Search PubMed⌕ Search

Biomedical subjects

P W Grigsby

Publications and source records attributed to P W Grigsby.

At least 19 recordsLinked to original sources
PubMed2001

Long-term follow-up of RTOG 92-10: cervical cancer with positive para-aortic lymph nodes.

PURPOSE: The purpose of this study was to evaluate the late toxicity and efficacy of twice-daily external irradiation to the pelvis and lumbar para-aortic region with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. PATIENTS AND METHODS: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and lumbar para-aortic lymph nodes (simultaneously) at 4-6-h intervals, 5 days per week. The total external radiation doses were 24-48 Gy to the whole pelvis, 12-36 Gy parametrial boost, and 48 Gy to the lumbar para-aortic region with an additional boost to a total dose 54-58 Gy to the positive para-aortic lymph node(s). One or two intracavitary implants were performed to deliver a minimum total dose of 85 Gy to point A. Cisplatin (75 mg/m(2); Days 1, 22, and 43) and 5-fluorouracil (1,000 mg/m(2)/24 h x 4 consecutive days, beginning on Days 1, 22, and 43) were given for two or three cycles. RESULTS: Thirty patients with clinical Stages I-IV carcinoma of the cervix with biopsy-proven para-aortic lymph node metastases were enrolled in this study. Hyperfractionated external irradiation was completed in 87% (26 of 30). Brachytherapy was given in two implants to 47% (14 of 30) and in one implant to 33% (10 of 30); 13% (4 of 30) did not receive brachytherapy, 1 patient had three implants, and 1 had five high-dose-rate implants. Radiotherapy was completed per protocol in 70%. Three cycles of chemotherapy were given to 23% (7 of 30); 73% (22 of 30) received two cycles, and 1 patient did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Acute toxicity from radiotherapy was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. Late toxicity was Grade 1 in 10%, Grade 2 in 17%, Grade 3 in 7%, and Grade 4 in 17%. Grade 5 toxicity occurred in 1 patient during the course of therapy, but none had a late Grade 5 toxicity. The median follow-up time for the 7 patients alive at the time of last follow-up was 57 months. The overall survival estimates were 46% at 2 years and 29% at 4 years. The probability of local-regional failure was 40% at 1 year and 50% at 2 and 3 years. The probability of disease failure at any site was 46% at 1 year, 60% at 2 years, and 63% at 3 years. CONCLUSION: The results suggest that twice-daily external irradiation to the pelvis and lumbar para-aortic region with brachytherapy and concurrent chemotherapy resulted in an unacceptably high rate (17%, 5 of 29) of Grade 4 late toxicity. One patient died of acute complications of therapy. The survival estimates seem no better than standard fractionation irradiation without chemotherapy.

Adenocarcinoma↗
PubMed2001

Intensity-modulated radiation therapy (IMRT) reduces small bowel, rectum, and bladder doses in patients with cervical cancer receiving pelvic and para-aortic irradiation.

PURPOSE: The emergent use of combined modality approach (chemotherapy and radiation therapy) for the treatment of patients with cervical cancer is associated with significant gastrointestinal and genitourinary toxicity. Intensity-modulated radiation therapy (IMRT) has the potential to deliver adequate dose to the target structures while sparing the normal organs and could also allow for dose escalation to grossly enlarged metastatic lymph node in pelvic or para-aortic area without increasing gastrointestinal/genitourinary complications. We conducted a dosimetric analysis to determine if IMRT can meet these objectives in the treatment of cervical cancer. METHODS AND MATERIALS: Computed tomography scan studies of 10 patients with cervical cancer were retrieved and used as anatomic references for planning. Upon the completion of target and critical structure delineation, the imaging and contour data were transferred to both an IMRT planning system (Corvus, Nomos) and a three-dimensional planning system (Focus, CMS) on which IMRT as well as conventional planning with two- and four-field techniques were derived. Treatment planning was done on these two systems with uniform prescription, 45 Gy in 25 fractions to the uterus, the cervix, and the pelvic and para-aortic lymph nodes. Normalization was done to all IMRT plans to obtain a full coverage of the cervix with the 95% isodose curve. Dose-volume histograms were obtained for all the plans. A Student's t test was performed to compute the statistical significance. RESULTS: The volume of small bowel receiving the prescribed dose (45 Gy) with IMRT technique was as follows: four fields, 11.01 +/- 5.67%; seven fields, 15.05 +/- 6.76%; and nine fields, 13.56 +/- 5.30%. These were all significantly better than with two-field (35.58 +/- 13.84%) and four-field (34.24 +/- 17.82%) conventional techniques (p < 0.05). The fraction of rectal volume receiving a dose greater than the prescribed dose was as follows: four fields, 8.55 +/- 4.64%; seven fields, 6.37 +/- 5.19%; nine fields, 3.34 +/- 3.0%; in contrast to 84.01 +/- 18.37% with two-field and 46.37 +/- 24.97% with four-field conventional technique (p < 0.001). The fractional volume of bladder receiving the prescribed dose and higher was as follows: four fields, 30.29 +/- 4.64%; seven fields, 31.66 +/- 8.26%; and nine fields, 26.91 +/- 5.57%. It was significantly worse with the two-field (92.89 +/- 35.26%) and with the four-field (60.48 +/- 31.80%) techniques (p < 0.05). CONCLUSION: In this dosimetric study, we demonstrated that with similar target coverage, normal tissue sparing is superior with IMRT in the treatment of cervical cancer.

Female↗
PubMed2001

Image-based dose planning of intracavitary brachytherapy: registration of serial-imaging studies using deformable anatomic templates.

PURPOSE: To demonstrate that high-dimensional voxel-to-voxel transformations, derived from continuum mechanics models of the underlying pelvic tissues, can be used to register computed tomography (CT) serial examinations into a single anatomic frame of reference for cumulative dose calculations. METHODS AND MATERIALS: Three patients with locally advanced cervix cancer were treated with CT-compatible intracavitary (ICT) applicators. Each patient underwent five volumetric CT examinations: before initiating treatment, and immediately before and after the first and second ICT insertions, respectively. Each serial examination was rigidly registered to the patient's first ICT examination by aligning the bony anatomy. Detailed nonrigid alignment for organs (or targets) of interest was subsequently achieved by deforming the CT exams as a viscous-fluid, described by the Navier-Stokes equation, until the coincidence with the corresponding targets on CT image was maximized. In cases where ICT insertion induced very large and topologically complex rearrangements of pelvic organs, e.g., extreme uterine canal reorientation following tandem insertion, a viscous-fluid-landmark transformation was used to produce an initial registration. RESULTS: For all three patients, reasonable registrations for organs (or targets) of interest were achieved. Fluid-landmark initialization was required in 4 of the 11 registrations. Relative to the best rigid bony landmark alignment, the viscous-fluid registration resulted in average soft-tissue displacements from 2.8 to 28.1 mm, and improved organ coincidence from the range of 5.2% to 72.2% to the range of 90.6% to 100%. Compared to the viscous-fluid transformation, global registration of bony anatomy mismatched 5% or more of the contoured organ volumes by 15-25 mm. CONCLUSION: Pelvic soft-tissue structures undergo large deformations and displacements during the external-beam and multiple-ICT course of radiation therapy for locally advanced cervix cancer. These changes cannot be modeled by the conventional rigid landmark transformation method. In the current study, we found that the deformable anatomic template registration method, based on continuum-mechanics models of deformation, successfully described these large anatomic shape changes before and after ICT. These promising modeling results indicate that realistic registration of the cumulative dose distribution to the organs (or targets) of interest for radiation therapy of cervical cancers is achievable.

Algorithms↗
PubMed2001

Lymph node staging by positron emission tomography in patients with carcinoma of the cervix.

PURPOSE: The aim of this study was to compare the results of computed tomography (CT) and positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) for lymph node staging in patients with carcinoma of the cervix and to evaluate the relationship of the imaging findings to prognosis. PATIENTS AND METHODS: We retrospectively compared the results of CT lymph node staging and whole-body FDG-PET in 101 consecutive patients with carcinoma of the cervix. Patients were treated with standard irradiation and chemotherapy (as clinically indicated) and observed at 3-month intervals for a median of 15.4 months (range, 2.5 to 30 months). Progression-free survival was evaluated by the Kaplan-Meier method. RESULTS: CT demonstrated abnormally enlarged pelvic lymph nodes in 20 (20%) and para-aortic lymph nodes in seven (7%) of the 101 patients. PET demonstrated abnormal FDG uptake in pelvic lymph nodes in 67 (67%), in para-aortic lymph nodes in 21 (21%), and in supraclavicular lymph node in eight (8%). The 2-year progression-free survival, based solely on para-aortic lymph node status, was 64% in CT-negative and PET-negative patients, 18% in CT-negative and PET-positive patients, and 14% in CT-positive and PET-positive patients (P <.0001). A multivariate analysis demonstrated that the most significant prognostic factor for progression-free survival was the presence of positive para-aortic lymph nodes as detected by PET imaging (P =.025). CONCLUSION: This study demonstrates that FDG-PET detects abnormal lymph node regions more often than does CT and that the findings on PET are a better predictor of survival than those of CT in patients with carcinoma of the cervix.

Actuarial Analysis↗
PubMed2001

Acute phase response during radiotherapy.

PURPOSE: The acute phase response is characterized by changes in the plasma concentrations of a number of liver-synthesized proteins, one of which is C-reactive protein (CRP). The existence of these changes in the plasma profile underlies the change in erythrocyte sedimentation rate (ESR). Acute phase response itself is an illness and may result from immunologic reactions and inflammatory processes. This study is designed to determine whether the CRP level and ESR increase during radiotherapy and whether their rise correlates with acute and late radiation morbidity. METHODS AND MATERIALS: Between April 1997 and October 1998, 51 patients with the diagnosis of endometrium and cervical cancer were treated with surgery and postoperative radiotherapy. Median age at the time of radiotherapy was 52 (range, 26-73) years. Thirty patients received pelvic radiotherapy, and 21 patients were treated by pelvic-paraaortic irradiation. A total dose of 50.4 Gy to the pelvis and 45 Gy to the paraaortic field were delivered in conventional fraction. Erythrocyte sedimentation rates and CRP levels were studied before, during, and at the end of radiotherapy. RESULTS: The mean ESR measurements before and after radiotherapy were 40 (8-100) and 52 (10-120), and mean CRP levels were 1.4 (0.12-9.8) and 2.7 (0.12-32.2), respectively. The statistical analysis yielded significant rise in ESR and CRP levels at the end of radiotherapy (p < 0.001). The increase was more prominent in patients who were irradiated through pelvic-paraaortic field than in patients with pelvic radiation (p = 0.005 and 0.028 respectively). CONCLUSION: Acute phase response was present during radiotherapy. Radiotherapy should be considered as a cause of increase in CRP level and ESR especially in clinical conditions where acute phase response is important.

Acute-Phase Reaction↗
PubMed2001

Can costs be measured and predicted by modeling within a cooperative clinical trials group? Economic methodologic pilot studies of the radiation therapy oncology group (RTOG) studies 90-03 and 91-04.

PURPOSE: To (1) measure radiation therapy costs for patients in randomized controlled clinical trials, (2) compare measured costs to modeling predictions, (3) examine cost distributions, and (4) assess feasibility of collecting economic data within a cooperative group. METHODS: The Radiation Therapy Oncology Group conducted economic pilot studies for two Phase III studies that compared fractionation patterns. Expected quantities of Current Procedural Terminology (CPT) codes and relative value units (RVU) were modeled. Institutions retrospectively provided procedure codes, quantities, and components, which were converted to RVUs used for Medicare payments. Cases were included if the radiation therapy quality control review judged them to have been treated per protocol or with minor variation. Cases were excluded if economic quality review found incomplete economic data. RESULTS: The median and mean RVUs were within the range predicted by the model for all arms of one study and above the predicted range for the other study. CONCLUSION: The model predicted resource use well for patients who completed treatment per protocol. Actual economic data can be collected for critical cost items. Some institutions experienced difficulty collecting retrospective data, and prospective collection of data is likely to allow wider participation in future Radiation Therapy Oncology Group economic studies.

Brain Neoplasms↗
PubMed2001

Radiation therapy for carcinoma of the cervix with biopsy-proven positive para-aortic lymph nodes.

PURPOSE: To evaluate local tumor control, cause-specific survival, patterns of relapse, and toxicity in patients with cervical cancer and positive para-aortic lymph nodes treated with radiation therapy alone. METHODS: This is a retrospective chart review of 43 patients with cervical cancer and biopsy-proven positive para-aortic lymph nodes treated with radiation therapy treated from 1965 to 1993. There were 15 patients with clinical Stage I disease, 12 with Stage II, and 16 with Stage III. Patients were treated with external irradiation to the pelvis and para-aortic regions combined with brachytherapy. None received chemotherapy. RESULTS: The 5-year overall survival rate was 32% and the median overall survival was 2.2 years. The 5-year cause-specific survival rate was 49% and the median cause-specific survival was 2.7 years. The cause-specific survivals at 5 years were 47% for Stage I, 64% for Stage II, and 46% for Stage III. Tumor recurrence occurred in 20 patients. The sites of recurrence were in the pelvis only in 3, the pelvis and distant metastasis in 9, and distant metastasis only in 8 patients. Severe, grade 3 complications occurred in 2 patients. One patient developed an enterovaginal fistulas and 1 developed radiation myelitis. CONCLUSION: Pelvic and para-aortic irradiation and brachytherapy resulted in a 49%, 5-year, cause-specific survival. Clinical tumor stage did not effect outcome. The majority of relapses occurred at distant sites. Toxicity was acceptable. Systemic chemotherapy should be considered as adjunctive therapy for these patients.

Adult↗
PubMed2001

Cervical tumor control evaluated with ICRU 38 reference volumes and integrated reference air kerma.

PURPOSE: The purpose of this investigation was to evaluate the relationship of ICRU 38 reference volumes and integrated reference air kerma to primary cervical tumor control. MATERIALS AND METHODS: This retrospective study includes 1253 women with carcinoma of the uterine cervix treated with radiotherapy. Patients were treated from 1959 to 1993 at the Mallinckrodt Institute of Radiology. There were 39 women with stage Ia disease, 211 with stage Ib1, 88 with stage Ib2, 580 with stage 2, and 335 with stage 3 disease. Most patients with stage Ia disease were treated with low dose rate brachytherapy alone. All other patients were treated with external irradiation and low dose rate brachytherapy. External irradiation doses ranged from 8.2-63.8 Gy to the whole pelvis and an additional parametrial boost to deliver a total of 65-75 Gy to Point P depending on tumor stage. Low dose rate brachytherapy was delivered to the primary tumor with doses ranging from 40x10(4)-60x10(4) Gy cm(2) (integrated reference air kerma; IRAK). Isodose reference volumes (60-160 Gy) and point A doses were determined for all patients. Tumor control was defined as control of the primary cervical cancer with or without failure at other pelvic or distant sites. RESULTS: The mean 60 Gy volume was calculated to be 139.5 cm(3) for stage Ia, 200.4 cm(3) for stage Ib1, 270.9 cm(3) for stage Ib2, 235 cm(3) for stage 2, and 293.4 cm(3) for stage 3. No patient with stage Ia disease had a failure in the cervix. For stage Ib1 tumors the mean 60 Gy volume was 219.1 cm(3) for those who failed in the cervix and 199.9 cm(3) for those who did not fail (P=0.73). For stage Ib2 tumors the mean 60 Gy volume was 354.4 cm(3) for those who failed and 260.2 cm(3) for those who did not fail (P=0.004). The mean 60 Gy volume was 249.3 cm(3) for those with stage 2 disease who failed and 233.8 cm(3) for those who did not fail (P=0.02). For patients with stage 3 cancer the mean 60 Gy volume was 321.6 cm(3) for those who failed and 287.3 cm(3) for those who did not fail (P=0.20). Reference volumes from 70-160 Gy were not statistically different within each stage for those who failed in the cervix compared to those who did not fail. Cervical recurrences by clinical stage did not have statistically significant differences for mean IRAK except for stage II disease (P=0.001). CONCLUSION: Analysis of the 60-160 Gy reference volumes and IRAK failed to demonstrate a consistent positive increasing correlation of these values to primary cervical tumor control.

Adenocarcinoma↗
PubMed2001

Current management of patients with invasive cervical carcinoma.

After the logic of evidence-based medicine, there are several conclusions to be reached from these recent prospective, randomized phase III clinical trials. Patients with stages IB2 and IIA cervical carcinoma, although technically manageable, should be treated with external pelvic irradiation and brachytherapy and weekly (cisplatin 40 mg/m2 x 6 wk), if it is suspected that the likelihood of positive lymph nodes or margins requiring adjuvant treatment after radical surgery would be significant. In those patients in whom the risks of either positive margins or lymph nodes are low, either radical surgery or radiation are equally efficacious options. A recent report that surveyed the Surveillance, Epidemiology, and End Results program database suggested that there may be a survival advantage for surgical intent-to-treat patients compared with the radiation intent-to-treat patients for tumors 4 cm or smaller in patients with stage IB and IIA cervical cancers. Certainly, toxicity criteria for these patients in terms of long-term problems need to be further examined. For those patients who undergo a radical hysterectomy and lymph node dissection, postoperative irradiation is indicated if high-risk factors such as large tumor size, lymph vascular space invasion, and deep stromal invasion are identified. Patients who are found to have positive lymph nodes, positive parametrial invasion, or positive margins at the time of hysterectomy should receive postoperative irradiation with chemotherapy. All other patients with more advanced clinical stages of cervical carcinoma should be treated with external pelvic irradiation, brachytherapy, and concurrent chemotherapy. Based on the results of the randomized studies, there appears to be no role for either hydroxyurea or fluorouracil. The chemotherapy agent of choice, at present, is cisplatin administered concurrently with irradiation at a dose of 40 mg/m2 weekly for 6 weeks. Concurrent chemotherapy should be avoided in patients with a poor performance status and other severe comorbidities, and these patients should be treated with irradiation alone. Further refinement of treatment for those patients who require combined chemo/radiation versus those with comorbidities such that combination chemotherapy is actually too toxic must be defined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Radiation exposure from outpatient radioactive iodine (131I) therapy for thyroid carcinoma.

CONTEXT: In May 1997, the US Nuclear Regulatory Commission (NRC) revised its patient release regulations, allowing for outpatient administration of larger activities of sodium iodide 131I than previously permitted. OBJECTIVE: To measure the radiation exposure to household members from patients receiving outpatient 131I therapy for thyroid carcinoma in accordance with the new regulations. DESIGN: Consecutive case series from October 1998 to June 1999. SETTING AND PATIENTS: Thirty patients who received outpatient 131I therapy following thyroidectomy for differentiated thyroid carcinoma were enrolled, along with their 65 household members and 17 household pets. MAIN OUTCOME MEASURE: Radiation exposure to household members and 4 rooms in each home, as monitored with dosimeters for 10 days following 131I administration. RESULTS: The patients received 131I doses ranging from 2.8 to 5.6 GBq (mean, 4.3 GBq). The radiation dose to 65 household members ranged from 0.01 mSv to 1.09 mSv (mean, 0.24 mSv). The dose to 17 household pets ranged from 0.02 mSv to 1.11 mSv (mean, 0.37 mSv). The mean dose to the 4 rooms ranged from 0.17 mSv (kitchen) to 0.58 mSv (bedroom). CONCLUSION: In our study, 131I doses to household members of patients receiving outpatient 131I therapy were well below the limit (5.0 mSv) mandated by current NRC regulations.

Adolescent↗
PubMed2000

Comparison of clinical outcome in black and white women treated with radiotherapy for cervical carcinoma.

BACKGROUND: The purpose of this investigation was to evaluate the significance of race on the cancer-specific survival outcome of women treated with radiotherapy for advanced-stage cancer of the uterine cervix. METHODS: Data from 922 women with cancer of the uterine cervix treated with radiotherapy were reviewed. Patients were treated at the Mallinckrodt Institute of Radiology from 1959 through 1993. There were 576 women with clinical Stage II cancer and 346 women with clinical Stage III cancer. All women were treated following standard medical care treatment policies according to the stage of their disease. Data were analyzed by race and known treatment-related prognostic factors. Overall and cancer-specific survivals were evaluated. RESULTS: The 5-year cancer-specific survivals for clinical Stage II were 66 and 61% (P = 0.56) for white and black women, respectively. The corresponding 5-year overall survivals were 60 and 51% (P = 0.02). The 5-year cancer-specific survivals for clinical Stage III were 38 and 47% (P = 0.34) for white and black women, respectively. The associated 5-year overall survivals were 32 and 40% (P = 0.37). No differences in treatment-related factors were identified. CONCLUSIONS: In a cancer treatment system where black and white women with clinical Stage II and III cancer of the uterine cervix are all treated with radiotherapy alone, following standard treatment policies, no significant difference in cancer-specific survival outcome is shown. Multivariate analysis revealed that clinical stage and overall treatment time are significant variables affecting the control of tumor by radiotherapy. Overall survivals for the two racial groups are different and may be related to other non-cancer-related factors.

Black People↗
PubMed1999

Lack of effect of tumor size on the prognosis of carcinoma of the uterine cervix Stage IB and IIA treated with preoperative irradiation and surgery.

PURPOSE: The purpose of this analysis was to evaluate the prognostic significance of cervical tumor size in patients with Stages Ib and IIa carcinoma of the cervix treated with preoperative irradiation and radical or conservative hysterectomy. METHODS AND MATERIALS: This study is a retrospective analysis of 177 patients. One hundred forty-one patients had Stage Ib and 36 patients had Stage IIa carcinoma of the cervix. All patients were treated with preoperative irradiation and surgery. Radiation therapy consisted of external pelvic irradiation and intracavitary brachytherapy; total doses ranged from 30 to 60 Gy to the pelvic sidewall and 60 to 70 Gy to point A. Surgery consisting of radical hysterectomy and lymph node dissection or a conservative hysterectomy and lymph node dissection was performed 4 to 6 weeks after completion of irradiation. RESULTS: The 5-year progression-free survivals were 80% for Stage Ib and 63% for Stage IIa (p = 0.03). The 5-year cumulative pelvic failure rates for Stage Ib were 16% for tumors <3 cm and 9% for tumors >3 cm (p = 0.90). The 5-year cumulative pelvic failure rates for Stage IIa were 22% for tumors <3 cm and 22% for tumors >3 cm (p = 0.75). The corresponding cumulative distant metastasis failure rates at 5 years for Stage Ib were 21% for tumors <3 cm and 21% for tumors >3 cm (p = 0.60). For patients with Stage IIa disease, the 5-year cumulative distant metastasis rates were 33% for tumors <3 cm and 36% for tumors >3 cm (p = 0.70). A multivariate analysis was performed to evaluate prognostic factors for the endpoint of progression-free survival. The variables that were analyzed were patient age, tumor histology, tumor size, clinical stage, point A and pelvic lymph node irradiation dose, and cervical tumor status and pelvic lymph node status at the time of hysterectomy. The variables that were found to be of independent significance for progression-free survival by multivariate analysis were pelvic lymph node irradiation dose (p <0.001), pelvic lymph node status at the time of hysterectomy (p = 0.01), and clinical stage (p = 0.02). Cervical tumor size at the time of diagnosis and the presence of tumor cells in the cervix in the hysterectomy specimen was not an independent prognostic factor by multivariate analysis. The overall severe complication rate was 11% for all patients. CONCLUSIONS: For this population of patients treated with preoperative irradiation and surgery, pelvic lymph node status at the time of hysterectomy and the preoperative irradiation dose to the pelvic lymph nodes are independent predictors of progression-free survival and the development of distant metastasis. The pretreatment cervical tumor size is of less importance for predicting progression-free survival and the development of distant metastasis but clinical stage is an important prognostic variable. These results are in contrast with those of surgery or irradiation alone, in which primary tumor size is a critical prognostic factor for all outcome parameters.

Adolescent↗
PubMed1999

Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation.

PURPOSE: To quantitate the impact of total doses of irradiation, dose rate, and ratio of doses to bladder or rectum and point A on sequelae in patients treated with irradiation alone for cervical cancer. METHODS AND MATERIALS: Records were reviewed of 1456 patients (Stages IB-IVA) treated with external-beam irradiation plus two low-dose rate intracavitary insertions to deliver 70 to 90 Gy to point A. Follow-up was obtained in 98% of patients (median, 11 years; minimum, 3 years; maximum, 30 years). The relationships among various dosimetry parameters and Grade 2 or 3 sequelae were analyzed. RESULTS: In Stage IB, the frequency of patients developing Grade 2 morbidity was 9%, and Grade 3 morbidity, 5%; in Stages IIA, IIB, III, and IVA, Grade 2 morbidity was 10% to 12% and Grade 3 was 10%. The most frequent Grade 2 sequelae were cystitis and proctitis (0.7% to 3%). The most common Grade 3 sequelae were vesicovaginal fistula (0.6% to 2% in patients with Stage I-III tumors), rectovaginal fistula (0.8% to 3%), and intestinal obstruction (0.8% to 4%). In the bladder, doses below 80 Gy correlated with less than 3% incidence of morbidity and 5% with higher doses (p = 0.31). In the rectosigmoid, the incidence of significant morbidity was less than 4% with doses below 75 Gy and increased to 9% with higher doses. For the small intestine, the incidence of morbidity was less than 1% with 50 Gy or less, 2% with 50 to 60 Gy, and 5% with higher doses to the lateral pelvic wall (p = 0.04). When the ratio of dose to the bladder or rectum in relation to point A was 0.8 or less, the incidence of rectal morbidity was 2.5% (8 of 320) vs. 7.3% (80 of 1095) with higher ratios (p < or = 0.01); bladder morbidity was 2.3% (7 of 305) and 5.8% (64 of 1110), respectively (p = 0.02). The incidence of Grade 2 and 3 bladder morbidity was 2.9% (10 of 336) when the dose rate was less than 0.80 Gy/h, in contrast to 6.1% (62 of 1010) with higher dose rates (p = 0.07). Rectal morbidity was 2% to 5% in Stage IB, regardless of dose rate to the rectum; in Stages IIA-B and III, morbidity was 5.2% (28 of 539) with a dose rate of 0.80 Gy or less and 10.7% (37 of 347) with higher dose rates (p < 0.01). Multivariate analysis showed that dose to the rectal point was the only factor influencing rectosigmoid sequelae, and dose to the bladder point affected bladder morbidity. CONCLUSIONS: Various dosimetric parameters correlate closely with the incidence of significant morbidity in patients treated with definitive irradiation for carcinoma of the uterine cervix. Careful dosimetry and special attention to related factors will reduce morbidity to the lowest possible level without compromising pelvic tumor control.

Brachytherapy↗
PubMed1999

Irradiation with or without misonidazole for patients with stages IIIB and IVA carcinoma of the cervix: final results of RTOG 80-05. Radiation Therapy Oncology Group.

PURPOSE: The purpose of this study was to evaluate tumor response, progression-free survival, local tumor control, patterns of relapse, and toxicity in patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix treated with irradiation or irradiation and misonidazole. This is a report of the final results of the study. METHODS: This study was a prospective randomized Phase III trial performed by the Radiation Therapy Oncology Group (RTOG). Between August 1980 and November 1984, 120 patients with Stages IIIb and IVa squamous cell carcinoma of the cervix were randomized to receive either standard irradiation or standard irradiation and misonidazole. Irradiation consisted of 46 Gy to the pelvis plus a 10 Gy parametrial boost followed by intracavitary brachytherapy or external irradiation boost to the primary tumor. Misonidazole was administered at 400 mg/m2 daily, 2-4 h before irradiation. Patients in the 2 treatment groups were evenly distributed by stage, Karnofsky Performance Status, and positive para-aortic lymph nodes. RESULTS: Sixty-one patients were treated with irradiation alone, and 59 patients received irradiation and misonidazole. Complete response in the pelvis occurred in 44 (75%) of those treated with irradiation and in 38 (64%) of those treated with irradiation and misonidazole. The progression-free survivals were 22% at 5 years for the control group, and 29% at 5 years for the misonidazole group. At the time of last follow-up, 18 patients in the control arm were free of disease, and in the experimental arm, 19 were free of disease. The patterns of failure for those treated with irradiation alone were local-only in 9 patients, distant-only in 8 patients, and local and distant in 11 patients. The patterns of failure for those receiving irradiation and misonidazole were local-only in 3 patients, distant-only in 8 patients, and local and distant in 8 patients. The maximum toxicity experienced per patient was grade 3 in 18%, grade 4 in 8%, and no grade 5 toxicity for those treated with irradiation alone compared to 8%, 2%, and 2%, respectively, for the experimental arm. CONCLUSION: There were no statistically significant differences in pelvic response, disease-free survivals, patterns of failure, or toxicity for the irradiation alone group or for the irradiation and misonidazole group as administered in this study for patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix.

Adult↗
PubMed1999

Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer.

BACKGROUND AND METHODS: We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group. RESULTS: Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P<0.001). The rates of both distant metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group. CONCLUSIONS: The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Factors affecting long-term outcome of irradiation in carcinoma of the vagina.

OBJECTIVE: This report evaluates prognostic and technical factors affecting outcome of patients with primary carcinoma of the vagina treated with definitive radiation therapy. METHODS AND MATERIALS: A retrospective analysis was performed on records of 212 patients with histologically confirmed carcinoma of the vagina treated with irradiation. RESULTS: Tumor stage was the most significant prognostic factor; actuarial 10-year disease-free survival was 94% for Stage 0 (20 patients), 80% for Stage I (59 patients), 55% for Stage IIA (63 patients), 35% for Stage IIB (34 patients), 38% for Stage III (20 patients), and 0% for Stage IV (15 patients). All in situ lesions except one were controlled with intracavitary therapy. Of the patients with Stage I disease, 86% showed no evidence of vaginal or pelvic recurrence; most of them received interstitial or intracavitary therapy or both, and the addition of external-beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) and IIB (parametrial involvement) 66% and 56% of the tumors, respectively, were controlled with a combination of brachytherapy and external-beam irradiation; 13 of 20 (65%) Stage III tumors were controlled in the pelvis. Four patients with Stage IV disease (27%) had no recurrence in the pelvis. The total incidence of distant metastases was 13% in Stage I, 30% in Stage IIA, 52% in Stage IIB, 50% in Stage III, and 47% in Stage IV. The dose of irradiation delivered to the primary tumor or the parametrial extension was of relative importance in achieving successful results. In patients with Stage I disease, brachytherapy alone achieved the same local tumor control (80-100%) as in patients receiving external pelvic irradiation (78-100%) as well. In Stage II and III there was a trend toward better tumor control (57-80%) with combined external irradiation and brachytherapy than with the latter alone (33-50%) (p = 0.42). The incidence of grade 2-3 complications (12%) correlated with the stage of the tumor and type of treatment given. CONCLUSION: Radiation therapy is an effective treatment for patients with vaginal carcinoma, particularly Stage I. More effective irradiation techniques, including optimization of dose distribution combining external irradiation and interstitial brachytherapy in tumors beyond Stage I, are necessary to enhance locoregional tumor control. The high incidence of distant metastases emphasizes the need for earlier diagnosis and effective systemic cytotoxic agents to improve survival in these patients.

Brachytherapy↗
PubMed1999

Surveillance of patients to detect recurrent thyroid carcinoma.

BACKGROUND: The purpose of this study was to evaluate the utility of surveillance with annual whole-body iodine-131 (131I) scintigraphy for patients with recurrent thyroid carcinoma. METHODS: The records of patients with thyroid carcinoma were reviewed. The 76 patients included in this study had undergone thyroidectomy and postoperative 131I therapy, and had at least 1 negative whole-body 131I scintigraphy 1 year after 131I therapy. There were 59 females and 17 males (age range, 12-74 years). Surgery consisted of a total thyroidectomy for 84% of patients and a subtotal thyroidectomy for 16%. 131I was administered within 1 month of thyroidectomy and annually thereafter until complete ablation of remaining thyroid tissue occurred. Annual follow-up diagnostic whole-body 131I scintigraphy was performed at Years 1 and 2, and then every 3-5 years. Some patients also had scintigraphy performed in Years 3, 4, and 5. RESULTS: Patients received 1-4 annual administrations of 131I (median, 1). The administered activity per treatment was 30-211 mCi, and the total activity administered that was necessary to achieve complete ablation of functioning thyroid tissue ranged from 30 to 514 mCi (median, 100 mCi). The relapse free survival at both 5 and 10 years was 88%. By definition, all of these patients had a negative 131I scintigraphy at 1 year after their last therapeutic 131I administration. Seven patients had a positive 131I scintigraphy 1 year after the first negative scintigraphy. Two other patients had positive 131I images after 2 consecutive negative annual 131I scintigraphic studies. The predictive value for relapse free survival of 1 negative diagnostic 131I study of these patients was 91% (+/- 0.02), and for 2 consecutive annual negative 131I studies the value was 97% (+/- 0.02); these results were significantly different (P = 0.0197). A stepwise logistic regression analysis was performed in an effort to identify risk factors for disease recurrence after complete ablation. None of the variables assessed--age, gender, tumor histology, tumor size, vascular invasion, capsular invasion, surgical margin status, or lymph node status--was predictive of recurrence after complete ablation. CONCLUSIONS: A single negative 131I scintigraphic study after complete ablation has a lower predictive value for relapse free survival than do two consecutive annual negative studies. Annual 131I imaging is recommended for surveillance until 2 consecutive annual negative studies are obtained, after which repeat imaging at 3-5 years appears to be satisfactory.

Adenocarcinoma, Follicular↗