Biomedical subjects

Carlos A Perez

Publications and source records attributed to Carlos A Perez.

At least 19 recordsLinked to original sources

PubMed2004

Carcinoma of paranasal sinuses: long-term outcomes with radiotherapy.

PURPOSE: To assess the clinical features, prognostic factors, results, and complications of treatment of carcinomas of the paranasal sinus. METHODS AND MATERIALS: The records of 106 patients (72 men and 34 women) with paranasal sinus carcinoma treated with curative intent at Washington University between January 1960 and August 1998 were analyzed. Patient age ranged from 29 to 91 years (median, 64 years). Most tumors originated in the maxillary (76%) or ethmoid (18%) sinus. Most tumors were locally advanced at presentation. All patients underwent radiotherapy (RT), combined with surgery in 65%; 2% received chemotherapy. RESULTS: Follow-up ranged from 1.7 months to 24 years (median 5 years). The 5-year local tumor control, locoregional tumor control, disease-free survival (DFS), and overall survival rate was 58%, 39%, 33%, and 27%, respectively. A statistically significant improvement in DFS was noted with the addition of surgical resection to RT (35% vs. 29%, p = 0.05). Nodal status at presentation emerged as a statistically significant predictor for locoregional tumor control and DFS in multivariate analysis. Distant metastases occurred in 29% of patients. CONCLUSION: This review of a large, single-institution experience of paranasal sinus carcinoma patients who underwent RT showed that locoregional tumor progression and recurrence remain predominant patterns of failure despite aggressive local treatment with combined surgery and RT. DFS improved slightly with combined modality treatment. The overall survival rates remained suboptimal, suggesting a need for more accurate determination of tumor extent, as well as more effective locoregional and systemic therapies.

Adenocarcinoma↗

PubMed2004

Toxicity after three-dimensional radiotherapy for prostate cancer with RTOG 9406 dose level IV.

PURPOSE: This is the first report of the toxicity outcomes using dose level IV (74 Gy) on Radiation Therapy Oncology Group (RTOG) study 9406 for Stage T1-T2 prostate adenocarcinoma. METHODS AND MATERIALS: A total of 262 patients were entered in this cooperative group, Phase I-II, dose-escalation trial of three-dimensional conformal radiotherapy for localized prostate carcinoma treated to a dose of 74 Gy (Level IV); 256 patients were analyzable for toxicity. A minimal dose of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion on the basis of the Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of >/=15%. Patients in Group 1 were prescribed 74 Gy to a prostate PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 74 Gy. PTV margins between 5 and 10 mm were required. Elective pelvic radiotherapy was not used. The frequency of late effects of Grade 3 or greater was compared with that for a similar group of patients treated in RTOG studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 206 patients treated to dose level II (73.8 Gy in 1.8-Gy fractions) to see whether the fraction size affected toxicity. RESULTS: The average months at risk for late Grade 3+ toxicity after therapy completion were 28.9 and 23.9 months for Group 1 and 2, respectively. Acute toxicity at dose level IV (74 Gy) was remarkably low, with Grade 3 acute effects reported in only 1% of Group 1 and 3% of Group 2 patients. No Grade 4 or 5 acute toxicities were reported. Late toxicity continued to be low compared with RTOG historical controls. One patient in Group 1 and 4 patients in Group 2 experienced Grade 3 bladder toxicity. Two patients in Group 2 experienced Grade 3 bowel toxicity. No Grade 4 or 5 late effects were reported. The rate of late Grade 2 toxicity (any type) was 23% and 16% in Group 1 and 2, respectively. The observed rate of Grade 3 or greater late effects for Group 1 (1 case) was significantly lower (p <0.0001) than the 18.5 cases that would have been expected from the historical control data. The observed rate for Group 2 (6 cases) was also significantly lower (p = 0.0009) than the 21.3 cases expected. No statistically significant difference was noted in the rate of acute or late toxicity in patients who were treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. Patients treated with the larger 2.0-Gy fractions tended to have more Grade 3 or greater toxicity than patients treated with 1.8-Gy fractions (2% vs. 1%, p = 0.09). The results after the longer follow-up with dose level II suggest these differences may increase with additional follow-up. CONCLUSION: Tolerance to three-dimensional conformal radiotherapy with 74 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size requires additional follow-up.

Adenocarcinoma↗

PubMed2004

Implementing biologic target volumes in radiation treatment planning for non-small cell lung cancer.

18F-FDG PET offers the radiation oncology community the ability to incorporate biologic information into radiation therapy targets. To date, most of the work in this arena has involved patients with non-small cell lung cancer (NSCLC). The literature suggests that biologic targeting with PET alters the radiation treatment volume significantly in 30%-60% of NSCLC patients for whom definitive therapy is planned. This is mostly the result of the incorporation of regional nodes with 18F-FDG avidity that were previously judged to be uninvolved by CT criteria. The development of the integrated PET/CT scanner is a valuable tool that improves diagnostic accuracy for staging this disease and will increase the accessibility of PET for radiation treatment planning. Its implementation into radiation treatment planning requires strong collaboration between radiation oncologists and nuclear physicians. In this report, we will review the literature on PET-based radiation treatment planning, its potential benefits, and future challenges.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Radiotherapeutic approaches to metastatic disease.

Bone metastases in patients with prostate cancer are common. Prostate cancer patients also have a relatively long survival. Palliative radiation can provide effective symptom control in many clinical settings. This article focuses on the management of bone pain and its complications (pathological fractures and spinal cord compression) with radiation treatment.

Bone Neoplasms↗

PubMed2003

Elective nodal failures are uncommon in medically inoperable patients with Stage I non-small-cell lung carcinoma treated with limited radiotherapy fields.

PURPOSE: To review the outcome for 56 Stage I non-small-cell lung cancer treated definitively with three-dimensional conformal radiotherapy (3D-CRT) and to investigate the value of elective nodal irradiation in this patient population. METHODS AND MATERIALS: Between 1992 and 2001, 56 patients were treated with 3D-CRT for inoperable Stage I histologically confirmed non-small-cell lung cancer; 31 with T1N0 and 25 with T2N0 disease. All patients were treated with 3D-CRT to a median isocenter dose of 70 Gy (range 59.94-83.85) given in daily doses of 1.8 or 2 Gy. Prognostic factors were analyzed with respect to their impact on overall survival. Twenty-two patients received radiotherapy (RT) directed to elective regional lymphatics to doses of 45-50 Gy. The remaining 33 patients were treated to limited fields confined to the primary lung cancer with a margin. The patterns of failure were reviewed. RESULTS: The median follow-up was 20 months (range 6 months to 6 years). The actuarial local control rate was 88%, 69%, and 63%, at 1, 2, and 3 years, respectively. The actuarial cause-specific survival rate was 82%, 67%, and 51% at 1, 2, and 3 years, respectively. The actuarial overall survival rate was 73%, 51%, and 34% at 1, 2, and 3 years, respectively. The actuarial metastasis-free survival rate was 90%, 85%, and 81% at 1, 2, and 3 years, respectively. The RT dose was the only factor predictive of overall survival in our analysis. No statistically significant difference was noted in cause-specific or overall survival according to whether patients received elective nodal irradiation. Two of 33 patients treated with limited fields had regional nodal failure. CONCLUSION: Many patients with medically inoperable Stage I lung cancer die of intercurrent causes. The omission of the elective nodal regions from the RT portals did not compromise either the cause-specific or overall survival rate. Elective nodal failures were uncommon in the group treated with limited RT fields. A radiation dose 70 Gy was predictive of better survival in our population. We await the results of prospective trials evaluating high-dose RT in patients treated with RT alone for Stage I lung cancer.

Aged↗

PubMed2003

Preliminary evaluation of low-grade toxicity with conformal radiation therapy for prostate cancer on RTOG 9406 dose levels I and II.

PURPOSE: To evaluate the rates of low-grade late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. MATERIALS AND METHODS: Between August 1994 and September 1999, 424 patients were entered on this dose escalation trial of three-dimensional conformal radiation therapy (3D-CRT) for localized adenocarcinoma of the prostate at doses of 68.4 Gy (level I) and 73.8 Gy (level II). We have previously reported Grade 3 or greater late toxicity of patients treated on the first two dose levels of this trial. This analysis examines the distribution of all late toxicities in these patients. All radiation prescriptions were a minimum dose to a planning target volume (PTV). Patients were stratified according to clinical stage and risk of seminal vesicle invasion (SVI) based upon Gleason score and presenting prostate-specific antigen. Group 1 includes patients with T1,2 disease with SVI risk < 15%, and Group 2 includes patients with T1,2 disease with SVI risk > 15%. Group 3 patients had T3 disease. Average months at risk after completion of therapy ranged from 21.4 to 40.1 months for patients treated at dose level I and 10.0 to 34.2 months for patients at dose level II. The frequency of all grades of late effects was compared with a similar group of patients treated in RTOG studies 7506 and 7706 with adjustments made for the interval from completion of therapy. The RTOG toxicity scoring scales for late effects were used for grading. RESULTS: The rate of Grade 3 or greater late toxicity continues to be low compared with RTOG historical controls. No Grade 4 or 5 late sequelae were reported in any of the 393 evaluable patients during the period of observation. The frequency of patients free of any complications was lower in RTOG 9406 than in historical controls. In the 73 Group 1 patients treated on dose level 1, there were 24 patients without sequelae compared with an expected rate of 39.7 (p = 0.013), and in 80 Group 3 patients at dose level II there were 24 patients without sequelae when 56.2 were expected (p < 0.0001). Other groups treated at these dose levels demonstrated a nonsignificant reduction in the rate of patients free of any side effects. These data suggest that the reduction in high-grade morbidity may be related to a shift of complications to lower grades. CONCLUSIONS: Morbidity of 3D-CRT in the treatment of prostate cancer is low. It is important to continue to closely examine late effects in patients treated in RTOG 9406. The primary objective of dose escalation without an increase rate of >/= Grade 3 sequelae has been achieved. However, the reduction in Grade 3 complications may have resulted in a higher incidence of Grade 1 or 2 late effects. Because Grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.

Adenocarcinoma↗

PubMed2003

The impact of regional nodal radiotherapy (dose/volume) on regional progression and survival in unresectable non-small cell lung cancer: an analysis of RTOG data.

PURPOSE: To evaluate in-field progression and survival of patients with unresectable non-small cell lung cancer (NSCLC) in relation to adequacy of coverage of thoracic regional nodal areas in the radiotherapy volume. MATERIALS AND METHODS: A total of 1705 patients from four large RTOG trials (78-11, 79-17, 83-11 and 84-07) were analyzed for this purpose. For each of these trials, the dose delivered to nodal regions was recorded and an assessment of adequacy of field borders was made. Each nodal site was assessed for progression, defined as in-field or out-of-field. In patients who had adequate borders on nodal regions, the results were analyzed according to the dose delivered. RESULTS: The majority (74%) of patients were between the age of 55-75. Forty-six percent of the patients had KPS of 60-80 and 52% had KPS of 90-100. Sixty percent of patients had a weight loss of less than 5% in the 6 months prior to diagnosis. Deviations from the protocol in field borders (borders not per protocol) were most frequent for the contralateral hilum (25.2%) and least frequent in the ipsilateral hilum (6.3%). The adequacy of ipsilateral hilar coverage was important for preventing the in-field progression (11.6 vs. 22% for adequately vs. inadequately covered ipsilateral hilum, respectively, P=0.01), however, did not influence the 2-year-survival (35 vs. 37%) or median survival (1.3 vs. 1.1 year). Neither the in-field progression nor the 2-year-survival were affected by adequacy of nodal coverage in the mediastinum, ipsilateral supraclavicular area and contralateral hilum, even when different doses were analyzed. CONCLUSION: These data suggest that elective irradiation of mediastinal, contralateral hilar and supraclavicular lymph nodes may not be necessary in the treatment of unresectable NSCLC.

Aged↗

PubMed2003

Radiation therapy after radical prostatectomy: a review of the issues and options.

The role of postoperative radiation therapy after radical prostatectomy is controversial. Radiation can be delivered as an adjuvant therapy in the immediate postoperative period for high-risk patients or as salvage therapy in the setting of a rising prostate-specific antigen. There are important issues that must be addressed when considering radiation therapy after prior prostatectomy. One issue is the determination of whether a patient has local disease amenable to salvage pelvic radiation or whether the patient has occult metastatic disease. In addition, the radiation oncologist must decide if an acceptable dose of radiation therapy can be administered safely to the prostate bed. There are no published randomized clinical trials on the topic of postprostatectomy radiation therapy, although several have completed accrual or are in progress. Based on the available literature, postoperative radiation is a safe option in the patient at high risk for local recurrence based on adverse pathology or clinical features (eg, extensive extracapsular disease, positive margins, high volume Gleason score >7, and so on). Administration of an adequate dose of prostate bed radiation (ie, >64 Gy) in men with these adverse prognostic features appears to effectively reduce prostate-specific antigen (PSA) recurrence rates. The protracted natural history of prostate cancer requires longer follow-up to determine if survival will be ultimately affected by adjuvant or salvage radiation therapy. Some urologists have advised a "wait and watch policy" for high-risk postprostatectomy patients. Administration of radiation therapy is done only if and when the PSA rises. However, data suggest this approach may have limited durability in high-risk prostate cancer and could reduce the likelihood of prolonged progression-free survival. This review summarizes published retrospective and prospective data to guide decision making in selecting appropriate candidates for postprostatectomy radiation therapy.

Clinical Trials as Topic↗

PubMed2003

Radiation therapy for increasing prostate-specific antigen levels after radical prostatectomy.

Herein we present data on outcomes in patients with increasing prostate-specific antigen (PSA) levels treated with irradiation to the pelvis and/or prostatic bed after radical prostatectomy. Between 1988 and 1998, 92 patients who presented with increasing PSA levels after radical prostatectomy were treated with irradiation, 29 to the pelvis and prostatic bed and 63 to the prostatic bed only. The mean follow-up was 4 years for the 3D-CRT group and 6.5 years for the standard radiation therapy group. Criterion for biochemical failure was an increase in post irradiation PSA level on > or = 1 consecutive measurement. Patients were classified into 3 risk groups based on prognostic factors: pathologic tumor extent and stage, Gleason score, and PSA levels before irradiation. Acute and late morbidity was quantitatively evaluated in all patients. There was a close correlation between the preirradiation PSA level and the probability of 4-year biochemical failure-free survival (75% with PSA levels < or = 1 ng/mL, 30% with PSA levels of 1.1-2 ng/mL, and 20% with PSA levels > 2 ng/mL; P = 0.05). The 4-year chemical failure rate was 20% in the low/intermediate-risk group and 65% in the high-risk group (P = 0.36). In 20 patients in the low-PSA group (< or =1 ng/mL) receiving doses > 62 Gy, no biochemical failures have been detected in comparison to a 70% failure rate at 4 years in patients treated with lower doses (P = 0.15). In the higher-PSA groups, no impact of irradiation dose on outcome was noted (40%-60% incidence of failure at 3 years). Pelvic irradiation was associated with a trend toward decreased biochemical failure rate in the low-PSA group (70% vs. 0% at 4 years; P = 0.35), but not in the high-PSA group. Only 1 patient (1.5%) experienced clinical local recurrence in the prostatic bed and 2 patients (1.8%) had distant metastases. Treatment has been very well tolerated, with only 3 patients in the arc-rotation group experiencing grade 2 treatment toxicity. Prostate bed irradiation is an effective treatment in a significant proportion of patients who present with a biochemical failure after radical prostatectomy.

Acute Disease↗

PubMed2002

Interim report of toxicity from 3D conformal radiation therapy (3D-CRT) for prostate cancer on 3DOG/RTOG 9406, level III (79.2 Gy).

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally tolerated radiation dose in men treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. This is a preliminary report of toxicity at Level III (79.2 Gy) on 3D Oncology Group/Radiation Therapy Oncology Group (RTOG) 9406. METHODS AND MATERIALS: Between November 26, 1996 and October 1, 1998, 173 patients with clinically organ-confined prostate cancer (T1 and T2) were accrued to a Level III dose of 79.2 Gy. One hundred sixty-nine patients were available for analysis of toxicity. Patients were registered to two groups according to the risk of seminal vesicle invasion (SVI) on the basis of presenting PSA and Gleason score. Group 1 patients had a calculated risk of SVI <15%, and Group 2 patients had a risk of SVI > or = 15%. For Group 1 patients, the planning target volume (PTV) margins were 5-10 mm around the prostate only. For Group 2 patients, the same margins were applied to the prostate and seminal vesicles (PTV(1)) for the initial 55.8 Gy; then treatment volume was reduced to the prostate only (PTV(2)). To reduce the rectal dose on dose Level III, the minimum PTV dose was limited to 73.8 Gy, whereas the minimum gross target volume dose was 79.2 Gy, both in 44 fractions. The incidence of > or = 3 Grade late effects was compared to that in a similar group of patients treated on RTOG 7506 and 7706 studies. RESULTS: Acute tolerance to 79.2 Gy was excellent with no patients experiencing > or = Grade 3 acute toxicity. The acute toxicity rate was comparable to that reported for previous lower dose levels. With the median follow-up of 3.3 years (range: 0.4-4.4 years), a total of 4 patients (2.4%) experienced Grade 3 late toxicity, three cases of which were related to the bladder, and one related to the rectum. There were no Grade 4 or 5 late complications noted during the period of observation. These results are also comparable to those reported at dose Levels I and II. The expected incidence of > or = 3 Grade 3 late toxicity was calculated using historical data from two previous RTOG prostate cancer trials, 7506 and 7706. The calculated risk accounted for the difference in follow-up duration between patients in this study and the historical experience. The observed rate of > or = Grade 3 late effects for Group 1 (two cases) is significantly lower (p = 0.0002) than the 17.6 cases that would have been expected from the historical control. The observed rate for Group 2 (two cases) was also significantly lower (p = 0.0037) than the 12.1 cases expected. CONCLUSION: Based on excellent tolerance of 3D-CRT for stages T1 and T2 prostate cancer, further biological dose escalation has been pursued to Levels IV and V, 74 Gy and 78 Gy, respectively, at 2 Gy per day, in an attempt to reduce the total treatment duration. This trial has closed. A Phase III comparative RTOG trial is being developed to determine whether high-dose 3D-CRT improves efficacy.

Adult↗

PubMed2002

The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart for intact breast radiation.

PURPOSE: To investigate the impact of radiographic parameter and radiation technique on the volumetric dose of lung and heart for intact breast radiation. METHODS AND MATERIALS: Forty patients with both two-dimensional (2D) and computed tomographic (CT) simulations were enrolled in the study. Central lung distance (CLD), maximal heart distance (MHD), and maximal heart length (MHL) were measured under virtual simulation. Four plans were compared for each patient. Plan A used a traditional 2D tangential setup. Plan B used clinical target volume (CTV) based three-dimensional (3D) planning. Both plans C and D used a combination of a medial breast field with shallow tangents. Plan D is a further modification of plan C. RESULTS: Under the traditional tangential setup, the mean ipsilateral lung dose and volume at 20, 30, and 40 Gy correlated linearly with CLD (R = 0.85 approximately 0.91). The mean ipsilateral lung dose (Gy) approximated 4 times the CLD value (cm), whereas the percentage volume (%) of ipsilateral lung at 20, 30, and 40 Gy was about 10 times the CLD (cm). The mean heart dose and percentage volume at 20, 30, and 40 Gy correlated with MHD (R = 0.76 approximately 0.80) and MHL (R = 0.65 approximately 0.75). The mean heart dose (Gy) approximated 3 times the MHD value (cm), and the percentage volume (%) of the heart at 10, 20, 30, and 40 Gy was about 6 times MHD (cm). Radiation technique impacted lung and heart dose. The 3D tangential plan (plan B) failed to reduce the volumetric dose of lung and heart from that of the 2D plan (plan A). The medial breast techniques (plans C and D) significantly decreased the volume of lung and heart receiving high doses (30 and 40 Gy). Plan D further decreased the 20 Gy volumes. By use of the medial breast technique, the lung and heart dose were not impacted by original CLD and MHD/MHL. Therefore, the improvement from the tangential technique was more remarkable for patients with CLD >or= 3.0 cm (p < 0.001). CONCLUSIONS: The CLD and MHD impact the volumetric dose of lung and heart. The application of 3D planning for tangential breast irradiation does not decrease heart and lung dose. Adding a medial breast port significantly decreases percentage volume (PV) of lung and heart receiving high doses, especially when the CLD is excessive.

Breast Neoplasms↗

PubMed2002

An Internet-ready database for prospective randomized clinical trials of high-dose-rate brachytherapy for adenocarcinoma of the prostate.

PURPOSE: To demonstrate a new interactive Internet-ready database for prospective clinical trials in high-dose-rate (HDR) brachytherapy for prostate cancer. METHODS AND MATERIALS: An Internet-ready database was created that allows common data acquisition and statistical analysis. Patient anonymity and confidentiality are preserved. These data forms include all common elements found from a survey of the databases. The forms allow the user to view patient data in a view-only or edit mode. Eight linked forms document patient data before and after receiving HDR therapy. The pretreatment forms are divided into four categories: staging, comorbid diseases, external beam radiotherapy data, and signs and symptoms. The posttreatment forms separate data by HDR implant information, HDR medications, posttreatment signs and symptoms, and follow-up data. The forms were tested for clinical usefulness. CONCLUSION: This Internet-based database enables the user to record and later analyze all relevant medical data and may become a reliable instrument for the follow-up of patients and evaluation of treatment results.

Adenocarcinoma↗

PubMed2002

Gross tumor volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma.

PURPOSE: Three-dimensional conformal radiation therapy (3D-CRT) has recently become widely available with applications for patients with non-small-cell lung cancer (NSCLC). These techniques represent a significant advance in the delivery of radiotherapy, including improved ability to delineate target contours, choose beam angles, and determine dose distributions more accurately than were previously available. The purpose of this study is to identify prognostic factors in a population of NSCLC patients treated with definitive 3D-CRT. METHODS AND MATERIALS: Between March 1991 and December 1998, 207 patients with inoperable NSCLC were treated with definitive 3D-CRT. Tumor targets were contoured in multiple sections from a treatment planning computed tomography (CT) scan. Three-dimensional treatment volumes and normal structures were reconstructed. Doses to the International Commission on Radiation Units and Measurements (ICRU) reference point ranged from 60 to 83.85 Gy with a median dose of 70 Gy. The median dose inhomogeneity was +/- 5% across planning target volume. Outcome was analyzed by prognostic factors for NSCLC including pretreatment patient and tumor-related factors (age, gender, race, histology, clinical stage, tumor [T] stage, and node [N] stage), parameters from our 3D-CRT system (gross tumor volume [GTV] in cm3), irradiation dose prescribed to isocenter, volume of normal lung exceeding 20 Gy (V20), and treatment with or without chemotherapy. The median follow-up time was 24 months (range, 7.5 months to 7.5 years). RESULTS: One and two-year overall survival rates for the entire group were 59% and 41%, respectively. Overall survival, cause-specific survival, and local tumor control were most highly correlated with the GTV in cm3. On multivariate analysis the independent variable most predictive of survival was the GTV. Traditional staging such as T, N, and overall clinical staging were not independent prognostic factors. Patients receiving ICRU reference doses > or =70 Gy had better local control and cause-specific survivals than those treated with lower doses (p = 0.05). Increased irradiation dose did not improve overall survival. CONCLUSIONS: GTV as determined by CT and 3D-CRT planning is highly prognostic for overall and cause-specific survival and local tumor control and may be important in stratification of patients in prospective therapy trials. T, N, and overall stage were not independent prognostic factors in this population of patients treated nonsurgically. The value of dose escalation beyond 70 Gy should be tested prospectively by clinical trial.

Adult↗

PubMed2002

Trade-off to low-grade toxicity with conformal radiation therapy for prostate cancer on Radiation Therapy Oncology Group 9406.

The aim of this study was to evaluate and compare the rates of grade 2 or worse late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. The authors previously have reported the results of patients treated on the first 2 dose levels of this study with respect to grade 3 or greater late toxicity. This analysis examines the incidence of grade 2 toxicity in this study. From August 1994 to September 1999, 424 patients were entered on this dose escalation trial of 3-dimensional conformal radiation therapy (3D CRT) for localized adenocarcinoma of the prostate at doses of 68.4 Gy (level I) and 73.8 Gy (level II). All radiation prescriptions were a minimum dose to a planning target volume. Patients were stratified according to clinical stage and risk of seminal vesicle invasion based on Gleason score and presenting prostate-specific antigen. Average time at risk after completion of therapy ranged from 33.1 to 40.1 months for patients treated at dose level I and 15.6 to 34.2 months for patients at dose level II. The frequency of late effects > or = grade 2 was compared with a similar group of patients treated on RTOG studies 7506 and 7706 with adjustments made for the interval from completion of therapy. The RTOG toxicity scoring scales for late effects were used. The rate of grade 3 or greater late toxicity continues to be low compared with RTOG historical controls. No grade 4 or 5 late complications were reported in any of the 406 evaluable patients during the period of observation. Interestingly, the incidence of grade 2 late toxicity was increased relative to historical controls in all groups and dose levels. In group 1, level I and group 3, level II, the increase in grade 2 complications was statistically significant; 16 complications were observed in group 1, level I when 9.2 were expected (P =.026) and 22 were observed in group 3, level II when 7.6 were expected (P <.0001). When examining all late effects > or = grade 2, there were no significant differences in the rate of late effects in both groups and both dose levels with the exception of group 1, level II. This, in combination with the statistically significant decrease in late effects > or = grade 3, suggests that in most circumstances there has been a shift of grade 3 complications to grade 2. In group 1, dose level II there was a statistically significant reduction in > or = grade 2 late effects, suggesting there was no shift from grade 3 to grade 2 in these patients. In this circumstance there may have been a global reduction in all complications or a shift to late effects less severe than grade 2. In group 2, dose level II there is a trend (P =.085) toward this same result. It is important to continue to examine late effects closely in patients treated on RTOG 9406. The primary objective of dose escalation without an increase rate of > or = grade 3 complications has been achieved. However, the reduction in grade 3 complications may have resulted in a higher incidence of grade 2 late effects. Because grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Improved conformal treatment delivery with intensity-modulated radiation therapy or the use of radioprotective agents could be considered. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.

Adenocarcinoma↗

PubMed2002

Three-dimensional conformal therapy versus standard radiation therapy in localized carcinoma of prostate: an update.

This study updates technical principles and results of 3-dimensional conformal radiation therapy (3D-CRT) in localized carcinoma of the prostate. Between January 1992 and December 1999, 312 patients were treated with 3D-CRT and 135 patients were treated with bilateral arcs standard radiation therapy (SRT) alone for clinical stage T1b-c or T2 histologically confirmed prostate cancer. None of these patients received hormonal therapy. Mean follow-up for patients in the 3D-CRT group was 3.2 years (range, 2-5.9 years) and for SRT patients, 4.7 years (range, 4-7 years). For 3D-CRT, 7 intersecting fields were used (cerrobend blocking or multileaf collimation) to deliver 68-74 Gy to the prostate. Standard radiation therapy consisted of bilateral 120 degree rotational arcs, with portals using 2-cm margins around the prostate to deliver 68-70 Gy to the prostate. The criterion for chemical disease-free survival was a postirradiation prostate-specific antigen (PSA) value following the American Society for Therapeutic Radiology and Oncology guidelines. Symptoms during treatment were quantitated weekly, and late effects were assessed every 4-6 months. Dose-volume histograms showed a two-thirds reduction with 3D-CRT in normal bladder or rectum receiving > or = 70 Gy with 3D-CRT. Higher 5-year chemical disease-free survival was observed with 3D-CRT (75%; for T1b-c and 79%; for T2 tumors) compared with SRT (61% and 65%, P = 0.01 and P = 0.12, respectively). There was no statistically significant difference in chemical disease-free survival in patients with Gleason score of < or = 4 (P = 0.85), but, with Gleason score of 5-7, the 5-year survival rates were 83% with 3D-CRT and 59% with SRT (P < or = 0.01). In 245 patients with pretreatment PSA of < or = 10 ng/mL treated with 3D-CRT, the chemical disease-free rate was 80% versus 72% in 98 patients treated with SRT (P = 0.21). In patients with PSA of 10.1-20 ng/mL, the chemical disease-free survival rate for 50 patients treated with 3D-CRT was 71% compared with 43% for 20 patients treated with SRT (P = 0.02). The corresponding values were 59% and 16%, respectively, for patients with PSA levels > 20 ng/mL (P = 0.09). On multivariate analysis, the most important prognostic factors for chemical failure were pretreatment PSA (P = 0.004), nadir PSA (P = 0.001), and 3D-CRT technique (P = 0.012). Moderate dysuria was reported by 2%-5% of patients treated with 3D-CRT in contrast to 6%-9% of patients treated with SRT. The incidence of moderate loose stools or diarrhea, usually after the fourth week of treatment, was 3%-5% in the 3D-CRT patients and 8%-19% in the SRT group. Late intestinal grade 2 morbidity (proctitis or rectal bleeding) was 1% in the 3D-CRT group in contrast to 7% in SRT patients. The 3D-CRT spares more normal tissues, yields higher chemical disease-free survival, and results in less treatment morbidity than SRT in treatment of stage T1-T2 prostate cancer. Follow-up at > or = 10 years is needed to confirm these observations.

Adenocarcinoma↗

PubMedDate not supplied

Serum total gangliosides and TA90-IC levels: novel immunologic markers in colorectal cancer.

BACKGROUND: Because of the challenge in defining prognostic markers predictive of recurrence or progression, carcinoembryonic antigen (CEA) remains the most frequently used marker in colorectal cancer, despite its low sensitivity. We hypothesized that TA90-IC status and serum ganglioside levels might be useful markers and might be of prognostic significance in colorectal cancer. METHODS: Serum samples from 68 patients undergoing surgical treatment for histologically proven colorectal cancer were analyzed for the presence of CEA, serum gangliosides, and TA90-IC. Forty-one patients had node-negative disease, whereas 27 patients had limited metastatic disease. The intent was curative resection, even for patients with metastatic disease. Cryopreserved serum specimens were analyzed in a blinded fashion for total serum ganglioside levels (by an assay that detects lipid-associated sialic acids), for CEA, and for TA90-IC (by a murine monoclonal antibody-based enzyme-linked immunosorbent assay). A positive value for TA90-IC levels was defined as an optical density (OD) of more than 0.410 at 405 nm. RESULTS: Serum ganglioside levels were elevated more frequently than CEA concentrations (84% vs 44%). The combination of serum ganglioside and CEA values was more sensitive (88%) than CEA value alone (44%) in identifying patients with early-stage colorectal cancer. TA90-IC levels were elevated more frequently than CEA concentrations (56% vs 32%). The combination of TA90-IC and CEA values was more sensitive (72%) than CEA value alone (32%) in identifying patients with advanced-stage colorectal cancer. At an enzyme-linked immunosorbent assay cutoff level of 0.410, 15 (56%) patients had positive TA90-IC values. Fourteen patients alive with residual disease had a median OD TA90-IC level of 0.879, and only three patients had levels below the OD cutoff value of 0.410. Thirteen patients with no evidence of disease had a median level of 0.277, and only four patients had OD levels > or = 0.410. TA90-IC was significantly higher in the alive with residual disease patients than those rendered no evidence of disease (P = 0.02). CONCLUSIONS: We speculate that a multiple-marker analysis that combines CEA values with serum ganglioside and TA90-IC values may be more sensitive than CEA value alone for detecting colorectal cancer. The potential prognostic significance of TA90-IC status in advanced disease warrants further investigation.

Adult↗

PubMedDate not supplied

Serum anti-ganglioside IgM antibodies in soft tissue sarcoma: clinical prognostic implications.

PURPOSE: Gangliosides are tumor-associated antigens with many biologic functions, including complex interactions with cytokines and other modulators of the immune system. Serum total ganglioside level may be an ideal surrogate marker to predict tumor burden and response to treatment. Antibodies produced against tumor gangliosides may help predict survival. The purpose of this study is to determine whether the serum total ganglioside levels might predict the tumor burden in patients with soft tissue sarcoma, and whether the augmented anti-ganglioside immunoglobulin M (IgM) response might reflect the clinical outcome of these patients. METHODS: Serum TG levels were measured in the cryopreserved sera by estimating lipid-associated sialic acids from 97 patients before surgical resection of soft tissue sarcoma and from 39 age- and gender-matched healthy volunteers. All sera were analyzed for IgM titers (expressed natural log) by enzyme-linked immunosorbent assay against eight gangliosides (GM1, GM2, GM3, GD3, GD2, GD1a, GD1b, and GT1b). Cox regression was used for univariate and multivariate analyses of the variables affecting progression-free and overall survival. RESULTS: Serum TG levels were higher in soft tissue sarcoma patients than in healthy individuals (21.8 + 7.7 vs 16.1 + 2.7 mg/dL; P = 0.001). Larger tumors, high histologic grade, and more advanced stage of disease correlated with higher serum total ganglioside levels (P < 0.05). Anti-ganglioside titers to GM3, GD2, and GT1b were significantly higher in patients with soft tissue sarcoma, whereas anti-GD1a and GD1b titers were significantly higher in healthy subjects. The titers of antibodies against GM1, GM2, and GD3 in patients with soft tissue sarcoma were comparable to those of the healthy individuals. When compared with healthy controls, patients with low-grade tumors had higher titers of anti-GT1b, anti-GM3, and anti-GD2 antibodies, and patients with high-grade tumors had higher titers of anti-GT1b and anti-GD2 antibodies. These data suggest that the predominant gangliosides expressed by sarcomas may include GT1b and GD2. In addition, low-grade tumors may express an immunogenic species of GM3. On both univariate and multivariate analyses, augmented anti-GD1a IgM titers, age > 50 years, and retroperitoneal location were predictive of decreased overall survival, whereas augmented anti-GT1b titers were predictive of improved overall survival. CONCLUSIONS: Serum TG level may be a useful marker of tumor burden and response to treatment for soft tissue sarcoma. Anti-GD1a and anti-GT1b IgM titers predicted survival and may be of therapeutic and prognostic value in the management of soft tissue sarcoma.

Adolescent↗

PubMedDate not supplied

Conservation therapy in T1-T2 breast cancer: past, current issues, and future challenges and opportunities.

PURPOSE: To assess the significance of patient age, race, tumor-related prognostic parameters, status of surgical excision margins, and irradiation boost on incidence of ipsilateral breast relapse, and to review current issues in the management of T1-T2 breast cancer patients with conservation therapy. MATERIALS AND METHODS: Records of 1037 patients with histologically confirmed stage T1 and 308 patients with T2 carcinoma of the breast treated with breast conservation therapy from January 1970 through December 1997 were prospectively registered and evaluated. The mean follow-up for surviving patients was 6.6 years (range, 4-30 years), with a minimum follow up of 4 years for all patients. RESULTS: There were 78 ipsilateral breast relapses (IBRs); the actuarial 10-year incidence of IBR was 7% for T1 and 11% for T2 tumors. In patients 40 years of age or younger, four of 24 (17%) with extensive intraductal component developed an ipsilateral breast relapse, compared with six of 80 (8%) without extensive intraductal component, in contrast to eight of 159 (5%) and 33 of 776 (4%) in postmenopausal patients with or without extensive intraductal component, respectively. In patients with T2 tumors, two of eight (25%) women 40 years or younger with extensive intraductal component, and seven of 50 (14%) without extensive intraductal component developed ipsilateral breast relapse. The corresponding values for the patients older than 40 years were five of 48 (10%) and 13 of 202 (6%), respectively. The incidences of ipsilateral breast relapses, correlated with status of surgical margins after re-excision in T1 tumors, were one of 30 (3.3%) for positive, no relapses in 40 patients with close margins, 16 of 438 (3.6%) for negative, and 18 of 196 (9%) for undetermined margins. In the patients with T2 tumors, ipsilateral breast relapses occurred in two of 16 patients (12.5%) with positive margins, one of 16 (6%) with close, seven of 105 (6.6%)with negative, and four of 68 (5.9%) with undetermined margins (differences not statistically significant). In patients with T1 tumors, negative margins, the 10-year relapse rate was the same (8%) in 559 to whom a boost was administered and in 66 without a boost. In patients with positive margins, the relapse rate was 4% in 215 receiving a boost (18-20 Gy) and 33% (two of six) without a boost. In patients with T2 tumors and negative margins, the rate of ipsilateral breast relapses in 16 patients to whom no boost was given was 12%, as opposed to 10% in 143 patients who received a boost. However, with T2 tumors and close or positive margins, the IBR rate at 10 years was 12% in 81 given a boost, in contrast to 40% (2 of 5) without a boost. In T1 tumors, the breast failure rate was two of 53 (3.7%) in women < or = 40 years receiving chemotherapy and eight of 51 (15.6%) without chemotherapy. For T2 tumors, the corresponding values were seven of 39 (17%) and two of 19 (10.5%), respectively. In women 40 years or younger with T1 tumors receiving hormones or not, the ipsilateral breast relapse rate was two of 19 (10.5%) and eight of 85 (9.4%), respectively; in the older than 40 years group, the corresponding values were six of 377 (1.6%) and 35 of 558 (6.2%). In the patients with T2 tumors, ipsilateral breast relapse rates were not statistically different in the various groups. On multivariate analysis, only age and adjuvant therapy were significant factors predictive of ipsilateral breast relapse. CONCLUSIONS: Surgical excision margins status following adequate doses of radiation therapy was not a predictor of ipsilateral breast relapse. In patients younger than 40 years of age with extensive intraductal component, a somewhat higher breast relapse rate was noted but not enough to preclude breast conservation therapy. A boost of irradiation did not have a significant impact in the incidence of ipsilateral breast relapse in patients with negative margins, but it was of benefit to those with close or positive margins. Close attention to surgical margin status and delivery of higher doses of irradiation to the tumor excision site in patients with close or positive surgical margins will decrease the probability of breast relapses.

Adult↗