Seed implant retention score predicts the risk of prolonged urinary retention after prostate brachytherapy.

PURPOSE: To risk-stratify patients for urinary retention after prostate brachytherapy according to a novel seed implant retention score (SIRS). PATIENTS AND METHODS: A total of 835 patients underwent transperineal prostate seed implant from March 1993 to January 2007; 197 patients had (125)I and 638 patients had (103)Pd brachytherapy. Four hundred ninety-four patients had supplemental external-beam radiation. The final downsized prostate volume was used for the 424 patients who had neoadjuvant hormone therapy. Retention was defined as reinsertion of a Foley catheter after the implant. RESULTS: Retention developed in 7.4% of patients, with an average duration of 6.7 weeks. On univariate analysis, implant without supplemental external-beam radiation (10% vs. 5.6%; p = 0.02), neoadjuvant hormone therapy (9.4% vs. 5.4%; p = 0.02), baseline alpha-blocker use (12.5% vs. 6.3%; p = 0.008), and increased prostate volume (13.4% vs. 6.9% vs. 2.9%, >45 cm(3), 25-45 cm(3), <25 cm(3); p = 0.0008) were significantly correlated with increased rates of retention. On multivariate analysis, implant without supplemental external-beam radiation, neoadjuvant hormone therapy, baseline alpha-blocker use, and increased prostate volume were correlated with retention. A novel SIRS was modeled as the combined score of these factors, ranging from 0 to 5. There was a significant correlation between the SIRS and retention (p < 0.0001). The rates of retention were 0, 4%, 5.6%, 9%, 20.9%, and 36.4% for SIRS of 0 to 5, respectively. CONCLUSIONS: The SIRS may identify patients who are at high risk for prolonged retention after prostate brachytherapy. A prospective validation study of the SIRS is planned.

Salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy.

PURPOSE: To determine the toxicity and clinical outcome of salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy. METHODS AND MATERIALS: Twenty-one patients underwent (103)Pd salvage brachytherapy (median minimum peripheral dose, 90Gy) after local failure after external beam radiation (median dose, 66.6Gy) from 1/21/1998 to 4/5/2005. The median age was 72 years. Six patients had prior transurethral resection of the prostate. The median Gleason score was 7 and the median preimplant prostate-specific antigen was 3.8. Twelve patients received concurrent androgen ablation with prostate brachytherapy. Biochemical failure was defined as three consecutive rises in prostate-specific antigen scored at the call date, initiation of hormone therapy, or clinical failure. Toxicity was defined according to the National Cancer Institute common toxicity criteria and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. RESULTS: With a median followup of 36 months, the actuarial 3-year and 5-year overall survival rates were 81% and 81%, and the biochemical failure-free survival rates were 94% and 38%, respectively. There was no significant difference in biochemical failure-free survival (p=0.98) and overall survival (p=0.13) for patients who had androgen ablation. Four patients developed biochemical failure and 1 patient developed distant metastasis at 59 months from treatment. Four patients had Grade 2 genitourinary adverse events, 2 patients had Grade 1 genitourinary adverse events, and 1 patient had a Grade 2 gastrointestinal adverse event. There were no Grade 3 or higher adverse events. All three deaths were secondary to other medical comorbidities. CONCLUSIONS: Salvage prostate brachytherapy after external beam radiation failure can be safely performed with acceptable biochemical control. This treatment option should be considered for patients who have prolonged life expectancy after localized external beam radiation failure.

2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma.

BACKGROUND: The current study was performed to assess the value of 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting the pathologic response and survival of patients with esophageal carcinoma treated with preoperative chemoradiation (CRT) and tumor resection. Preliminary reports suggest that FDG-PET may be predictive of the response of esophageal carcinoma patients to preoperative CRT. METHODS: Eighty-three patients with resectable esophageal carcinoma who underwent preoperative CRT and FDG-PET and tumor resection were evaluated for pathologic response to CRT, percent residual tumor, and survival. RESULTS: The majority of patients in the current study were men (74 of 83 patients; 89%). Most tumors were adenocarcinomas (73 of 83 tumors; 88%) and clinical (EUS)T3/4 (69 tumors; 83%) or N1 (46 tumors; 55%). FDG-PET after preoperative CRT identified pathologic responders but failed to rule out microscopic residual tumor in 13 of 73 cases (18%). Pathologic response was found to correlate with the post-CRT FDG-PET standardized uptake value (SUV) (P = 0.03) and a post-CRT FDG-PET SUV of or 4 was found to be the only preoperative factor to correlate with decreased survival (2-year survival rate of 33% vs. 60%; P = 0.01). On univariate Cox regression analysis, only post-CRT FDG-PET was found to be correlated with post-CRT survival (P = 0.04). CONCLUSIONS: Post-CRT FDG-PET was found to be predictive of pathologic response and survival in patients with esophageal carcinoma who undergo preoperative CRT. Esophagectomy should still be considered even if the post-CRT FDG-PET scan is normal because microscopic residual disease cannot be ruled out.

Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial.

PURPOSE: To determine the ability of amifostine to reduce the severity and/or incidence of the acute toxicities of concurrent chemotherapy and radiotherapy (RT) for non-small-cell lung cancer. METHODS AND MATERIALS: Patients with inoperable, nonmetastatic non-small-cell lung cancer receiving concurrent chemoradiotherapy were randomized to one of two treatment groups. Arm 1 patients received thoracic RT (total dose, 69.6 Gy in 58 fractions of 1.2 Gy b.i.d. 5 d/wk), plus oral etoposide (50 mg b.i.d. 30 min before thoracic RT for 10 days, repeated on Day 29) and cisplatin (50 mg/m2 i.v. on Days 1, 8, 29, and 36). Arm 2 patients received the same treatment plus amifostine (500 mg i.v. 20-30 min before any treatment the first 2 days of each week). Acute effects were assessed using the National Cancer Institute Common Toxicity Criteria. RESULTS: Sixty-two patients were enrolled between November 1998 and January 2001. The minimal follow-up was 24 months, and the median follow-up of living patients was 31 months. The patient and tumor characteristics were equally distributed between the patients in the two arms. The median survival time was 20 months in Arm 1 patients and 19 months in Arm 2 patients. The maximal esophageal toxicity was mild (Grade 1) in 23%, moderate (Grade 2) in 42%, and severe (Grade 3-4) in 35% of patients in Arm 1; the corresponding rates for the Arm 2 patients were 48%, 35%, and 16% (p = 0.021). Severe pneumonitis occurred in 16% of the Arm 1 and none of the Arm 2 patients (p = 0.020, chi-square test). Neutropenic fever occurred in 39% of Arm 1 and 16% of Arm 2 patients (p = 0.046, chi-square test). Mild hypotension, dysgeusia, and sneezing were significantly more frequent among the patients in Arm 2. CONCLUSION: Amifostine reduced the severity and incidence of acute esophageal, pulmonary, and hematologic toxicity resulting from concurrent cisplatin-based chemotherapy and RT. Amifostine had no apparent effect on survival in these patients with unresectable non-small-cell lung cancer, suggesting that it does not have a tumor-protective effect.

Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters.

PURPOSE: To clarify the relationship between the percentage of lung receiving low radiation doses with concurrent chemotherapy and the occurrence of postoperative pulmonary complications in the treatment of esophageal carcinoma. METHODS: From 117 patients who underwent preoperative chemoradiation for esophageal cancer at our institution between 1998 and 2002, we selected 61 patients for whom complete pulmonary dose-volume histogram (DVH) data were available and analyzed the incidence of pneumonia and acute respiratory distress syndrome (ARDS) in this group. All patients received concurrent chemoradiation therapy, and 39 patients also received induction chemotherapy before concurrent chemoradiation. The median age was 62 years, and the median radiotherapy dose was 45 Gy. The percentage of lung volume receiving at least 10 Gy (V10), 15 Gy (V15), and 20 Gy (V20) were recorded from each pulmonary DVH. RESULTS: Eleven (18%) of the 61 patients had pulmonary complications, 2 of whom died after progression of pneumonia. Pulmonary complications were noted more often (35% vs. 8%, p = 0.014) when the pulmonary V10 was > or =40% vs. <40% and when the V15 was > or /=30% vs. < 30% (33% vs. 10%, p = 0.036). An apparent increase in pulmonary complication rate when V20 was > or =20% vs. <20% (32% vs. 10%, p = 0.079) was not significant. None of the other factors analyzed (surgical procedure, tumor location, use of induction chemotherapy, use of concurrent taxane-based chemoradiation, or smoking history) was associated with the occurrence of pulmonary complications. The median hospital stay was 17 days for patients who had pulmonary complications vs. 12 days for patients who did not (p = 0.08). CONCLUSIONS: The use of multimodality therapy may require minimization of lung volume irradiation to levels lower than previously expected. Radiotherapy techniques that decrease the volume of lung receiving low radiation doses may significantly reduce the risk of this potentially life-threatening complication.

Dosimetric consequences of using a surrogate urethra to estimate urethral dose after brachytherapy for prostate cancer.

PURPOSE: To assess the accuracy and dosimetric consequences of defining a surrogate urethra at the geometric center of the prostate in postimplant CT scans. METHODS AND MATERIALS: Eighty postimplant CT scans were obtained with a Foley catheter in place at Day 0 and at 1 month for 40 patients who had undergone (125)I prostate brachytherapy. The percentage of urethral volume receiving at least 275% of the prescribed dose (uV(275)), uV(250), uV(200), uV(150), maximal dose received by 90% of urethral volume (uD(90)), uD(70), uD(30), and uD(1) were measured for the Foley catheter and surrogate urethra. The distance between the Foley catheter and surrogate urethra was measured at the base, middle, and apex of the prostate. RESULTS: A statistically significant difference was found in all the above-listed dosimetric parameters between the Foley catheter and surrogate urethra at Day 0 (p

The prognostic value of neurologic function in astrocytic spinal cord glioma.

To assess the prognostic value of neurologic function (NF) in patients with astrocytic spinal cord glioma, we conducted a retrospective study of 25 patients who were treated at our institution between January 1970 and December 1999. The median age was 40 years, and the median follow-up was 54 months. Nineteen patients had a biopsy, 5 had a subtotal resection, and 1 had a gross total resection. Twenty-two patients received postoperative radiotherapy to a median dose of 45 Gy. NF ratings of 1 and 2 were considered favorable, and 3 and 4 were considered unfavorable, based on a scale of 1 to 4. Dual neuropathologic review confirmed the tumor to be low, intermediate, or high grade, based on the WHO grades I-II, III, or IV, respectively. Actuarial rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed. Our study results revealed that an improved 5-year OS rate was associated with favorable NF at diagnosis (73% vs. 22% for patients with unfavorable NF; P = 0.04) and favorable NF before radiation therapy (89% vs. 28% for patients with unfavorable NF; P = 0.049). There was a significant difference in OS based on tumor grade ( P < 0.001) and age (risk ratio, 1.04; P = 0.027). PFS and LC were significantly better for young patients and those with lower tumor grade ( P < 0.05). A multivariate analysis of age, NF at diagnosis, and postoperative NF for all patients showed postoperative NF and age to be independent prognostic factors for OS. We conclude that favorable NF may be associated with improved outcome in patients with astrocytic spinal cord glioma.

Is intraoperative nomogram-based overplanning of prostate implants necessary?

PURPOSE: Several investigators have described intraoperative planning of prostate implants based on a nomogram. The aim of this work was to investigate the adequacy of the nomogram in predicting the total activity necessary for optimal dosimetry. METHODS AND MATERIALS: Eighty CT-based postimplant treatment plans were performed for patients who underwent ultrasound guided I-125 permanent implants alone between April 2000 and March 2001. The cohort of 40 patients had early stage (T1-T2) prostatic carcinoma and pre-treatment prostate volumes of 19-50 cc. I-125 seeds (0.391 mCi/seed) were implanted to achieve a distribution of 75% of the activity peripherally and 25% centrally. The CT studies were obtained on the day of (CT1) and at 1 month (CT2) after implant. All patients were catheterized at CT1, and 28 patients were catheterized at CT2 to visualize the urethra. For each patient, the percentage difference (dA) between the total implanted and nomogram predicted activity for a known prostate volume was calculated. The V200 (volume receiving 200% of the prescribed dose), V150, V100, V90, D100 (maximum dose received by 100% of the volume), D90, and D80 were measured for the prostate at CT1 and CT2. For the urethra, V275, V250, V200, and V150 were evaluated, and V100 and V70 were evaluated for the rectum. The Pearson test was used to correlate the dosimetric parameters with dA. Linear regression was used to fit the correlation of the volume and dose parameters with dA. RESULTS: The median V100 at CT1 and CT2 was 91.8% and 94.2%, respectively. The Pearson test was significant for the prostate V100 and dA measured at CT1 (p = 0.005) but not at CT2 (p = 0.106). A similar correlation was found for the prostate D90 at CT1 (p = 0.002), but not at CT2 (p = 0.076). D100 (maximum dose received by 100% of volume) for prostate did not correlate with dA at CT1 (p = 0.094) and CT2 (p = 0.148). The volume of the prostate receiving higher doses (greater than 150% and 200% of the prescribed dose) correlated with dA. There were no significant correlations between V275, V250, V200, and V150 at CT1 and CT2 as a function of dA for the urethra. V100 and V70 for the rectum correlated significantly with dA; for V100, p = 0.041 at CT1 and p = 0.014 at CT2 and for V70, p = 0.041 at CT1 and p = 0.026 at CT2. A linear regression model fitted to the prostate data obtained from CT1 with the goal of achieving a V100 of 90% and D90 of 145 Gy suggests that no increase in the number of seeds may be warranted using intraoperative planning. The implants examined showed no concomitant increase of urethral doses with increase in activity relative to the nomogram, but showed an increase in the rectal doses for the same increase in activity. CONCLUSION: The doses evaluated at CT1 represent an underestimate, whereas those obtained at CT2 represent an overestimate of the actual delivered protracted permanent implant dose. Based on these results and consideration of the dynamic nature of the dose distribution, target coverage obtained with intraoperative planning using the nomogram predicted activity is consistent with published guidelines for a quality implant and critical structure doses are within tolerance.

Target definition and contouring in carcinoma of the lung and esophagus.

The optimal treatment for intrathoracic tumors such as lung and esophageal cancer requires an improvement of therapeutic ratio to increase efficacy of the cancer-cell kill and decrease the normal-cell kill. This is not an easy task because sensitive normal cells such as alveoli and epithelial cells in the esophagus and bronchus surround these tumors. How to minimize the damage of such sensitive normal cells within irradiated fields without sparing cancer cells is a major issue for radiation oncologists, especially as concurrent chemoradiotherapy has become more standard treatment. One way to achieve this task is accurate delineation of the target volume, which will be emphasized here. Some other ways to achieve it are biological protection by ethyol, keratinocyte growth factors, biologically targeted treatments such as C225 and celecoxib, and anti-angiogenesis, which have been briefly addressed in Dr. Cox's article in this Journal. Molecular imaging is a new diagnostic and therapeutic modality that offers great potential for accuracy of target definition, although it is not quite ready for routine clinical use at the present time. Accurate target definition and contouring in cases of carcinoma of the lung and esophagus depend on expertise of diagnostic and therapeutic medical teams. There we review the normal anatomy, diagnostic methods, and tumor delineation of cancer of the lung and esophagus.

Uncertainties in contemporary treatment of aggressive lymphomas.

Contemporary treatment of malignant lymphomas relies on systemic chemotherapy. The role of radiation therapy is often debated. Randomized clinical trials have shown that the addition of radiation therapy, following complete response (CR) to several cycles of combination chemotherapy for early stage diffuse large B-cell and immunoblastic lymphoma, increases disease-free survival. The dose required to achieve consistent control after complete response is uncertain, but the available data suggest a dose-response for tumor control after CR. The role of radiation therapy after partial response (PR) is uncertain as many such patients are advised to undergo high dose chemotherapy followed by bone marrow reconstitution. Involved field radiation therapy after PR is able to achieve durable freedom-from-relapse. The role of radiation therapy for peripheral T-cell lymphomas and mediastinal T-cell lymphoblastic lymphomas is also uncertain. Finally, in the era of combination chemotherapy and conformal irradiation, a uniform understanding of what constitutes "involved field" treatment volume is lacking. This issue is even more complex now that intensity-modulated irradiation has become widely available. It is unlikely that these questions will be addressed in randomized clinical trials.

Outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas.

There is little information in the literature on outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas. The purpose of this study was to analyze The University of Texas M.D. Anderson Cancer Center results in such patients. From 1985 to 1998, 39 patients with Stage I or II World Health Organization classification anaplastic large cell lymphoma (ALCL; n = 20), peripheral T-cell lymphoma, unspecified (PTCLu; n = 11), or nasal-type NK/T-cell lymphoma (NKTCL; n = 8) were treated using doxorubicin-based chemotherapy (median, 6 cycles) with (n = 24) or without (n = 15) radiotherapy (median dose, 40 Gy). Median age was 41 years. Median follow-up of surviving patients was 85 months. Even though patients who presented with bulky disease or who achieved less than a complete response to chemotherapy were the ones typically treated with combined modality therapy rather than chemotherapy alone, there was no significant difference in local control (5-year rates: 60 vs. 70%, p = 0.49), progression-free survival (5-year rates: 65 vs. 60%, p = 0.62), or overall survival (5-year rates: 74 vs. 67%, p = 0.47) between the groups treated with combined modality therapy and chemotherapy alone. Fifteen (38%) patients relapsed. Twelve relapses were limited to the initial site of disease; two involved the initial site and new sites, and one involved only new sites. Based on the significant risk of relapse at the initial site of disease, different approaches, including chemotherapy with concomitant radiotherapy to doses > or = 45 Gy, warrant investigation.