Comparison of Three Groups of Patients Having Low Dose Rate Prostate Brachytherapy: Prostate-Specific Antigen Failure and Overall Survival.

Purpose To examine dosimetric and clinical outcomes for Cs-131 radioactive seed implant compared to Pd-103 and I-125.  Background/Significance Cs-131 is a novel isotope with relatively short half-life (9.7 days) that may have clinical advantages in seed implant treatments of prostate cancers. There may be a shorter duration of symptoms and increased PSA control rates. Methods We performed a retrospective study in which clinical and dosimetric outcomes were compared for 186 prostate implants performed over a ten-year time period at three different Ascension hospitals. Isotopes that were used included Cs-131 (n=66; half-life 9.7 days), I-125 (n=60; half-life 60 days), and Pd-103 (n=60; half-life 17 days) Results The implants used standard radiation dosages. These were 145 Gy for I-125 alone or 109 Gy when combined with external beam radiation. In the case of Cs-131 used alone, the dose was 115 Gy or 85 Gy when combined with an external beam. For Pd-103, 125 Gy was used for monotherapy and 90 Gy when combined with an external beam. The Cs-131 dosimetry was found to be similar to I-125 and Pd-103 on a quantitative basis. However, there was better homogeneity, and the delivered activity per seed and the number of seeds employed were greater compared to other isotopes. We compared the corrected total source strengths (i.e. normalized to sample mean values) and were able to demonstrate similar distributions for the three isotopes. Dosimetric analysis also suggested there was superior homogeneity with Cs-131. The median PSA value at 60 months was 0.11 ng/ml. There were only a few PSA failures in the three groups of cases, nonetheless, the Cs-131 had the fewest.  Conclusions One attractive option for men with early-stage prostate cancer is interstitial brachytherapy. The use of the shorter-acting Cs-131 isotope may be expected to have dose-related side effects that resolve more rapidly. This series suggests a trend for improved PSA control outcomes for Cs-131 patients compared with I-125 and Pd-103.

Rare tumors: Retinoblastoma, nasopharyngeal cancer, and adrenocorticoid tumors.

The role of surgery, chemotherapy, and radiation therapy for retinoblastoma has evolved considerably over the years with the efficacy of intraarterial chemotherapy and the high incidence of secondary malignant neoplasms following radiation therapy. The use of spot scanning intensity-modulated proton therapy may reduce the risk of secondary malignancies. For pediatric nasopharyngeal carcinoma, the current standard of care is induction chemotherapy followed by chemoradiation therapy. For adrenocortical carcinoma, the mainstay of treatment is surgery and chemotherapy. The role of radiation therapy remains to be defined.

Radiation and depression associated with complications of tissue expander reconstruction.

PURPOSE: Rates of implant failure, wound healing delay, and infection are higher in patients having radiation therapy (RT) after tissue expander (TE) and permanent implant reconstruction. We investigated pretreatment risk factors for TE implant complications. PATIENTS AND METHODS: 127 breast cancer patients had TE reconstruction and radiation. For 85 cases of bilateral TE reconstruction, the non-irradiated breast provided an internal control. Comparison of differences in means for continuous variables used analysis of variance, then multiple pairwise comparisons with Bonferroni correction of p value. RESULTS: Mean age was 53 ± 10.1 years with 14.6% African-American. Twelve (9.4%) were BRCA positive (9 BRCA1, 4 BRCA2, 1 Both). Complications were: Grade 0 (no complication; 43.9%), Grade 1 (tightness and/or drifting of implant or Baker Grade II capsular contracture; 30.9%), Grade 2 (infection, hypertrophic scarring, or incisional necrosis; 9.8%), Grade 3 (Baker Grade III capsular contracture, wound dehiscence, or impending exposure of implant; 5.7%), Grade 4 (implant failure, exchange of implant, or Baker Grade IV capsular contracture; 9.8%). 15.3% (19 cases) experienced Grade 3 or 4 complication and 9.8% (12 cases) had Grade 4 complication. Considering non-irradiated breasts, there were two (1.6%) Grade 3-4 complications. For BMI, there was no significant difference by category as defined by the CDC (p = 0.91). Patients with depression were more likely to experience Grade 3 or 4 complication (29.4 vs 13.2%; p = 0.01). Using multiple logistic regression to predict the probability of a Grade 3 or 4 complications in patients with depression were found to be 4.2 times more likely to have a Grade 3 or 4 complication (OR = 4.2, p = 0.03). CONCLUSIONS: Higher rates of TE reconstruction complications are expected in patients receiving radiotherapy. An unexpected finding was that patients reporting medical history of depression showed statistically significant increase in complication rates.

Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.

PURPOSE: This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. PATIENTS AND METHODS: Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. RESULTS: The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. CONCLUSION: Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. This regimen should be included as a backbone for further studies.

A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893.

BACKGROUND: The aims of this study were to determine the feasibility of the combination of low dose, anti-angiogenic chemotherapy with standard therapy for patients with metastatic Ewing sarcoma (ES), and to obtain preliminary outcome data. PROCEDURES: Patients with metastatic ES were eligible. Therapy consisted of alternating cycles of ifosfamide-etoposide, and vincristine, doxorubicin, cyclophosphamide. Vinblastine and celecoxib were concomitantly administered. Surgical, radiotherapeutic, or combination local control therapy was given per institutional preference. RESULTS: Thirty-five eligible patients were enrolled. Ninety percent received at least 75% of planned vinblastine/celecoxib doses. There was no excess of neurologic, infectious, hemorrhagic, or cardiovascular toxicities. However, 7 of 21 patients who received pulmonary irradiation prior to experiencing pulmonary toxicity did develop grade 2 or greater pulmonary toxicity, including two deaths of apparent radiation pneumonitis. Fourteen of 16 patients with pelvic disease received local irradiation. Hemorrhagic cystitis developed in six patients, five of whom had received pelvic irradiation. The overall 24-month event free survival was 35% (19-51%); 71% (26-92%) for the seven with isolated pulmonary metastases, 26% (10-45%) for all others. CONCLUSION: The combination of vinblastine/celecoxib metronomic therapy with standard ES treatment was feasible according to the protocol definitions. However, excess toxicity in irradiated areas was noted and limits the usefulness of this protocol. The 24-month EFS for those with isolated pulmonary metastases is better than historical controls, although the number of patient number is small, follow up short and we are lacking contemporaneous controls.

Three-dimensional visualization and dosimetry of stranded source migration following prostate seed implant.

PURPOSE: Computed tomographic (CT) imaging was used to determine the displacement of stranded seeds between day 0 and day 30 following prostate seed implants. Post-plan dosimetry was used to assess the dosimetric consequence of strand displacement. METHODS AND MATERIALS: Between March 2006 and December 2009, 86 prostate seed implant patients had day 0 and day 30 post-plan CT imaging. Migrated strands were first identified by inspection of day 0 and day 30 scans. The exact distance of displacement was measured using 3-dimensional fusion software. Post-plan dosimetric analysis was performed using CMS software. RESULTS: Of the 1550 strands placed, 23 strands exhibited substantial movement and these displacements occurred in 21 of the 86 cases. The measured distance of strand movement ranged from 0.31 cm to 3.44 cm, with mean displacement of 2.75 cm. Of the displaced strands, 15 strands moved away from the implant center while 8 strands moved toward the implant center. A comparison of changes in dosimetric parameters between day 0 and day 30 revealed expected increases in D90 related to resolution of prostate edema. When cases of strand displacement were compared with cases without displacement, there were no differences in D90 or V100 at day 0. At day 30, however, statistically significant decreases in D90 (96.8% vs 89.5%; P = .0061) and V100 (85.9% vs 82.2%; P = .046) were noted for cases with strand displacement. When the data were analyzed by looking at the change in dosimetric parameters over time for each individual case (eg, comparing the difference in D90 from day 0 to day 30 per patient) there was a trend toward decrease in D90 with displacement of the strands but this did not achieve statistical significance (P = .09). CONCLUSIONS: Stranded seeds show unexpected spatial instability in the craniocaudal dimension. Strand displacement may occur in approximately 1.5% of stranded sources placed and about 25% of cases. One may expect mean decreases in D90 and V100 of about 7% and 3%, respectively, among cases exhibiting strand migration in the first month following seed implant. Resolution of prostate edema during the same time period accounts for an approximately 30% increase in D90 and V100.

Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ: analysis of surveillance, epidemiology, and end results data.

PURPOSE: Noninvasive lesions involving the lobules of the breast are increasingly diagnosed as incidental microscopic findings at the time of lumpectomy or core-needle biopsy. We investigated the incidence rates of invasive breast cancer (IBC) after a diagnosis of lobular carcinoma-in-situ (LCIS) by using Surveillance, Epidemiology, and End Results (SEER) data. PATIENTS AND METHODS: Patients (N = 4,853) having a diagnosis of primary LCIS in the time period of 1973 to 1998 were identified using the SEER Public Use CD-ROM data. The database was then searched for patients with subsequent primary IBC occurrences (n = 350). The clinical and pathologic characteristics of patients with subsequent primary IBCs were compared with the characteristics of patients with primary IBCs attained during the same time period (N = 255,114). RESULTS: The incidence of IBC increased over time from diagnosis of LCIS, with 7.1% +/- 0.5% incidence of IBC at 10 years. IBCs detected after partial mastectomy occurred in either breast (46% ipsilateral and 54% contralateral); however, after mastectomy, most IBCs were contralateral (94.7%). IBCs occurring after LCIS more often represented invasive lobular histology (23.1%) compared with primary IBCs (6.5%). The standardized incidence ratio (the ratio of observed to expected cases) for developing IBC was 2.4 (95% CI, 2.1 to 2.6) adjusted for age and year of diagnosis. CONCLUSION: LCIS is associated with increased risk of subsequent invasive disease, with equal predisposition in either breast. The minimum risk of developing IBC after LCIS is 7.1% at 10 years.

A population-based study of racial and ethnic differences in survival among women with invasive cervical cancer: analysis of Surveillance, Epidemiology, and End Results data.

OBJECTIVE: The incidence of cervical cancer is higher in Hispanic than in non-Hispanic or African American women in the United States, but few studies have examined differences in survival between these groups. The objective of this study was to examine racial/ethnic differences in survival after diagnosis with invasive cervical cancer in a population-based sample of patients while adjusting for patient and tumor characteristics and treatment types. METHODS: We identified 7267 women (4431 non-Hispanic Caucasians, 1830 Hispanic Caucasians, and 1006 non-Hispanic African Americans) diagnosed with primary invasive cervical cancer from 1992 to 1996 (with follow-up through 2000) from the Surveillance, Epidemiology and End Results (SEER) Program. Kaplan-Meier and Cox proportional hazards survival methods were used to assess differences in survival by race/ethnicity. RESULTS: After adjusting for age at diagnosis, histology, stage, first course of cancer-directed treatment (surgery and radiation therapy), and SEER registry, Hispanic Caucasian women were at 26% decreased risk of death from any cause (hazard ratio (HR) = 0.74, 95% confidence interval (CI): 0.66-0.83) and non-Hispanic African American women were at 19% increased risk of death (HR = 1.19, 95% CI: 1.06-1.33) compared to non-Hispanic Caucasian women over the follow-up period. CONCLUSION: Analysis of population-based SEER data indicates significant survival differences by race/ethnicity for women with invasive cervical cancer. Hispanic Caucasian women in SEER had improved survival compared to non-Hispanic Caucasian or non-Hispanic African American women.

Design considerations for a computer controlled multileaf collimator for the Harper Hospital fast neutron therapy facility.

The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron is collimated using a unique multirod collimator (MRC). A computer controlled multileaf collimator (MLC) is being designed to improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. For the current study the use of focused or unfocused collimator leaves has been studied. Since the engineering effort associated with the leaf design and materials choice impacts significantly on cost, it was desirable to determine the clinical impact of using unfocused leaves in the MLC design. The MRC is a useful tool for studying the effects of using focused versus unfocused beams on beam penumbra. The effects of the penumbra for the different leaf designs on tumor and normal tissue DVHs in two selected sites (prostate and head and neck) was investigated. The increase in the penumbra resulting from using unfocused beams was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10 cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue in a prostate and head and neck case showed that the dosimetric disadvantages of using an unfocused rather than focused beam were minimal and only significant at shallow depths. For the rare cases, where optimum penumbra conditions are required, a MLC incorporating tapered leaves and, thus, providing focused collimation in one plane is necessary.

Sarcoma as a second malignancy after treatment for breast cancer.

BACKGROUND: Second malignant neoplasms may be a consequence of radiotherapy for the treatment of breast cancer. Prior studies evaluating sarcomas as second malignant neoplasms in breast cancer patients have been limited by the numbers of patients and relatively low incidence of sarcoma. Using data from the Surveillance, Epidemiology and End Results registries, we evaluated the influence of radiation therapy on the development of subsequent sarcomas in cases with primary breast cancer. METHODS: Cases with primary invasive breast cancer (n = 274,572) were identified in the Surveillance, Epidemiology and End Results Cancer Incidence Public-Use Database (1973-1997). The database was then queried to determine the cases developing subsequent sarcomas (n = 263). Eighty-seven of these cases received radiation therapy, and 176 had no radiation therapy. The cumulative incidence of developing secondary sarcoma and the survival post developing secondary sarcoma were determined by the Kaplan-Meier method. RESULTS: The occurrence of sarcoma was low, regardless of whether cases received or did not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per 1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis, respectively (p = 0.001). Of the sarcomas occurring within the field of radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of angiosarcomas occurring in cases not receiving radiotherapy. The cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases receiving radiation (SE = 0.2) and 0.1 per 1,000 for cases not receiving radiation (SE < 0.1). Overall survival was poor for cases of sarcoma after breast cancer (27-35% at 5 years), but not significantly different between patients receiving or not receiving radiation therapy for their primary breast cancer. CONCLUSIONS: Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma, but the magnitude of this risk is small. Angiosarcoma is significantly more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. The small difference in risk of subsequent sarcoma for breast cancer patients receiving radiotherapy does not supersede the benefit of radiotherapy.