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Biomedical subjects

Perry W Grigsby

Publications and source records attributed to Perry W Grigsby.

At least 19 recordsLinked to original sources

Adaptive brachytherapy treatment planning for cervical cancer using FDG-PET.

PURPOSE: A dosimetric study was conducted to compare intracavitary brachytherapy using both a conventional and a custom loading intended to cover a positron emission tomography (PET)-defined tumor volume in patients with cervix cancer. METHODS AND MATERIALS: Eleven patients who underwent an [(18)F]-fluoro-deoxy-D-glucose (FDG)-PET in conjunction with their first, middle, or last brachytherapy treatment were included in this prospective study. A standard plan that delivers 6.5 Gy to point A under ideal conditions was compared with an optimized plan designed to conform the 6.5-Gy isodose surface to the PET defined volume. RESULTS: A total of 31 intracavitary brachytherapy treatments in conjunction with an FDG-PET were performed. The percent coverage of the target isodose surface for the first implant with and without optimization was 73% and 68% (p = 0.21). The percent coverage of the target isodose surface for the mid/final implant was 83% and 70% (p = 0.02), respectively. The dose to point A was higher with the optimized plans for both the first implant (p = 0.02) and the mid/last implants (p = 0.008). The dose to 2 cm(3) and 5 cm(3) of both the bladder and rectum were not significantly different. CONCLUSIONS: FDG-PET based treatment planning allowed for improved dose coverage of the tumor without significantly increasing the dose to the bladder and rectum.

Adult↗

Comparison of high-dose-rate and low-dose-rate brachytherapy in the treatment of endometrial carcinoma.

PURPOSE: To compare the outcomes for endometrial carcinoma patients treated with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. METHODS AND MATERIALS: This study included 1,179 patients divided into LDR (1,004) and HDR groups (175). Patients with International Federation of Gynecology and Obstetrics (FIGO) surgical Stages I-III were included. All patients were treated with postoperative irradiation. In the LDR group, the postoperative dose applied to the vaginal cuff was 60-70 Gy surface doses to the vaginal mucosa. The HDR brachytherapy prescription was 6 fractions of 2 Gy each to a depth of 0.5 cm from the surface of the vaginal mucosa. Overall survival, disease-free survival, local control, and complications were endpoints. RESULTS: For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the LDR group were 70%, 69%, and 81%, respectively. For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the HDR group were 68%, 62%, and 78%, respectively. There were no significant differences in early or late Grade III and IV complications in the HDR or LDR groups. CONCLUSION: Survival outcomes, pelvic tumor control, and Grade III and IV complications were not significantly different in the LDR brachytherapy group compared with the HDR group.

Adolescent↗

Outcomes in 24 selected patients with stage IVB cervical cancer and excellent performance status treated with radiotherapy and chemotherapy.

PURPOSE: We sought to review outcomes in patients with stage IVB carcinoma of the cervix treated with irradiation in combination with chemotherapy. MATERIALS AND METHODS: We report outcomes of 24 consecutive patients with good performance status treated from 1998 to 2005. Most of these patients underwent concurrent irradiation with platinum-based chemotherapy. Some patients received subsequent systemic chemotherapy. RESULTS: All patients underwent external beam radiotherapy; 7 patients (29%) had additional high-dose-rate and 12 (50%) low-dose-rate brachytherapy. Two patients (8%) received an IMRT boost instead of brachytherapy. The mean dose to point A was variable (73.9 +/- 19.2 Gy). Twenty patients (83%) received radio-sensitizing platinum-based chemotherapy, and the remaining had radiotherapy alone. Seven patients (29%) had further combination chemotherapy. Therapy was well tolerated. The overall survival was 44% at 36 months and 22% at 5 years. CONCLUSION: Patients with stage IVB cervical cancer have mostly been treated with palliative intent. With the advent of concurrent chemoradiation, we have treated many of these cases with aggressive combination therapy. In this series, the use of radiotherapy and multiagent chemotherapy in patients with stage IVB cervical carcinoma and good performance status was well tolerated and resulted in higher survival rates than previously reported.

Adult↗

Contralateral papillary thyroid cancer at completion thyroidectomy has no impact on recurrence or survival after radioiodine treatment.

BACKGROUND: This study investigated the rate of contralateral papillary thyroid cancer (PTC) in low-risk PTC patients who had completion thyroidectomy, and were referred for radioactive iodine (RAI) therapy. The study sought predictors of contralateral disease and examined the impact of contralateral disease in RAI-treated patients. METHODS: We reviewed 20 years of data from a prospective registry for 150 patients with PTC. These patients had undergone thyroid lobectomy, followed by completion thyroidectomy, and had been referred for RAI. RESULTS: Of the 150 patients, 41% had PTC in the contralateral lobe. There was no difference in the rate of contralateral disease in low-risk patients (age <45 years, T1 tumors, lymph node-negative) compared with the remainder. There were no significant differences between patients with or without contralateral disease with respect to primary tumor size, mean age, time to completion thyroidectomy, or metastatic lymph node disease. Logistic regression analyses showed no histologic parameters that correlated with contralateral disease. There were no recurrence or survival differences in patients with or without contralateral disease after resection and RAI. CONCLUSIONS: The prevalence of tumor in the contralateral lobe of low-risk patients with PTC is significant and warrants consideration for completion thyroidectomy and radioiodine treatment. Our results, however, suggest that contralateral disease does not have an impact on recurrence or survival after treatment.

Adolescent↗

Lymph node metastases in differentiated thyroid cancer under 2 cm.

BACKGROUND: The goal of this study was to evaluate the presence of lymph node metastasis in patients with T1 differentiated thyroid cancer (DTC) and determine prognostic significance for tumor recurrence and cancer-related death. METHODS: From a prospective tumor registry, we reviewed data from 551 patients with DTC who underwent total or subtotal thyroidectomy and who had primary tumor size </=2 cm. Patients received standard radioactive iodine ablation. RESULTS: The proportion of patients with lymph node metastasis was 45%. This percentage remained the same in a comparison of tumors from 0 to 1 cm with tumors from 1 to 2 cm. Logistic regression analyses did not identify primary tumor size as a predictor of lymph node metastasis, but did show that histologic vascular invasion and soft tissue invasion correlated with positive lymph nodes. Multifocal disease approached significance. Actuarial estimates for first recurrence displayed a significant difference in patients who had positive cervical lymph nodes versus negative nodes: 56% versus 71% disease-free at 20 years. There was no difference in cancer-related death. CONCLUSIONS: In T1 DTC, lymph node metastasis does not correlate with tumor size but does correlate with vascular/soft tissue invasion. Patients with positive lymph nodes have a higher recurrence risk, but no significant increase in death.

Adolescent↗

A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: implications for radiation dose escalation in carcinoma of the pancreas.

PURPOSE: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. RESULTS: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. CONCLUSION: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel.

Dose-Response Relationship, Radiation↗

Cisplatin chemotherapy (without erythropoietin) and risk of life-threatening thromboembolic events in carcinoma of the uterine cervix: the tip of the iceberg? A review of the literature.

BACKGROUND: The risk of severe cardiovascular toxicity, specifically thromboembolic events (TE), in patients with cervical cancer receiving concurrent irradiation and cisplatin chemotherapy is reported to be less than 1% in several large prospective trials. However, the anecdotal risk appears to be far higher. RESULTS AND DISCUSSION: A review of several prospective trials demonstrates no treatment related grade 4 cardiovascular toxicities and only two grade 5 toxicities in 1424 (0.1%) collective patients. A recent publication and our own unpublished experience finds 6 of 128 (4.7%) patients developed grade 4 to 5 cardiovascular (thrombosis/embolism) toxicity. The difference in incidence of severe or life threatening cardiovascular toxicity of 0.1 versus 4.7% is highly statistically significant (p < 0.00001.) CONCLUSION: This dramatic difference in incidence of cardiovascular toxicity raises the possibility that cardiovascular toxicities were inadequately reported on the listed prospective trials. For those patients enrolled in prospective trials, we suggest that thromboses should be diligently documented and reported. Only after the true incidence of thromboses is established can we implement appropriate levels of early screening and intervention that may prevent life threatening complications.

Antineoplastic Agents↗

Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer.

OBJECTIVE: To report the utility of the monoclonal, anti-vascular endothelial growth factor antibody bevacizumab in combination with cytotoxic chemotherapy for women with recurrent cervical cancer. METHODS: A retrospective analysis of women with recurrent cervical cancer treated with bevacizumab combination therapy was performed. RESULTS: Six patients were identified. The patients had a median of 3 prior regimens. All of the patients had multisite, metastatic disease. The combination regimen included IV 5-fluorouracil in 5 (83%) patients and capecitabine in one (17%) subject. Treatment was well tolerated. Grade 4 toxicity occurred in one patient who developed neutropenic sepsis. Clinical benefit (CR, PR, or SD) was noted in 67% of the subjects. This included 1 (17%) complete response, 1 (17%) partial response and two (33%) patients with stable disease. The median time to progression for the four women who demonstrated clinical benefit was 4.3 months. CONCLUSIONS: Combination bevacizumab is well tolerated and displayed encouraging anti-tumor activity in heavily pretreated recurrent cervical cancer.

Adult↗

FDG-PET/CT in the evaluation of anal carcinoma.

PURPOSE: Surgical staging and treatment of anal carcinoma has been replaced by noninvasive staging studies and combined modality therapy. In this study, we compare computed tomography (CT) and physical examination to [(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the staging of carcinoma of the anal canal, with special emphasis on determination of spread to inguinal lymph nodes. METHODS AND MATERIALS: Between July 2003 and July 2005, 41 consecutive patients with biopsy-proved anal carcinoma underwent a complete staging evaluation including physical examination, CT, and 2-FDG-PET/CT. Patients ranged in age from 30 to 89 years. Nine men were HIV-positive. Treatment was with standard Nigro regimen. RESULTS: [(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) detected 91% of nonexcised primary tumors, whereas CT visualized 59%. FDG-PET/CT detected abnormal uptake in pelvic nodes of 5 patients with normal pelvic CT scans. FDG-PET/CT detected abnormal nodes in 20% of groins that were normal by CT, and in 23% without abnormality on physical examination. Furthermore, 17% of groins negative by both CT and physical examination showed abnormal uptake on FDG-PET/CT. HIV-positive patients had an increased frequency of PET-positive lymph nodes. CONCLUSION: [(18)F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography detects the primary tumor more often than CT. FDG-PET/CT detects substantially more abnormal inguinal lymph nodes than are identified by standard clinical staging with CT and physical examination.

Adult↗

FDG-PET imaging for the assessment of physiologic volume response during radiotherapy in cervix cancer.

PURPOSE: To evaluate the physiologic tumor volume response during treatment in cervical cancer using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). PATIENTS AND METHODS: This was a prospective study of 32 patients. Physiologic tumor volume in cubic centimeters was determined from the FDG-PET images using the 40% threshold method. RESULTS: The mean pretreatment tumor volume was 102 cm3. The mean volume by clinical Stages I, II, and III were 54, 79, and 176 cm3, respectively. After 19.8 Gy external irradiation to the pelvis, the reduction in tumor volume was 29% (72 cm3). An additional 13 Gy from high-dose-rate (HDR) brachytherapy reduced the mean volume to 15.4 cm3, and this was subsequently reduced to 8.6 cm3 with 13 Gy additional HDR brachytherapy (26 Gy, HDR). Four patients had physiologic FDG uptake in the cervix at 3 months after the completion of therapy. The mean time to the 50% reduction in physiologic tumor volume was 19.9 days and after combined external irradiation and HDR to 24.9 Gy. CONCLUSION: These results indicate that physiologic tumor volume determination by FDG-PET is feasible and that a 50% physiologic tumor volume reduction occurs within 20 days of starting therapy.

Adenocarcinoma, Clear Cell↗

FDG-PET in carcinoma of the uterine cervix with endometrial extension.

BACKGROUND: The authors wished to determine whether pretreatment pathologic evidence of endometrial invasion correlated with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings and outcomes in patients with carcinoma of the uterine cervix. METHODS: Pretreatment whole body FDG-PET was performed in 58 patients with cervical carcinoma who also underwent pathologic evaluation of the endometrium by biopsy or dilation and curettage. FDG-PET lymph node status, disease free survival, and overall survival were evaluated. RESULTS: Thirty seven (64%) patients had pathologic evidence of endometrial invasion. Pelvic lymph node metastases were three times more frequent in patients with evidence of endometrial invasion compared with those without endometrial invasion (70% vs. 23%, P < 0.001). Patients with endometrial invasion also had a significantly increased risk of paraaortic and supraclavicular lymph node metastases at presentation (30% vs. 0% P = 0.006). Endometrial invasion was associated with a decreased 2-year disease-free survival (78% vs. 58%, P = 0.046) and overall survival (92% vs. 65%, P = 0.047). CONCLUSIONS: Endometrial extension in cervical cancer correlated strongly with risk of FDG-PET detected lymph node metastases in this study's population and was associated with a poor prognosis.

Adenocarcinoma↗

Progress toward a microradiation therapy small animal conformal irradiator.

Microradiation therapy (microRT) systems are being designed to provide conformal radiation therapy to small animals enabling quantitative radiation response evaluation. We used a Monte Carlo approach to estimate the radiation dose distributions from proposed blueprints and developed a beam model to aid in the microRT system design process. This process was applied to a prototype irradiator that uses a small (3 mm long and 3 mm in diameter), cylindrical, high-activity 192Ir source delivering the radiation beam using custom-fabricated tungsten collimators. The BEAMnrc Monte Carlo code was used to simulate dose distributions from these prototype collimators. Simulations were performed at three source-to-surface distances (50, 60, and 70 mm), and with five circular field sizes (5, 7.5, 10, 12.5, and 15 mm). A dose to a 50 X 50 X 50 mm3 water phantom with 1 X 1 X 1 mm3 voxel spacing was computed. A multiparameter dose calculation algorithm was developed to efficiently and accurately calculate doses for treatment planning exercises. The parametrization was selected so that the parameters varied smoothly as a function of depth, source-to-surface distance, and field size, allowing interpolation for geometries that were not simulated using the Monte Carlo simulation. Direct comparison of the model with the Monte Carlo simulations showed that the variations were within 5% error for field sizes larger than 10 mm, and up to 10% for smaller field sizes.

Animals↗

Preoperative lymph node staging of early-stage cervical carcinoma by [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography.

BACKGROUND: Increasing evidence has documented the value of positron emission tomography (PET) in oncology, but only limited data are available comparing PET findings with the pathologic status of regional lymph nodes in patients with cervical carcinoma. The objective of this study was to determine the sensitivity and specificity of PET in detecting lymph node metastasis in women with early-stage cervical carcinoma. METHODS: The authors performed a retrospective review of all patients with Stage IA-IIA cervical carcinoma who underwent PET before surgery from 1999 to 2004. The status of the regional lymph nodes was correlated with lymph node pathology. RESULTS: Fifty-nine patients were identified. Pelvic lymph node metastases were present in 32% of the patients and were detected by PET with a sensitivity of 53%, a specificity of 90%, a positive predictive value (PPV) of 71%, and a negative predictive value (NPV) of 80%. Paraaortic lymph node disease was present in 9% of patients and was detected by PET with a sensitivity of 25%, a specificity 98%, a PPV of 50%, and an NPV of 93%. The mean size of the tumor deposits was larger in the PET-positive pelvic nodes (15.2 mm; range, 2-35 mm) than in the PET-negative lymph nodes (7.3 mm; range, 0.3-20 mm; P = 0.002). Computed tomography (CT) scans were obtained before surgery in 42 patients. The combined sensitivity of PET and CT in these patients was 75%. PET alone detected 9 (36%) of the positive lymph node groups, whereas CT alone detected 3 (12%) of the positive lymph node groups. Neither PET nor CT detected the positive lymph node groups in 8 patients (32%). CONCLUSIONS: Pathologic validation of PET imaging demonstrated a low sensitivity and a high specificity for PET in patients with early-stage cervical carcinoma.

Female↗

F-18 fluorodeoxyglucose uptake in primary cervical cancer as an indicator of prognosis after radiation therapy.

PURPOSE: We evaluated the prognostic significance of tumor metabolic activity on pretreatment positron emission tomography using the glucose analog F-18 fluorodeoxyglucose (FDG-PET) in patients with carcinoma of the cervix undergoing radiotherapy with or without concurrent chemotherapy. METHODS: We studied 96 consecutive patients who underwent FDG-PET prior to initiation of radiotherapy with or without concurrent chemotherapy for carcinoma of the cervix. Pretreatment FDG uptake of the primary tumor was assessed with the semiquantitative standardized uptake value (SUV) and correlated with disease-free and overall survival. Survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed with the logistic likelihood ratio test and the Cox proportional hazards model, respectively. RESULTS.: Five-year disease-free survivals in patients with maximal SUV <10.2 and > or =10.2 were 71% and 52% (P = 0.0289) respectively, while overall survivals were 72% and 69% (P = 0.4), respectively. On multivariate analysis, lymph node metastasis on FDG-PET was found to be predictive of disease-free survival (P < 0.0001). Both the SUV for FDG and FIGO Stage I disease were found to be marginally predictive of disease-free survival (P = 0.055 and P = 0.058, respectively). CONCLUSIONS: FDG uptake within primary cervical cancer, as measured by SUV, is predictive of disease-free survival in patients undergoing radiotherapy for cervical cancer. High FDG uptake may be useful in identifying patients who may require more aggressive initial therapy.

Adult↗

Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer.

PURPOSE: The aim of our study was to assess prognostic factors and overall survival after salvage radiotherapy for patients who had endometrial carcinoma and who experienced an isolated vaginal recurrence. METHODS AND MATERIALS: We reviewed the records of 50 patients treated at our institution between 1967 and 2003 for an isolated vaginal recurrence of endometrial carcinoma. Initial treatment for endometrial carcinoma was definitive surgery in 49 patients and definitive radiotherapy in 1 patient. The median time from initial diagnosis of endometrial carcinoma to recurrence was 25 months (range, 4-179 months). Three patients (6%) received external-beam radiotherapy alone, 8 patients (16%) received brachytherapy only, and 39 patients (78%) received combined external-beam radiation therapy and brachytherapy. Median dose of radiation to the recurrence was 60 Gy (range, 16-85 Gy). Overall survival was calculated by the Kaplan-Meier method. Endpoints were measured from the date of diagnosis of the vaginal recurrence. Median follow-up of survivors after recurrence was 53 months (range, 8-159 months). RESULTS: The 5-year and 10-year disease-free and overall survivals were 68% and 55%, and 53% and 40%, respectively. On multivariate analysis, age (p = 0.0242), Grade 1 or 2 vs. Grade 3 tumor (p = 0.002), and size of recurrence (p < 0.001) were significant predictors of overall survival. All patients who had Grade 3 disease were dead by 3.6 years from the time of recurrence. Five patients experienced a Grade 3 or 4 complication. CONCLUSIONS: Patients treated with radiotherapy for an isolated vaginal recurrence can be cured in over 50% the cases. Radiotherapy is well tolerated, with a low risk of complications. Factors predictive of overall survival include tumor grade, patient age at recurrence, and tumor size.

Adult↗

Sequential FDG-PET brachytherapy treatment planning in carcinoma of the cervix.

PURPOSE: To evaluate the utility of sequential (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brachytherapy treatment planning in patients with carcinoma of the cervix. METHODS AND MATERIALS: Twenty-four patients with carcinoma of the cervix were included in this prospective study. The clinical stage of their disease was Ib (7), IIa (1), IIb (7), and IIIb (9). Patients were treated with irradiation and brachytherapy, with the majority receiving concurrent weekly cisplatin chemotherapy. Patients underwent diagnostic FDG-PET imaging before treatment, sequential FDG-PET brachytherapy imaging during treatment, and diagnostic FDG-PET 3 months after treatment completion. Delineation of the gross tumor volume, bladder, and rectum was performed for all scans using a commercially available treatment-planning system. Actual treatment delivery was based on two-dimensional orthogonal planning. RESULTS: The mean gross tumor volume and percent coverage by the target isodose surface for the initial, mid, and last implant were 37 cm3, 17 cm3, and 10 cm3 and 68%, 76%, and 79%, respectively. Nine of 11 patients were found to have continued decrease in tumor volume as measured by FDG-PET, with 3 patients having complete regression of their tumor before treatment was completed. The maximal bladder and rectal doses obtained from three-dimensional dose-volume histograms were significantly higher than the International Commission on Radiation Units and Measurements Report 38 bladder and rectal points obtained by two-dimensional treatment-planning. CONCLUSIONS: Sequential FDG-PET brachytherapy imaging identifies the tumor response in individual patients, potentially making patient-specific brachytherapy treatment planning possible.

Adult↗

FDG-PET evaluation of vaginal carcinoma.

PURPOSE: To compare the results of CT and positron emission tomography (PET) and F-18 fluorodeoxyglucose (FDG) in the detection of the primary tumor and lymph node metastases in carcinoma of the vagina. METHODS AND MATERIALS: This was a prospective registry study of 23 consecutive patients with carcinoma of the vagina, in which we respectively compared the results of CT and whole-body FDG-PET. The tumor was clinical Stage II in 16 patients, Stage III in 6, and Stage IVa in 1 patient. The primary tumor ranged in size from 2 to 10 cm (mean 4.9), and 4 patients had palpable groin lymph nodes. All patients were treated with external beam radiotherapy and brachytherapy, 14 received concurrent chemotherapy, and 2 underwent primary tumor excision before the imaging evaluation. The median follow-up was 21 months in those patients alive without disease. Survival was estimated by the Kaplan-Meier method. RESULTS: Of the 21 patients with an intact primary tumor, CT visualized it in 9 (43%). CT also demonstrated abnormally enlarged groin lymph nodes in 3 patients and both groin and pelvic lymph nodes in 1 patient (4 of 23, 17%). FDG-PET identified abnormal uptake in all 21 intact primary tumors (100%). Abnormal uptake was found in the groin lymph nodes in 4 patients, pelvic lymph nodes in 2, and both groin and pelvic lymph nodes in 2 patients (8 of 23, 35%). The 3-year progression-free and overall survival estimate was 73% and 68%, respectively. CONCLUSION: The results of this study have demonstrated that FDG-PET detects the primary tumor and abnormal lymph nodes more often than does CT.

Carcinoma↗