotherapy for lung and esophageal cancer, were studied. Three subsets of these patients were defined based on tumor location to test how commonly the use of three-dimensional (3D) conformal radiotherapy (3DCRT) could improve significantly the delivery of high dosages. Comparisons were made between isodose distributions and dose volume histograms (DVHs) of patients' prior computed tomography (CT)-based treatment plans and newly generated 3D-based treatment plans. The use of beam angles outside the conventional horizontal plane did not significantly improve the dose distribution for patients if a peripheral mass was the target volume. Patients with a target volume involving the central thorax represented a subset (> 40% of the patients) who would have benefited the most from the use of nonconventional beam angles. In these patients, sagittal coplanar beams (sagittal Y technique) reduced the dose to 30% of the lung volume from 30% to 5%. Doses to the spinal cord and heart were slightly higher than with conventional techniques but were within the tolerance of normal tissues. The sagittal Y technique allows an escalation in total dose to the tumor without increasing dose to normal tissues beyond their tolerance.
Esophageal Neoplasms↗
Applications of asymmetric collimation on linear accelerators.
Frequency of use of asymmetric collimation (AC) at an academic radiation oncology center equipped with AC-capable linear accelerators was determined, and the type of use was cataloged. Records of patients beginning radiation treatment at U.C. Davis Cancer Center within a 3-month period (3/1/92 to 5/31/92) were reviewed. Forty-seven percent of 102 patients and 56% of 123 courses of treatment involved AC. Six common uses of AC were identified: beam-split field matching, planned boosts, other field size changes, adjustments to match divergent fields, matchline feathering, and opposed tangential fields. This study demonstrates that asymmetric collimation is a useful and powerful clinical treatment tool with widespread applications to radiation therapy.
Cohort Studies↗
Radiation-induced decrease in nitric oxide synthase--containing nerves in the rat penis.
PURPOSE: Evaluate effect of prostatic irradiation on erectile function. MATERIALS AND METHODS: Forty-seven male adult rats were divided into three groups according to a single radiation dose to the prostate: control (no irradiation) (n = 15), 1,000 cGy (n = 15), and 2,000 cGy (n = 17). Five months after irradiation, rats underwent evaluation of penile vascularity and of erectile response to central and peripheral stimulation. After the study a proximal-shaft penile segment was obtained for staining. RESULTS: Histologic evaluation demonstrated that, with increasing radiation, the number of nitric oxide synthase-containing nerve fibers per penile segment decreased significantly: control, 225.6 +/- 9.7; 1,000 cGy, 156.3 +/- 12.0; 2,000 cGy, 85.8 +/- 10.1 (standard error of the mean). Maximal intracavernous pressure induced with electrostimulation decreased significantly with increasing radiation dose. After injection of papaverine, maximal intracavernous pressure was significantly decreased in only the 2,000-cGy group. CONCLUSION: A dose of 2,000 cGy over the prostatic bed induces erectile dysfunction by causing defects in the vascular supply of the erectile tissue and in the nerves and smooth muscle.
Amino Acid Oxidoreductases↗
Radiation pneumonitis following combined modality therapy for lung cancer: analysis of prognostic factors.
PURPOSE: To identify factors associated with radiation pneumonitis (RP) resulting from combined modality therapy (CMT) for lung cancer. MATERIALS AND METHODS: Series published before 1994 that used CMT for the treatment of lung cancer and explicitly reported the incidence of RP are the basis for this analysis. Factors evaluated included the radiation dose per fraction (Fx), total radiation dose, fractionation scheme (split v continuous), type of chemotherapy and intended dose-intensity, overall treatment time, histology (small-cell lung cancer [SCLC] v non-small-cell lung cancer [NSCLC]), and treatment schedule (concurrent v induction, sequential, or alternating CMT). RESULTS: Twenty-four series, including 27 treatment groups and 1,911 assessable patients, met our criteria for inclusion in this analysis. The median total dose of radiation used in the trials analyzed was 50 Gy (range, 25 to 63 Gy). The median daily Fx used was 2.0 Gy (range, 1.5 to 4.0 Gy). Nineteen series included 22 treatment groups and 1,745 patients treated with single daily fractions. Among these patients, 136 received a daily Fx greater than 2.67 Gy. Five series used twice-daily radiotherapy and included 166 patients (Fx, 1.5 to 1.7 Gy). The incidence of RP was 7.8%. In a multivariate analysis, only daily Fx, number of daily fractions, and total dose were associated with the risk of RP (P < .0001, P < .018, and P < .003, respectively). CONCLUSION: In this analysis, the use of Fx greater than 2.67 Gy was the most significant factor associated with an increased risk of RP. High total dose also appears to be associated with an increased risk, but twice-daily irradiation seems to reduce the risk expected if the same total daily dose is given as a single fraction. High-Fx radiotherapy should be avoided in patients who receive CMT with curative intent.
Antineoplastic Combined Chemotherapy Protocols↗
Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost.
A retrospective review was undertaken to study the influence of age on the survival of patients undergoing brachytherapy boost for glioblastoma multiforme. From February 1981 through December 1992, 159 adults with primary glioblastoma multiforme underwent high-activity iodine-125 brain implant boost after external beam radiotherapy. There were 98 men and 61 women, ranging in age from 18 to 73 years (median, 52 yr). Karnofsky performance scores ranged from 70 to 100 (median, 90). Surgery before radiotherapy consisted of biopsy in 7% of patients, subtotal resection in 66%, and gross total resection in 27%. External beam radiotherapy doses ranged from 39.6 to 76.8 Gy, with 91% of patients receiving 59.4 to 61.2 Gy. Brachytherapy doses ranged from 35.7 to 66.5 Gy (median, 55.0 Gy) at 0.30 to 0.70 Gy per hour (median, 0.43 Gy/h). Reoperations were performed in 81 patients (51%). Information on quality of life was available for 13 of the 14 living 3-year survivors; 10 patients were steroid independent, and mean Karnofsky performance scores had decreased from 92 at the time of brachytherapy to 75 at the last follow-up. Univariate and multivariate analyses showed that age was the most important parameter influencing survival (P < 0.0005). The nine patients 18 to 29.9 years old had a 3-year survival probability of 78 +/- 14% (median survival was not yet reached at the time of this report), with a follow-up of 145 to 511 weeks in living patients (median, 322 wk).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Genotypic analysis of Epstein-Barr virus isolates associated with nasopharyngeal carcinoma in Chinese immigrants to the United States.
EBV genotypes of first- and second-generation Chinese diagnosed with nasopharyngeal carcinoma in the United States were analyzed by PCR techniques. Previous studies showed a geographical distribution of genotypically distinct sub-types of EBV. Viruses detected at a higher frequency among Chinese NPC patients (Cf) were distinguished from those found in the majority of Caucasian NPC patients (DF) in the United States by polymorphisms in the BamHI F and I regions. Exploiting this distinction, we analyzed the biopsies of Chinese immigrants in the United States for their C/D and F/f genotypes to evaluate the importance of retention of the Cf virus among Chinese NPC patients in a geographical area where the DF virus prevails. This study shows that approximately 45.5 to 50% of first- and second-generation Chinese NPC patients in California harbor the Cf virus, which is present in only 8% of Caucasian NPC patients in California. It is interesting that, while only 48% of the viral isolates from immigrant Chinese to California harbor the "f" variant, 96% harbor the type-C viruses.
Base Sequence↗
Experience in charged particle irradiation of tumors of the skull base: 1977-1992.
PURPOSE: To review the experience at University of California Lawrence Berkeley Laboratory in using charged particles to irradiate primary neoplasms of the skull base and those extending to the skull base from the nasopharynx and paranasal sinuses. METHODS AND MATERIALS: During the period from 1977 to 1992, 223 patients were irradiated with charged particles at the Lawrence Berkeley Laboratory for tumors either arising in or extending to the skull base, of whom 48 (22%) had recurrent lesions, either post previous surgery or radiotherapy. One hundred twenty-six patients had lesions arising in the cranial base, mostly chordoma (53), chondrosarcoma (27), paraclival meningioma (27) with 19 patients having other histologies such as osteosarcoma or neurofibrosarcoma. There were also 31 patients with primary or recurrent squamous carcinoma of the nasopharynx extending to the skull base, 44 patients with major or minor salivary gland tumors, mostly adenocarcinoma, and 22 patients with squamous carcinoma of the paranasal sinuses, all with cranial base extension. RESULTS: Local control and survival appeared improved in tumors arising in the skull base, following the ability with charged particles to deliver high doses (mean of 65 Gy-equivalent) with relative sparing of the adjacent normal tissues. The Kaplan-Meier 5-year local control was 85% for meningioma, 78% for chondrosarcoma, 63% for chordoma and 58% for other sarcoma. Follow-up ranged from 4-191 months with a median of 51 months. CONCLUSION: Charged particle radiotherapy is highly effective in controlling cranial base lesions which have have been partially resected. Better tumor localization with CT and MRI, improved 3-D treatment planning and beam delivery techniques have continued to reduce the level of serious complications and increase local control and survival.
Female↗