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Alexandra L Hanlon

Publications and source records attributed to Alexandra L Hanlon.

At least 19 recordsLinked to original sources

Radiation dose and late failures in prostate cancer.

PURPOSE: To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone. METHODS: The data from 667 men with clinically localized intermediate- and high-risk prostate cancer treated with three-dimensional conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and BF, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median follow-up was 77 months. RESULTS: Multivariate analysis showed that increasing radiation dose was independently associated with decreased ASTRO BF (p < 0.0001), nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF occurred at < or =4 years after RT, and nadir + 2 BF was more evenly spread throughout Years 1-10, with 55% of BF in < or =4 years. Radiation dose escalation caused a shift in the BF from earlier to later years. The interval hazard function for DM appeared to be biphasic (early and late peaks) overall and for the <74-Gy group. In patients receiving > or =74 Gy, a reduction occurred in the risk of DM in the early and late waves, although the late wave appeared reduced to a greater degree. CONCLUSION: The ASTRO definition of BF systematically underestimated late BF because of backdating. Radiation dose escalation diminished and delayed BF; the delay suggested that local persistence may still be present in some patients. For DM, a greater radiation dose reduced the early and late waves, suggesting that persistence of local disease contributed to both.

Aged↗

The natural history of observed enhancing renal masses: meta-analysis and review of the world literature.

PURPOSE: Standard therapy for an enhancing renal mass is surgical. However, operative treatment may not be plausible in all clinical circumstances. Data on the natural history of untreated enhancing renal lesions is limited but could serve as a decision making resource for patients and physicians. We examined available data on the natural history of observed solid renal masses. MATERIALS AND METHODS: A Medline review of the literature was performed from 1966 to the present regarding untreated, observed, localized solid renal masses. To these data we added our institutional experience with a total of 61 lesions observed in 49 patients for a minimum of 1 year. Variables examined were initial lesion size at presentation, growth rate, duration of followup, pathological findings and progression to metastatic disease. Overall weighted mean estimates were calculated for lesion size at presentation, growth rate and followup based upon combining single institutional series with complete information. RESULTS: We identified 10 reports from 9 single institutional series in the world literature regarding the natural history of untreated solid localized renal lesions. The series included 6 to 40 patients (mean 25) with a mean followup of 30 months (range 25 to 39). When combined with our institutional data, a total of 286 lesions were analyzed, of which 234 could be included in the meta-analysis. Mean lesion size at presentation was 2.60 cm (median 2.48, range 1.73 to 4.08). Meta-analysis revealed a mean growth rate of 0.28 cm yearly (median 0.28, range 0.09 to 0.86) at a mean followup of 34 months (median 32, range 26 to 39) in all series combined. Pathological confirmation was available in 46% of the cases (131 of 286) and it confirmed 92% (120 of 131) as RCC variants. Evaluable data in this subset of confirmed RCC demonstrated a mean growth rate of 0.40 cm yearly (median 0.35, range 0.42 to 1.6). Lesion size at presentation did not predict the overall growth rate (p = 0.46). Progression to metastatic disease was identified in only 1% of lesions (3 of 286) during followup. CONCLUSIONS: The majority of small enhancing renal masses grow at a slow rate when observed. Although metastatic and cancer specific death are low, serial radiographic data alone are insufficient to predict the true natural history of these lesions. Therefore, physicians and patients assume a calculated risk when following these tumors. Basic biological data are needed to assess the natural history of untreated renal masses.

Disease Progression↗

Intensity modulated radiation therapy (IMRT) decreases acute skin toxicity for women receiving radiation for breast cancer.

OBJECTIVE: To determine the clinically observed incidence and severity of acute skin toxicity with breast intensity modulated radiation therapy (IMRT), and compare the results with a matched cohort of patients treated by conventional radiation therapy. Our hypothesis is that measures to decrease dose inhomogeneity within the breast and skin with IMRT will improve acute skin toxicity. MATERIALS AND METHODS: The study population consists of 73 women with early stage breast cancer treated with breast-conserving surgery and IMRT. The IMRT technique involves an iteration method for optimization to generate the IMRT plan, Monte Carlo dose calculation, and a step-and-shoot technique using multileaf collimation for beam delivery. Other aspects of the technique including the clinical definition of the clinical target volume by the physician, patient positioning, tangential beam orientation, dose and field sizes were unchanged compared conventional tangential radiation. These patients were matched one-to-one to a control group of 60 women treated with conventional photon radiation by using their bra size and chest wall separation. The study end point was acute skin toxicity. RESULTS: There were no observed differences in the acute toxicity based upon common terminology criteria for adverse events (CTC) for acute radiation dermatitis. There was no desquamation in 42% of IMRT patients, dry desquamation in 37% and moist desquamation in 21%. The degree of desquamation was greater for conventional patients compared with IMRT patients -52% grade 0, 10% grade 1, and 38% grade 2 (P = 0.001). Subgroup analysis showed desquamation was significantly lower with IMRT for small (P = 0.038) and large breast sizes (P = 0.037), but not medium sizes (P = 0.454). For large breast sizes, the incidence of moist desquamation grade 2 was 48% with IMRT compared with 79% in controls. Significant predictors of moist desquamation on stepwise logistic regression were use of IMRT (P = 0.0011) and breast size (P < 0.0001). CONCLUSIONS: IMRT is associated with a decrease in severity of acute desquamation compared with a matched control group treated with conventional radiation therapy. As with conventional radiation, breast size remains the most important prognostic factor for acute skin toxicity. The CTC grading system for acute radiation dermatitis is not sensitive when applied to modern breast cancer treatment because of its dependence of subjective rating of erythema and inability to gauge variations in desquamation. Further study of patient symptoms, quality of life, and cosmesis is needed to evaluate the benefit of IMRT for breast cancer.

Breast Neoplasms↗

A prostate specific antigen (PSA) bounce greater than 1.4 ng/mL Is clinically significant after external beam radiotherapy for prostate cancer.

OBJECTIVE: The purpose of this report is to determine whether any specific magnitude in the prostate specific antigen (PSA) bounce predicted for a clinically poorer outcome. METHODS AND MATERIALS: Between May 1989 and August 1999, 568 prostate cancer patients were treated with 3-dimensional conformal radiotherapy (RT). All patients had at least 5 years of follow up, 6 post-RT PSA measurements and received no hormonal therapy as part of their initial management. The median follow up was 85 months. The median RT dose was 74 Gy. A bounce was defined by a minimum rise in PSA of 0.4 ng/mL over a 6-month period, followed by a drop of PSA of any magnitude. The analysis of the optimal PSA bounce cut-point was based upon a recursive partitioning approach (RPA) for censored data using the log-rank test for nodal separation of freedom from biochemical failure (FFBF) as defined by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. Cox multivariate regression analysis (MVA) was used to confirm independent predictors of outcome among clinical and treatment related factors: PSA bounce as defined by the RPA, pretreatment PSA (continuous), Gleason score (2-6 versus 7-10), T stage (T1c/T2ab versus T2c/T3), and total radiation dose (continuous). RESULTS: There were 154 patients (27%) experienced a bounce with a median magnitude of 0.6. The RPA resulted in an optimal PSA bounce cut-point of 1.4 ng/mL such that 5-year Kaplan-Meier estimates of FFBF were 71%, 59%, and 38% for nonbouncers, a bounce < or =1.4 ng/mL and >1.4 ng/mL, respectively. Twenty-one (14%) of the 154 patients who experienced a bounce had a PSA bounce magnitude >1.4 ng/mL. Stepwise MVA demonstrated that the PSA bounce grouped as above was an independent predictor of FFBF (P = 0.0013), freedom from distant metastases (P = 0.0028) and cause specific survival (P = 0.0266). Lower RT dose (P < 0.0001) was the only independent predictor of a PSA bounce >1.4 ng/mL. CONCLUSIONS: Using recursive partitioning techniques, a clinically significant PSA bounce occurred when the magnitude of the bounce was >1.4 ng/mL. This is important information to aid clinicians in determining management after RT.

Aged↗

Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial.

PURPOSE: The alpha/beta ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. PATIENTS AND METHODS: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. RESULTS: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. CONCLUSION: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.

Dose Fractionation, Radiation↗

Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.

PURPOSE: To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. METHODS AND MATERIALS: From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. RESULTS: The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). CONCLUSION: The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.

Aged↗

Does a delay in external beam radiation therapy after tissue diagnosis affect outcome for men with prostate carcinoma?

BACKGROUND: Physicians involved in the care of men diagnosed with prostate carcinoma must assess the urgency of treatment. For those men who choose external beam radiation therapy (EBRT), the delay from the time of biopsy to treatment may be stressful. There are limited data on the consequences of radiation treatment delay. The purpose of the current study was to evaluate the effect of time to treatment (TTT) on outcomes. METHODS: The authors of the current study analyzed 1322 patients who were treated with EBRT alone. Overall survival (OS), cause specific survival (CSS), distant metastasis (DM), and freedom from biochemical failure (FFBF) were calculated. TTT was first analyzed at 4 intervals: < 3, 3-6, 6-9 and > 9 months, and at the median TTT. Cox multivariate analysis (MVA) was then performed with 2002 American Joint Commission on Cancer T-stage, Gleason score, prostate specific antigen (PSA), radiation dose, and TTT as covariates. RESULTS: There were no statistical differences in OS, CSS, DM, or FFBF among men whose EBRT began < 3, 3-6, 6-9, or > 9 months after diagnosis. This was also true at the median TTT of 3.1 months. A subgroup analysis was performed in which patients were stratified into low-, intermediate- and high-risk groups based on pretreatment PSA, Gleason score and AJCC T-stage. FFBF, and DM were calculated above and below the median TTT of 3.1 months. In this analysis, there was no statistically significant difference in FFBF or DM within the risk groups. CONCLUSIONS: Within the limits of the current study, data indicate that a treatment delay, even in high-risk patients, has little effect on clinical or biochemical outcome.

Adenocarcinoma↗

Long-term androgen deprivation increases Grade 2 and higher late morbidity in prostate cancer patients treated with three-dimensional conformal radiation therapy.

PURPOSE: To determine whether the use of androgen deprivation (AD) increases late morbidity when combined with high-dose three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Between May 1989 and November 1998, 1,204 patients were treated for prostate cancer with 3D-CRT to a median dose of 74 Gy. Patients were evaluated every 3-6 months. No AD was given to 945 patients, whereas 140 and 119 patients, respectively, received short-term AD (STAD; < or =6 months) and long-term AD (LTAD; > 6 months). Radiation morbidity was graded according to the Fox Chase modification of the Late Effects Normal Tissue Task Force late morbidity scale. Covariates in the multivariate analysis (MVA) included age, history of diabetes mellitus, prostate-specific antigen (PSA) level, Gleason score, T category, RT field size, total RT dose, use of rectal shielding, and AD status (no AD vs. STAD vs. LTAD). RESULTS: The only independent predictor for Grade 2 or higher genitourinary (GU) morbidity in the MVA was the use of AD (p = 0.0065). The 5-year risk of Grade 2 or higher GU morbidity was 8% for no AD, 8% for STAD, and 14% for LTAD (p = 0.02). Independent predictors of Grade 2 or higher gastrointestinal (GI) morbidity in the MVA were the use of AD (p = 0.0079), higher total radiation dose (p < 0.0001), the lack of a rectal shield (p = 0.0003), and older age (p = 0.0009). The 5-year actuarial risk of Grade 2 or higher GI morbidity was 17% for no AD vs. 18% for STAD and 26% for LTAD (p = 0.017). CONCLUSIONS: The use of LTAD seems to significantly increase the risk of both GU and GI morbidity for patients treated with 3D-CRT.

Aged↗

Pattern of local recurrence after conservative surgery and whole-breast irradiation.

PURPOSE: Most recurrences in the breast after conservative surgery and whole-breast irradiation have been reported to occur within the same quadrant as the initial primary tumor. We analyzed the long-term risk of recurrence by area of the breast after whole-breast irradiation. MATERIALS AND METHODS: In all, 1,990 women with Stage 0-II breast cancer were treated with conservative surgery and whole-breast irradiation from 1970-1998. Stage was ductal carcinoma in situ in 237, T1 in 1273, and T2 in 480 patients. Of 120 local recurrences, 71 were classified as true local (confined to the original quadrant) and 49 as elsewhere (involving outside the original quadrant). Kaplan-Meier methodology was used to calculate 5-year, 10-year, and 15-year rates of recurrence (95% confidence intervals in parentheses). The median follow-up is 80 months. RESULTS: There was no apparent difference in the 15-year rate of true local vs. elsewhere recurrence, but the time to recurrence was different. The rate of true local recurrence was 2%, 5%, and 7% (5-9%) at 5, 10, and 15 years, respectively. The recurrences elsewhere in the breast were rare at 5 (1%) and 10 (2%) years, but increased to 6 (3-9%) at 15 years. This 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers of 13% (10-16%). CONCLUSIONS: Recurrence elsewhere in the breast is rare for the first 10 years, but by 15 years is nearly equal to true local recurrence even after whole-breast irradiation. The 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers. This may indicate a therapeutic effect of whole-breast radiation for other areas of the breast. Very long follow-up will be needed for partial breast irradiation with or without tamoxifen to show that the risk of elsewhere recurrence is not significantly different than after whole-breast irradiation.

Adult↗

Biochemical failure and the temporal kinetics of prostate-specific antigen after radiation therapy with androgen deprivation.

PURPOSE: The accuracy of the American Society of Therapeutic Radiation Oncology consensus definition of biochemical failure (BF) after radiation therapy (RT) and androgen deprivation (AD) has been questioned, because posttreatment prostate-specific antigen (PSA) levels typically rise after release from AD, and misclassification of BF may be made. The temporal kinetics of posttreatment PSA levels was examined to define the error in the classification of BF. METHODS AND MATERIALS: Between December 1, 1991 and April 30, 1998, 688 men with T1c-T3 NX/0 M0 prostate cancer received three-dimensional conformal RT alone (n = 586) or in combination with either short-term (STAD: 3 to 12 months, n = 82) or long-term (LTAD: 12 to 36 months, n = 20) AD. Follow-up, calculated from the end of all treatment, was >/=48 months. The mean posttreatment PSA was calculated in 3-month intervals. RESULTS: The median posttreatment clinical follow-up period was 76 months (range, 48-152 months). The posttreatment PSA values from the end of all treatment for the RT+STAD-BF group showed an initial period of rise followed by a period of decline at 30 months and then a continued rise again. The decline in the mean posttreatment PSA is explained in part by stabilization in PSA level after 3 consecutive rises. Nonbiochemical failures (NBF) after RT+STAD had a relatively constant mean PSA over time of approximately 0.5 ng/mL. Unlike the RT+STAD-NBF profile, the RT+LTAD-NBF profile rose continuously and steadily to a level approaching 1 ng/mL. The RT+LTAD-BF profile rose continuously but at a slower rate over time. Nine RT+STAD-NBF patients (22%) and 2 RT+LTAD-BF (29%) patients experienced 3 consecutive rises followed by a subsequent decline and stabilization of PSA compared to 10 RT-BF patients (5%). Redistributing these misclassified patients to their respective NBF groups changed the mean posttreatment PSA profiles as follows: The RT+LTAD-BF profile rose constantly and steadily with a doubling time of approximately 16 months, and the RT+LAD-NF initially rose to a value of approximately 0.5 ng/mL, then at 36 months began to decline. CONCLUSIONS: The temporal kinetics of posttreatment PSA after RT+AD and RT alone are different. The American Society of Therapeutic Radiation Oncology definition for biochemical failure overestimates BF in 20-30% after RT+AD compared to 5% after RT alone.

Aged↗

What pretreatment prostate-specific antigen level warrants long-term androgen deprivation?

PURPOSE: Several large randomized prospective studies have demonstrated a survival benefit with the addition of long-term androgen deprivation to definitive radiotherapy for patients with Gleason score 8-10 or T3-T4 prostate cancer. However, these studies were performed before the routine use of prostate-specific antigen (PSA) measurement. The purpose of this study was to determine what pretreatment (initial) PSA (iPSA) level, if any, warrants the addition of long-term androgen deprivation in the PSA era. METHODS AND MATERIALS: The data set evaluated consisted of 1003 prostate cancer patients treated definitively with three-dimensional conformal radiotherapy between May 1, 1989 and November 30, 1999 (median follow-up, 61 months). Specifically excluded were patients with T3-T4 disease or Gleason score greater than 7 or those who had undergone androgen deprivation as a part of their initial therapy. The median radiation dose was 76 Gy. Patients were randomly split into two data sets, with the first (n = 487) used to evaluate the optimal iPSA cutpoint for which a statistically significant difference in outcome was noted. The second data set (n = 516) served as a validation data set for the initial modeling. The analysis of the optimal iPSA cutpoint was based on a recursive partitioning approach for censored data using the log-rank test for nodal separation of freedom from biochemical failure (FFBF) as defined by the American Society for Therapeutic Radiology and Oncology definition. Cox multivariate regression analysis was used to confirm independent predictors of outcome among the clinical and treatment-related factors: iPSA (grouped as defined by the recursive partitioning analysis), Gleason score (2-6 vs. 7), T stage (T1c-T2a vs. T2b-T2c), and total radiation dose (continuous). RESULTS: The recursive partitioning analysis data set resulted in an optimal iPSA cutpoint of 35 ng/mL, such that the 5-year Kaplan-Meier estimate of FFBF was 80%, 69%, and 19% for iPSA groups of 0-9.9, 10-35, and >35 ng/mL, respectively. The validation data set demonstrated the optimal iPSA cutpoint to be 30 ng/mL. Conservatively choosing 30 ng/mL as the optimal cutpoint, the 5-year FFBF estimate for the entire 1003 patients was 82%, 69%, and 20% for iPSA groups 0-9.9 (n = 630), 10-30 (n = 329), and >30 (n = 44) ng/mL, respectively. On multivariate regression analysis, with the iPSA grouped as above, the Gleason score and radiation dose were independent predictors of outcome in this patient group (all p < 0.001). On univariate analysis, a higher radiation dose improved FFBF when the iPSA level was between 10 and 30 ng/mL (p = 0.001) but not when the iPSA level was >30 or <10 ng/mL. CONCLUSION: Recursive partitioning techniques defined an iPSA cutpoint of 30 ng/mL for delineating intermediate vs. high risk. Patients with a PSA level >30 ng/mL in the absence of Gleason score >7 or T3 disease do poorly when treated with radiotherapy alone and should be considered for long-term androgen deprivation or other aggressive systemic therapy.

Aged↗

Role of prostate dose escalation in patients with greater than 15% risk of pelvic lymph node involvement.

PURPOSE: To determine whether the radiation dose is a determinant of clinical outcome in patients with a lymph node risk of >15% treated using whole pelvic (WP), partial pelvic (PP), or prostate only (PO) fields. METHODS AND MATERIALS: A total of 420 patients with prostate cancer treated with three-dimensional conformal radiotherapy with or without short-term androgen deprivation (STAD) between June 1989 and July 2000 were included in this study. Patients had an initial pretreatment prostate-specific antigen level of <100 ng/mL and a lymph node index of > or =15% or T2c tumors with a Gleason score of 6-10. No patient had radiologic evidence of lymph node involvement. Of the 460 patients, 48 were treated with PO, 74 with PP, and 298 with WP fields. The median prostate dose was 74 Gy for PO, 82 Gy for PP, and 76 Gy for WP. The median radiation dose to the pelvis was 46 Gy for both PP and WP. Of the 460 patients, 72 underwent STAD for a median of 3 months (range, 3-6 months). Cox regression multivariate analysis was used to identify independent predictors of freedom from biochemical failure (FFBF) defined according to the American Society for Therapeutic Radiology Oncology consensus guidelines. Univariate comparisons were done using the Kaplan-Meier method and the log-rank test. RESULTS: At a median follow-up of 43 months, 121 patients had treatment failure: 22, 7, and 92 in the PO, PP, and WP arms, respectively. Independent predictors of FFBF in multivariate analysis included radiation dose, T stage, Gleason score, and initial prostate-specific antigen level. The 5-year FFBF rate by dose group was 48% for <73 Gy, 64% for 73-76.9 Gy, and 74% for > or =77 Gy (p = 0.002). The use of STAD and radiation field size were not significantly associated with FFBF. CONCLUSION: The radiation dose was the most significant determinant of FFBF in patients with a lymph node risk >15% in the patient population studied. These data suggest that the primary tumor takes precedence over lymph node coverage or the use of STAD. Doses >70 Gy are of paramount importance in such intermediate- and high-risk patients.

Aged↗

The surgical management of superior sulcus tumors: a retrospective review with long-term follow-up.

BACKGROUND: We reviewed our experience with multimodality therapy for superior sulcus tumors to identify aspects of treatment that impact survival. METHODS: We retrospectively analyzed the records of 39 consecutive patients who underwent surgical resection in a single institution between 1993 and 2000. RESULTS: Median age at presentation was 59 years (range, 40 to 77). Twenty-five patients (64%) were men. At presentation, 36 patients (92%) had clinical T3 tumors and 3 (8%) had clinical T4 tumors. Mediastinoscopy was negative in all patients. Thirty-one patients (79%) received preoperative radiotherapy (median dose, 4500 cGy). Chemotherapy was administered concurrently with radiotherapy in 27 patients (69%). Complete surgical resection was performed in 34 patients (87%). There were 2 (5%) postoperative deaths. Of the 31 patients who received preoperative therapy, 14 (45%) had their tumors downstaged and 9 (29%) demonstrated a complete pathologic response. Median follow-up (100%) was 69 months. Overall 5-year survival was 47.9%. Five-year survival was 52.1% in patients with negative resection margins (p = 0.005), and 60.6% in patients who demonstrated a response to induction chemoradiation therapy (p = 0.008). Independently, margin status and response to induction therapy are predictors of overall survival (p = 0.01 and p = 0.02, respectively). Multivariable analysis identified margin status as the only factor significantly associated with overall survival. Negative margins strongly correlated with the response to preoperative therapy (p = 0.004). Disease-free survival correlated well with the response to induction therapy (p = 0.03). The chemotherapy regimen, T status, operative procedure, and complete pathologic response did not correlate with survival. CONCLUSIONS: The use of chemoradiation induction therapy may downstage tumors, enhance the ability to obtain a complete surgical resection, and prolong survival.

Adult↗

Importance of physical examination in the absence of a mammographic abnormality for the detection of early-stage breast cancer.

PURPOSE: A recent trial called into question the efficacy of breast self-examination. We studied the characteristics and outcome of women in whom physical examination (PE) was their sole method of breast cancer detection. PATIENTS AND METHODS: From 1970 to 1998, 1752 women with stage I/II breast cancer underwent breast-conserving surgery and radiation. Two hundred sixty patients (15%) had abnormal PE finding as their sole method of cancer detection at the time of diagnosis, 723 (41%) had only mammographic findings, and 762 (43%) had both. RESULTS: Detection by PE was associated with younger age, larger tumor size, positive axillary nodes, and use of chemotherapy. For women < 40 years of age, PE was the sole method of detection in 40% of cases. The patients for whom PE was the sole method of detection had equivalent 10-year locoregional control and overall survival (OS) compared with patients whose cancer was detected by mammography. Detection by PE was not an independent predictor for outcome on multivariate analysis. The use of tamoxifen (P = 0.0089) was the sole predictor for improved locoregional control. Tumor stage (P = 0.0001), nodal status (P = 0.039), age (P = 0.0112) and lymphovascular invasion (P = 0.0399) were negative predictors of OS. CONCLUSION: Although associated with younger age, larger tumors, and more frequent node positivity, in this study detection by PE did not confer worse outcome. This may be because of the increased use of chemotherapy in these patients. Physical examination remains an important method of detection of breast cancer, particularly for younger women for whom mammography is less sensitive and not performed as frequently.

Adult↗

The radiation doses to erectile tissues defined with magnetic resonance imaging after intensity-modulated radiation therapy or iodine-125 brachytherapy.

PURPOSE: To report penile bulb (PB) and corporal bodies (CB) doses during intensity-modulated radiation therapy (IMRT) and permanent (125)I prostate implant alone (BT) for favorable, early stage, clinically localized prostate cancer using computed tomography (CT) and magnetic resonance imaging (MRI) to provide a basis for comparison as the initial report of a comprehensive project to develop erectile tissues sparing techniques. METHODS AND MATERIAL: Prostate, PB and CB volumes were defined by a fused CT/MRI simulation study performed before treatment in 29 IMRT patients and verification study performed 30 days postimplant in 15 BT patients. The median prescribed prostate dose for the IMRT and BT groups was 74 Gy and 145 Gy, respectively. Dose volume histograms (DVHs) were generated to determine the dose characteristics for the PB, CB, and prostate for each patient. D(90), V(100), and V(50) were used, where D(i) was defined as the dose that covers i% of the prostate volume and V(i) is the fractional volume of the prostate that receives i% of the prescribed dose. The Wilcoxon rank sum test was used to evaluate significance between the groups. RESULTS: The median PB D(90), V(100), and V(50) values were 17.5 Gy, 0%, and 31.9% for the IMRT group; and 52.5 Gy, 21.5%, and 89.7% for the BT group. The median CB D(90), V(100), and V(50) values were 7.3 Gy, 0%, and 0.9% for the IMRT group; and 26.9 Gy, 2.4%, and 20.1% for the BT group. The differences between the IMRT vs. BT V(100) values, but not V(50), were statistically significant for the PB (p = 0.001) and CB (p = 0.001). CONCLUSIONS: Radiation dose to the PB and CB is low with IMRT or BT. Magnetic resonance imaging is superior to CT for the imaging of erectile tissues. Intensity-modulated radiation therapy may offer further reductions in the doses received by the PB and CB; however, at what cost to prostate coverage and normal tissue sparing will be the subject of a follow-up study.

Aged↗

Low complication rates are achievable after postmastectomy breast reconstruction and radiation therapy.

PURPOSE: To report our institution's experience of complications and cosmetic results among patients who underwent modified radical mastectomy followed by reconstruction and radiation therapy (RT). METHODS AND MATERIALS: Between 1987 and 2002, 85 patients with breast cancer underwent modified radical mastectomy, breast reconstruction, and postoperative RT. Reconstruction consisted of tissue expander/implant (TE/I) in 50 patients and an autologous transverse rectus abdominis myocutaneous (TRAM) flap in 35 patients. The primary end point of this study was the actuarial incidence of major and minor complications involving the reconstruction. Cosmesis was also assessed at each follow-up visit. RESULTS: The median follow-up from reconstruction was 28 months. The 5-year major complication rate was 0% in the TRAM group vs. 5% in the TE/I group (p = 0.21). The 5-year minor complication rate was 39% for the TRAM group vs. 14% for the TE/I group (p = 0.04). None (0%) of the TRAM complications required any corrective surgery, whereas 2 (33%) of the TE/I complications required implant removal. Of the TRAM patients with complications, 100% had superior cosmetic scores of excellent/good compared to only 17% of the TE/I patients who had complications (p = 0.003). Use of our custom-fashioned bolus resulted in a lower complication rate compared with standard bolus (p = 0.05). CONCLUSIONS: Patients treated with breast reconstruction and RT can experience a very low rate of major complications. We demonstrate no significant difference in the overall rate of major complications between TRAM and TE/I patients. Bolus can be safely used during postmastectomy RT with reconstruction, and we advocate the use of a custom wax bolus in the treatment of these patients. Postmastectomy RT should be considered in all eligible patients, even in the setting of reconstruction.

Adult↗

Soft tissue sarcomas treated with postoperative external beam radiotherapy with and without low-dose-rate brachytherapy.

PURPOSE: Patients treated for soft tissue sarcoma with adjuvant low-dose-rate brachytherapy (BT) plus external beam radiotherapy (EBRT) were compared with those treated with adjuvant EBRT alone. The hypothesis was that higher doses from postoperative BT plus EBRT would improve local tumor control. METHODS AND MATERIALS: The medical records of 130 sarcoma patients definitively treated between February 1983 and February 2001 were reviewed. Of these, 25 patients received BT followed by EBRT, and 61 were treated with EBRT alone. Overall survival, freedom from distant metastasis, and local control were calculated using Kaplan-Meier estimates. Univariate and multivariate analyses were performed. The mean postoperative radiation dose with EBRT alone was 59 Gy (range, 50-74) and 50 Gy (range, 40-70 Gy) when low-dose-rate BT was included. The mean implant dose was 16 Gy (range, 10-20 Gy). RESULTS: The 5-year Kaplan-Meier estimate for overall survival for BT plus EBRT and EBRT alone was 82% and 72% (p = 0.93), respectively. The 5-year freedom from distant metastasis and freedom from local failure rate for BT plus EBRT vs. EBRT alone was 90% vs. 78% (p = 0.15) and 90% vs. 83% (p = 0.25), respectively. In the univariate subset analysis, Stage III patients had better local control at 5 years (100% vs. 62%, p = 0.03) and a trend was noted for better local control for high-grade tumors (100% vs. 74%, p = 0.09) if treated with BT plus EBRT. No statistically significant predictors were found on multivariate analysis for local control. The median follow-up was 62 months. CONCLUSION: Local control at 5 years was high in both groups at 83% and 90%. On univariate analysis, Stage III patients had improved 5-year local control and a trend was found toward better local control for high-grade tumors. On multivariate analysis, no predictors were found for better local control; however, the numbers of Stage III and high-grade patients were small, which may have masked a possible benefit of BT plus EBRT in this population.

Adolescent↗