Radiation Therapy Oncology Group. Research Plan 2002-2006. Breast Cancer Working Group.
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Biomedical subjects
Publications and source records attributed to P S Craighead.
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PURPOSE: This is a Phase I/II dose escalation study to determine the tolerable dose of tirapazamine (TPZ), and the toxicity of a regimen using TPZ with cisplatin, and radiotherapy in women with locally advanced cervical cancer. METHODS AND MATERIALS: Eligible women for this study were those with a diagnosis of locally advanced cervix cancer, who were less than 75 years of age, having provided informed consent, and who had undergone the necessary prestudy investigations. External-beam radiotherapy (RT) was given to a minimum dose of 4500 cGy in 25 fractions (Day 1-35), and brachytherapy then delivered to bring the total dose at point A to 8500 cGy. The first dose level of the study used TPZ 190 mg/m(2) and cisplatin 75 mg/m(2) on Days 1, 15, and 29 of RT. TPZ 160 mg/m(2) alone was used on Days 8, 10, 12 and 22, 24, 26 of RT. A conventional dose-escalation step method was then used to determine the maximum tolerated dose (MTD) of TPZ. RESULTS: Four patients were treated at Level 1, 6 at Level 2, and 5 at Level 3. Only 1 patient experienced a dose-limiting toxicity (DLT) at Level 2, but 2 of the 5 patients at Level 3 incurred DLTs. Level 2 was declared the MDT (TPZ 290 mg/m(2) on Days 1, 15, 29 and 220 mg/m(2) on Days 8, 10, 12 and 22, 24, 26). At 6 months, 13 of 15 patients had complete pelvic control of disease. CONCLUSION: Level 2 of this regime was identified as the MDT. The use of TPZ with concurrent cisplatin and pelvic radiotherapy has acceptable toxicity and should be considered for further Phase 2 testing in view of the promising responses noted.
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OBJECTIVE: The aim of this study was to determine the patient characteristics and outcome of patients with aggressive histologic variants (AV) of endometrial carcinoma, including uterine papillary serous carcinoma (UPSC), uterine clear cell carcinoma (UCCC), and mixed type. METHODS AND MATERIALS: All cases with AV histological type of endometrial carcinoma from January 1984 to December 1994 at the Tom Baker Cancer Centre were identified using the Alberta Cancer Registry. Relevant data from the charts of these patients were entered into a study database (Microsoft Excel) and analyzed for presentation, demography, treatment parameters, and outcome of treatment. All pathology was reviewed at the time of diagnosis. Statistical analysis was performed using the S-plus statistics computer program. Univariate and multivariate analyses were used to assess independent prognostic factors using the Cox proportional hazards model. RESULTS: A total of 103 patients with AV histological type were identified and analyzed; there were 61, 31, and 11 cases of UPSC, CCC, and mixed tumors, respectively. Sixty-three patients had Stage I, 11 had Stage II, 15 had Stage III, and 14 had Stage IV disease. The median age of patients was 67 years with a range of 36 to 86 years. Median follow-up was 60 months with a range of 36 to 156 months. The Cox proportional hazards model showed that lymphvascular space invasion and stage are the two independent prognostic factors affecting recurrence and survival. Forty six percent of all cases underwent surgery alone, 39% underwent treatment which included pelvic RT, and 17% underwent treatment which included chemotherapy. Pelvic recurrence was reduced significantly by radiotherapy in Stages I, II, and III (19% recurrence with no RT vs 7% recurrence with RT, P < 0.005). Chemotherapy improved overall survival, but made little difference in distant relapse rates. CONCLUSIONS: Stage Ia cases treated by surgery alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. Patients with Ib, Ic, II, and III have significantly lower pelvic failure rates if treated with pelvic radiation, but still have a high distant failure rate. Systemic therapy did not significantly improve distant relapse-free survival, but did extend overall survival. Stage IV patients usually died within 6 months with a few responding to systemic chemotherapy. These results suggest that there is a need for randomized trials for these patients.
A knowledge-based expert system was developed for the purpose of improving radiotherapy planning efficiency for a standardized, tangential breast technique. Treatment parameters pertaining to 150 previously planned patients were used for correlating the midplane breast contour of a new patient with an appropriate set of tangential beam weights and wedge angles; other treatment parameters including, planning target volume and isocenter, were specified by a radiation oncologist. Treatment plans generated by the expert system approach and a traditional, dosimetric approach were compared and rated prospectively in 45 patients. In addition, planning time was measured for both approaches. A performance rating of 97% was achieved for the expert system, in which an artificial neural network was used to correlate breast contours to treatment parameters, and approximately 30 minutes per patient was saved in treatment planning time. This high performance rating validated various assumptions concerning the expert system: namely, that the resultant dose distribution was not influenced by tangential field width (within the range of 7 to 12 cm), nominal beam energy (6 MV), or wedge type (physical vs. enhanced dynamic). Hence, the knowledge base may be directly transferable to other cancer centers using the same breast technique, and suggests that a global resource of radiotherapy treatment plans as well as planning strategies, categorized by treatment site, stage, and technique, may be viable.
From June 1994 through September 1995, 17 patients with gynecologic cancer were entered into a feasibility study using elemental supplements (ES) during the course of pelvic radiotherapy. The level of compliance with the ES regimen was evaluated by assessing sachet counts and patients' weekly diaries. Diaries were also used to assess compliance with a modified diet program. Bowel function in 45 patients receiving radiotherapy outside this study was assessed concurrently. All patients were reviewed weekly to record bowel function, which was also recorded 1 year after radiotherapy. After treatment of all patients the grade, duration of enteritis, need for antidiarrheal agents, and the likelihood of resolution at 1 year after radiotherapy were analyzed. The study used compliance with the ES regimen as its primary endpoint. Compliance with the ES regimen was achieved in 76.5% of patients, and compliance with the modified diet was achieved regardless of whether the ES was tolerated. Patients not complying with the ES, or who did not receive ES, had higher grade diarrhea, which was longer in duration and was less likely to have resolved than patients in the compliant group. Elemental supplements are well tolerated when taken during a course of pelvic radiotherapy and cause a mild diarrhea, which resolves after treatment has been discontinued. The lack of enteritis 1 year later in patients who complied with ES suggests that reducing the grade of acute enteritis might influence the appearance of later bowel effects.
PURPOSE: To compare patient demographics, treatment resources, practice patterns, and outcome results for squamous cell carcinoma of the uterine cervix (SCC) between the 1978 and 1983 Patterns of Care studies (PCS) in the United States of America (USA) and a nonacademic center within a developing country. METHOD AND MATERIALS: Patient details (race, age, stage, and number per year), treatment used, and treatment outcome were retrieved from the charts of the 1160 cases registered at this center with SCC of the cervix between 1976 and 1985. Demographic variables and Kaplan-Meier survival estimates were calculated and compared with results from published PCS reviews. RESULTS: There is a significant difference in the racial group presentation of cervix cancer at this center compared with the PCS reviews (p < 0.005), and median ages are significantly lower at this center (t = p < 0.001). The proportion of patients with Stage III or more was significantly higher at this center than the PCS centers (24 vs. 47%, p < 0.001). There were also vast differences in facility resources. Fewer cases at this center underwent intracavitary insertions than at PCS centers. Mean Point A doses were significantly reduced for this center compared with the PCS reviews. Kaplan-Meier estimates were similar for Stage I and II in PCS centers and this center, but were inferior for this center in Stage III patients (p < 0.05 for OS and p < 0.01 for LC). Late morbidity rates were similar for both PCS centers and this center. CONCLUSION: PCS recommendations may be applicable to nonacademic centers within developing countries, if the latter use staging techniques that are consistent with the PCS staging guidelines.
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Endodermal sinus tumours (EST) of the lower female genital tract are uncommon malignancies. The majority of these involve the vagina and cervix, though there are a few case reports of tumours involving the vulva. These are usually either locally advanced or have metastatic disease present at initial diagnosis, and generally do badly on treatment. This case report discusses primary vulval involvement by EST. It shows that the absence of tumour markers can be misleading, and discusses the role of radiation and chemotherapy in the treatment of this rare disease.
Ninety-three patients treated by radical irradiation for stage A2, B and C1 carcinoma of the prostate between 1979 and 1988 at a joint radiotherapy service were reviewed. The average age was 63 years, 84% of the patients were white and on histological examination the tumours were well or moderately differentiated in 88% of cases. Treatment was with 5 fractions per week in 71% while the remainder received 3-4 fractions per week. At a median follow-up of 62 months, the 5-year survival rate was 83% and the relapse-free rate was 73% (life table). The most important prognostic factor was tumour grade. In patients with grade 1 and 2 tumours, the 5-year survival rate and relapse-free rate was 91% and 76% respectively, while the survival for grade 3 tumour was 60% and 22% respectively (P less than 0.05 logrank). There was a suggestion that patients diagnosed by trans-rectal needle biopsy did better than those diagnosed by trans-urethral resection, but this was not statistically significant. Disease stage did not influence survival. The crude late complication rate was 10% but this was significantly related to the use of less than 5 fractions of radiation per week. A separate group of 13 patients with local disease who had had failed previous hormonal treatment were not analysed. Their 5-year survival rate was 19%, which is statistically significantly worse (P less than 0.001 logrank).
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