Regarding Ng et al.: Defining the role of adjuvant radiotherapy for high-risk stage I endometrial patients.
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Brachytherapy↗
Biomedical subjects
D G Petereit
Publications and source records attributed to D G Petereit.
Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer.
BACKGROUND AND PURPOSE: This paper investigates the outcome using different dose/fractionation schedules in high dose rate (HDR) post-operative vaginal vault radiotherapy in patients with low to intermediate risk endometrial cancer. MATERIALS AND METHODS: The world literature was reviewed and thirteen series were analyzed representing 1800 cases. RESULTS: A total of 12 vaginal vault recurrences were identified representing an overall vaginal control rate of 99.3%. A wide range of dose fractionation schedules and techniques have been reported. In order to analyze a dose response relationship for tumor control and complications, the biologically effective doses to the tumor and late responding tissues were calculated using the linear quadratic model. A threshold was identified for complications, but not vaginal control. While dose fractionation schedules that delivered a biologically effective dose to the late responding tissues in excess of 100 Gy(3) (LQED=60 Gy) predicted for late complications, dose fractionation schedules that delivered a modest dose to the vaginal surface (50 Gy(10) or LQED=30 Gy) appeared tumoricidal with vaginal control rates of at least 98%. CONCLUSIONS: By using convenient, modest dose fractionation schedules, HDR vaginal vault - brachytherapy yields very high local control and extremely low morbidity rates.
Brachytherapy↗
Complete surgical staging in endometrial cancer provides prognostic information only.
Endometrial cancer is the most common gynecologic malignancy in the United States. Surgical resection provides the best chance for cure and guides the potential need for adjuvant therapy. Controversy exists regarding the extent of surgical staging, in particular, the necessity and rationale for removing or sampling the draining lymphatics. An emerging practice in the United States is to perform more aggressive lymph node dissections. The data indicate that surgical staging provides prognostic information only and may indirectly influence survival only through guiding adjuvant therapy.
Endometrial Neoplasms↗
Gynecologic cancer: evolving management issues. Introduction.
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Female↗
Radiation injury from x-ray exposure during brachytherapy localization.
Two patients developed skin ulcers secondary to high doses of diagnostic-energy x rays received during localization procedures as part of brachytherapy treatments. Both were morbidly obese and diabetic. The obesity led to the delivery of estimated skin doses of 83 Gy in one case and 29 Gy in the other in attempts to produce readable images on localization radiographs. This report discusses the factors leading to the injuries, the progression of the injuries over time, and the variables involved in the localization procedures with the aim of preventing future mishaps. The greatest contribution to the large skin dose was the need, with the equipment available, to use multiple exposures to produce a single film, because of the effect of the resultant reciprocity failure.
Brachytherapy↗
High-dose-rate versus low-dose-rate brachytherapy in the treatment of cervical cancer: analysis of tumor recurrence--the University of Wisconsin experience.
PURPOSE: To retrospectively compare the clinical outcome for cervical cancer patients treated with high-dose-rate (HDR) vs. low-dose-rate (LDR) brachytherapy. METHODS AND MATERIALS: One hundred ninety-one LDR patients were treated from 1977 to 1988 and compared to 173 HDR patients treated from 1989 to 1996. Patients of similar stage and tumor volumes were treated with identical external beam fractionation schedules. Brachytherapy was given in either 1 or 2 LDR implants for the earlier patient cohort, and 5 HDR implants for the latter cohort. For both patient groups, Point A received a minimum total dose of 80 Gy. The linear-quadratic formula was used to calculate the LDR dose-equivalent contribution to Point A for the HDR treatments. The primary endpoints assessed were survival, pelvic control, relapse-free survival, and distant metastases. Endpoints were estimated using the Kaplan-Meier method. Comparisons between treatment groups were performed using the log-rank test and Cox proportional hazards models. RESULTS: The median follow-up was 65 months (2 to 208 months) in the LDR group and 22 months (1 to 85 months) in the HDR group. For all stages combined there was no difference in survival, pelvic control, relapse-free survival, or distant metastases between LDR and HDR patients. For Stage IB and II HDR patients, the pelvic control rates were 85% and 80% with survival rates of 86% and 65% at 3 years, respectively. In the LDR group, Stage IB and II patients had 91% and 78% pelvic control rates, with 82% and 58% survival rates at 3 years, respectively. No difference was seen in survival or pelvic control for bulky Stage I and II patients combined (>5 cm). Pelvic control at 3 years was 44% (HDR) versus 75% (LDR) for Stage IIIB patients (p = 0.002). This difference in pelvic control was associated with a lower survival rate in the Stage IIIB HDR versus LDR population (33% versus 58%, p = 0.004). The only major difference, with regard to patient characteristics, between the Stage IIIB patients was the incidence of hydronephrosis in the HDR vs. LDR group--28% vs. 12%, respectively (p = 0.05). For Stage IIIB patients treated with HDR, our analysis suggested that pelvic control rates improved when the first brachytherapy insertion was performed after the majority of external beam radiotherapy had been delivered. CONCLUSION: Similar outcome was observed for Stage IB and II patients treated with either HDR or LDR brachytherapy-regardless of tumor volume. However, poorer survival and pelvic control rates were observed for Stage IIIB patients treated with HDR brachytherapy. If HDR is used for Stage IIIB patients, our results suggest the majority of external beam radiotherapy should be delivered prior to initiating the brachytherapy to allow for adequate tumor regression. HDR brachytherapy is more convenient for patients, decreases the radiation exposure for health care workers, and should be considered a standard therapy for women with Stage I or II cervical cancer.
Adult↗
Literature analysis of high dose rate brachytherapy fractionation schedules in the treatment of cervical cancer: is there an optimal fractionation schedule?
PURPOSE: A literature review and analysis was performed to determine whether or not efficacious high dose rate (HDR) brachytherapy fractionation schedules exist for the treatment of cervical cancer. METHODS AND MATERIALS: English language publications from peer reviewed journals were assessed to calculate the total contribution of dose to Point A from both the external and intracavitary portions of radiation for each stage of cervical cancer. Using the linear quadratic formula, the biologically effective dose to the tumor, using an alpha/beta = 10, was calculated to Point A (Gy10) in order to determine a dose response relationship for local control and survival. Significant complications were assessed by calculating the dose to the late-responding tissues at Point A using an alpha/beta = 3 (Gy3) as a surrogate for normal tissue tolerance, since few publications list the actual bladder and rectal doses. RESULTS: For all stages combined, the median external beam fractionation schedule to Point A was 40 Gy in 20 fractions, while the median HDR fractionation schedule was 28 Gy in 4 fractions. For stages IB, IIB, and IIIB the median biologically effective dose to Point A (Gy10) was 96, 96 and 100 Gy10s, respectively. No correlation was identified between Point A BED (Gy10s) to either survival or pelvic control. A dose response relationship could also not be identified when correlating Point A Gy3s to complications. CONCLUSION: A dose response relationship could not be identified for either tumor control nor late tissue complications. These findings do not necessarily question the validity of the linear quadratic model, as much as they question the quality of the current HDR brachytherapy literature as it is currently presented and reported. Most of the HDR publications report inadequate details of the dose fractionation schedules. Only a minority of publications report significant complications using the actuarial method. In the future, all HDR publications for the treatment of cervical cancer should provide accurate fractionation details for each stage of disease, while reporting actuarial complication rates. The optimal fractionation schedule for treating cervical cancer using HDR brachytherapy is still unknown, and presently can be based only on single institutions with significant experience.
Brachytherapy↗
Perioperative morbidity and mortality of high-dose-rate gynecologic brachytherapy.
PURPOSE: To determine the 30-day morbidity and mortality rates for patients with an intact uterus undergoing high-dose-rate (HDR) brachytherapy, and to assess risk factors which may predict for these potentially life-threatening complications. METHODS AND MATERIALS: From August 1989 to December 1994, 128 cervical and 41 medically inoperable endometrial cancer patients were treated with 5 outpatient weekly HDR brachytherapy insertions. Patients with cervical cancer also were treated with external beam radiotherapy. Acute events that resulted in either hospitalization (morbidity) or death (mortality) within 30 days of the implant were analyzed. Univariate and multivariate analyses were performed to identify risk factors. RESULTS: Overall there were 16 acute events in 169 patients (9.5%). The overall morbidity and mortality rates for the cervical and endometrial patients were 5.5%, 1.6%, 7.3%, and 9.8%, respectively. The following factors were significant by univariate analysis: age per decade, American Society of Anesthesiologists (ASA) score, Karnofsky Performance Status (KPS), significant medical history, diagnosis of cervical vs. endometrial cancer, and mean time exceeding 160 minutes for the procedure. Since age was the most significant predictive factor (p = 0.0003), bivariate analyses were performed by adjusting for age. In these analyses only ASA and KPS maintained significance, while a positive medical history was of borderline significance (p = 0.07). CONCLUSION: The morbidity and mortality rates observed in gynecologic patients selected for HDR brachytherapy were similar to low-dose-rate, but higher than other HDR reports. Reasons for this include a higher risk population, especially those with medically inoperable endometrial cancer. In the cervical cancer patients, some of the complications may have also been a result of the external beam portion of the radiation. In order to minimize the acute complications observed in the present HDR brachytherapy system, the following changes have been implemented: appropriate patient selection, anesthesiology involvement to monitor conscious sedation for high-risk patients, external beam radiotherapy alone in patients at extremely high risk, deep vein thrombosis (DVT) prophylaxis, use of intraoperative ultrasound, shorter duration in the brachytherapy suite, and preradiation treatment plans (plans executed prior to the insertion) if applicable. Finally, this analysis suggests that these procedures should be performed in a hospital-based setting where appropriate support is available.
Adult↗
High-dose-rate brachytherapy for medically inoperable stage I endometrial cancer.
PURPOSE: The objective of this study was to determine the efficacy of high-dose-rate (HDR) brachytherapy in 36 medically inoperable patients with stage I endometrial cancer. METHODS AND MATERIALS: From October 1989 to August 1997, 36 patients presented with clinical stage I inoperable endometrial cancer. Surgery was precluded because of obesity and/or poor cardio-pulmonary reserve. Obesity was assessed using the body mass index (BMI) scale (kg/m2). Patients received 5 weekly HDR outpatient brachytherapy applications while under intravenous conscious sedation. Three-year clinical endpoints were calculated using the Kaplan and Meier method. Grade 3 and above complications were scored using the Radiation Therapy Oncology Group system. RESULTS: The median age, Karnofsky performance status, BMI, and weight were 65 years old, 80%, 47 kg/m2, and 268 lbs, respectively. Nineteen patients were inoperable due to morbid obesity (median weight and BMI: 316 lbs and 56 kg/m2) while the remaining patients had other significant medical problems. Two patients died from acute cardiovascular events within 30 days of the last insertion. With a median follow-up of 32 months the 3-year uterine control, disease-free survival, survival, and complications were 88, 85, 65, and 21%, respectively. CONCLUSION: Excellent uterine control rates (88%) were achieved using HDR brachytherapy for patients with medically inoperable endometrial cancer, but with significant acute and late morbidities. These toxicities were observed in a previous interim analysis that resulted in major modifications of the HDR program. No severe complications have developed since these changes were implemented. The current approach used for these challenging inoperable patients is a viable alternative to observation or hormonal therapy.
Adult↗
Phase II trial of hyperfractionated accelerated radiation therapy for nonresectable non-small-cell lung cancer: results of Eastern Cooperative Oncology Group 4593.
PURPOSE: To assess the feasibility, toxicity, and efficacy of hyperfractionated accelerated radiation therapy (HART) for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients from six institutions with stage IIIA or IIIB NSCLC were enrolled between November 1993 and August 1995. Radiation therapy (total dose, 57.6 Gy in 36 fractions) was delivered over 15 days with the use of three daily fractions with a 4-hour interval between fractions and an 8-hour interval between on-cord fields. Patients were not treated on weekends. RESULTS: Twenty-eight patients (93%) completed radiation therapy. Treatment-related toxicities of grade 3 or greater included esophagitis in six patients and grade 3 skin reaction in three patients. The overall objective response rate was 54%, and the response rate within the radiation field was 64%. With a minimum follow-up of 19 months in surviving patients, the median survival and 1-year survival rate are 13 months and 57%, respectively. The median relapse-free survival and 1-year relapse-free survival rate are 7 months and 23%, respectively. No transverse myelitis or late toxicities of grade 4 or greater have been observed. CONCLUSION: HART, delivered to a total dose of 57.6 Gy over 15 total days, is practical and well tolerated. Survival appears similar to that seen with modern combined modality regimens. A phase III trial is under way.
Aged↗
Manpower issues and training program directions in radiation oncology.
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Education, Medical, Graduate↗
The adverse effect of treatment prolongation in cervical carcinoma.
PURPOSE: Proliferation of surviving tumor clonogens during a course of protracted radiation therapy may be a cause of local failure in cervical carcinoma. The effect of total treatment time was analyzed retrospectively in relation to pelvic control and overall survival for squamous cell carcinomas of the uterine cervix. METHODS AND MATERIALS: Two hundred and nine patients (Stage IB-IIIB) treated with a combination of external beam and low dose rate intracavitary irradiation were evaluable for study. Multivariate analysis and Kaplan-Meier statistical methods were used to determine the effect of treatment time on pelvic control and survival at 5 years. RESULTS: The median treatment duration was 55 days. For all stages combined, the 5-year survival and pelvic control rates were significantly different with treatment times < 55 days vs. > or = 55 days: 65 and 54% (p = 0.03), 87 and 72% (p = 0.006), respectively. By stage, a shorter treatment duration (i.e., < 55 days vs. > or = 55 days) was significant for 5-year overall survival and pelvic control for Stages IB/IIA and III, but not for Stage IIB: Stage IB/IIA (81 and 67%, 96 and 84%), Stage III disease (52 and 42%, 76 and 55%) and Stage IIB (43 and 50%, 74 and 80%, respectively). Survival decreased 0.6%/day and pelvic control decreased 0.7%/day for each additional day of treatment beyond 55 days for all stages of disease. Additionally, significant late complications were not influenced by treatment time. CONCLUSION: These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients with cervical carcinoma. This is consistent with emerging data from other institutions. Therapeutic implications include avoidance of unnecessary treatment breaks, the design of fractionation schemes that decrease treatment duration, and possibly the use of tumor cytostatic drugs during conventional radiation.
Brachytherapy↗
Slowing proliferation in head and neck tumors: in vitro growth inhibitory effects of the polyamine analog BE-4-4-4-4 in human squamous cell carcinomas.
PURPOSE: These preclinical studies were carried out to examine the potential of the antiproliferative polyamine analog 1,19-bis-(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) to serve as a therapy adjuvant to radiation for patients with rapidly dividing tumors of the head and neck (H&N). METHODS AND MATERIALS: Cytostatic and cytotoxic effects of this polyamine analog were investigated in three squamous cell carcinoma (SCC) cell lines derived from human H&N tumors. RESULTS: Growth inhibition was achieved in all cell lines within 3-4 days of continuous 10 microM drug exposure, and inhibition of cell cycle proliferation kinetics was confirmed via flow cytometry. Cytotoxicity was pronounced (3-4 log cell kill) in the SCC-38 and SCC-4Y cell lines with continuous 10 microM analog exposure over 5 days, and was minimal in the SCC-13Y cell line. No demonstrable effect of BE-4-4-4-4 on single dose radiation survival was identified in any SCC cell line. Ornithine decarboxylase (ODC) activity was rapidly inhibited (1-2 h) following 10 microM BE-4-4-4-4 exposure in all SCC cell lines (approximately 90%), whereas identical exposure to 10 microM difluoromethylornithine (DFMO) induced animal ODC inhibition (approximately 10%). Dose-dependent depletion of endogenous polyamines (putrescine, spermidine, spermine) was achieved in all SCC cell lines following 1 microM and 10 microM BE-4-4-4-4 exposures. Difluoromethylornithine was significantly less potent than BE-4-4-4-4 in its capacity to deplete endogenous polyamines, with no measureable depletion of spermine pools even with 5 mM x 48 h DFMO exposures. CONCLUSIONS: These data evaluate cytostatic and cytotoxic properties of the polyamine analog BE-4-4-4-4 in human SCCs, and suggest a role for investigation of such agents as an adjuvant to radiation in the therapeutic approach to rapidly dividing human tumors such as those that occur in the H&N.
Carcinoma, Squamous Cell↗
A comparison of the efficacy and complication rates of low dose-rate versus high dose-rate brachytherapy in the treatment of uterine cervical carcinoma.
PURPOSE: To compare the outcome and complication rates for treatment of uterine cervical carcinoma with low dose-rate (LDR) vs. high dose-rate (HDR) brachytherapy at the University of Wisconsin Comprehensive Cancer Center (UWCCC). METHODS AND MATERIALS: One-hundred ninety-eight evaluable patients with cervical carcinoma, Stages IB to IIIB, treated with curative intent with a combination of megavoltage teletherapy and LDR brachytherapy from 1977 to 1988 were the subject of an initial review. In 1989, a HDR treatment program was initiated where all patients with cervical carcinoma were subsequently treated with a combination of HDR brachytherapy and teletherapy. Using the linear-quadratic model (LQ), the dose and schedule of HDR brachytherapy and teletherapy were designed to give similar tumor control and late effects as LDR therapy. Technically, the HDR schedule required meticulous attention to treatment geometry to limit severe late effects. Forty patients treated with the HDR program with 2-4 year follow-up were reviewed and compared to the previous LDR patient group. The LDR and HDR treatment groups were comparable with regards to age, weight, stage distribution, bulk of disease, and histology. RESULTS: No significant difference in survival was found between the LDR and HDR groups with 3-year actuarial overall survival being 66% and 77%, respectively. Three-year actuarial pelvic control rates were similar at 80% and 77% for the LDR and HDR groups, respectively. No significant difference in late treatment complications requiring hospitalization or surgery was found between the two treatment groups with a complication rate of 10% (20/198) for the LDR patients and 2.5% (1/40) for the HDR patients. CONCLUSION: As predicted by our LQ calculations, treatment results for LDR and HDR brachytherapy were similar with respect to survival, pelvic control and late complications in the treatment of cervical carcinoma. The HDR brachytherapy program at the UWCCC appears to be a safe and effective alternative to LDR therapy in the treatment of cervical carcinoma.
Adolescent↗
Optimizing the dose rate and technique in cervical carcinoma--balancing cases versus complications.
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Brachytherapy↗
Combining polyamine depletion with radiation therapy for rapidly dividing head and neck tumors: strategies for improved locoregional control.
PURPOSE: Locoregional control is adversely affected as clonogens from rapidly proliferating tumors repopulate during a course of radiation therapy. The cytostatic agent alpha-difluoromethylornithine (DFMO) was investigated for its capacity to slow proliferation kinetics in human squamous cell carcinomas (SCC) of the head and neck (H&N), with the ultimate objective of improving locoregional control in rapidly dividing tumors treated with radiation therapy. METHODS AND MATERIALS: Three human SCC cell lines established from primary H&N tumors were evaluated in vitro (cell culture) and in vivo (SCC tumor xenografts in athymic mice) for the capacity of DFMO to induce growth inhibition. Flow cytometry analysis of SCC tumor growth kinetics and quantitative assessment of polyamine biosynthesis inhibition was performed to verify DFMO activity. DFMO effects on in vitro SCC radiosensitivity using clonogenic survival were also studied. RESULTS: A noncytotoxic exposure to DFMO (5mM x 72 hours) induced pronounced growth inhibition in all three SCC cell lines (70-90% at 7 days), and induced a 2-3 fold delay in volume doubling time for SCC tumor xenografts when administered orally in the drinking water (1.5%) to athymic mice. Kinetic analysis via flow cytometry confirmed that DFMO produced a lengthening of SCC cell cycle times, but did not alter in vitro radiosensitivity. Inhibition of ornithine decarboxylase (ODC) activity and depletion of endogenous polyamines (putrescine and spermidine), were confirmed in normal tissue (mouse skin) and in human SCC tumor xenografts of athymic mice receiving continuous oral DFMO. CONCLUSION: These data indicate that antiproliferative agents, such as DFMO, are capable of altering human SCC growth kinetics without altering intrinsic radiosensitivity. Such kinetic modulation may therefore provide a strategy to reduce the adverse impact of tumor cell proliferation during a radiotherapy treatment course for rapidly dividing tumors such as those in the H&N.
Animals↗
Inguinofemoral radiation of N0,N1 vulvar cancer may be equivalent to lymphadenectomy if proper radiation technique is used.
PURPOSE: To update a previous retrospective study that compared inguinofemoral irradiation (N = 23) to lymphadenectomy (N = 25) for N0,N1 vulvar carcinoma with more patients and longer follow-up. These results, unlike the recent randomized Gynecologic Oncology Group (GOG study), suggest that radiation is a viable alternative to groin dissection, and the differences may be explained on the basis of irradiation technique. METHODS AND MATERIALS: Based on a growing body of data supporting control of subclinical nodal disease with irradiation in vulvar cancer, the decision was made to offer patients with squamous cell carcinoma of the vulva and clinically negative groins (N0,N1), either lymphadenectomy or inguinofemoral irradiation based on clinical factors. Because of the acute skin reaction and possible underdosing of deep femoral nodes with electrons as used in the GOG study, opposed photon fields to 50 Gy were used. From 1983 to 1991, 48 patients underwent a radical vulvectomy followed by either lymphadenectomy (Group I, n = 25) or inguinofemoral irradiation (Group II, n = 23). RESULTS: The actuarial nodal control was 100% in Group I and 91% in Group II (p = 0.14). In addition, there was no difference in cause specific survival at 3 years (96% and 90%, respectively, p = 0.47). The morbidity of lymphadenectomy (Group I) included: 16% lymphedema, 16% seromas, 44% infection, and 68% wound separation. In the irradiated patients (Group II), 16% developed lymphedema and only 9% had a significant skin reaction. CONCLUSION: Based on this analysis of local control and survival with longer follow-up and more patients, irradiation of the N0, N1 inguinofemoral nodes may be a viable alternative to lymphadenectomy for squamous cell carcinoma of the vulva if proper radiation technique and dose are used. In addition, the acute and delayed morbidity of lymphadenectomy exceeds that of irradiation.
Aged↗
A retrospective review of nodal treatment for vulvar cancer.
From 1983 to 1990, 42 clinical N0, N1 patients with invasive squamous cell carcinoma of the vulva underwent surgery for the primary cancer, followed by nonrandomized assignment to either surgery or radiation therapy for nodal management. This is a retrospective analysis reviewing treatment outcome and complications of inguinofemoral dissection versus photon irradiation. Group I (N = 24) underwent either bilateral or unilateral inguinofemoral dissection; Group II (N = 18) underwent bilateral groin irradiation. The 3-year disease-free survival was 84.5% and 79.7% for Group I and II (p = 0.74). The nodal failure rate at 3 years was not significantly different. The postoperative complications in the surgically treated nodes were: 17% seromas, 46% wound infection, and 71% wound separation. Of those patients developing either an infection or wound separation, 41% required daily wound care for more than 2 weeks by a visiting nurse after discharge. Only 1 of 18 (6%) irradiated patients developed a clinically significant skin reaction. The median time for complete skin/wound healing was 8 weeks (range 4-24 weeks) in Group I and 2 weeks (range 2-6 weeks) in Group II. Late postoperative complications in the surgically treated patients included meralgia paresthetica (8%) and lymphedema (12%); 1 (6%) Group II patient developed lymphedema. Based on this limited retrospective review, we conclude that inguinofemoral radiation achieves reasonable local control and may represent an alternative to surgery in selected patients. The acute and delayed morbidity of lymphadenectomy exceeds that of irradiation.
Aged↗