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Aims: Low-dose radiation therapy (LDRT) can increase biological efficacy of chemotherapy. This Phase II trial evaluates LDRT plus FOLFIRI-bevacizumab (FOLFIRI-B) in metastatic colorectal cancer.Materials& Methods: Primary Objective: raising the clinical complete response rate from 5 to 25%.Secondary Objectives: toxicity, progression-free survival. Patients underwent 12 FOLFIRI-B cycles plus two daily LDRT fractions (20 cGy/6 h interval) on each cycle. Statistical analysis was planned on 18 patients.Results: Results on 18 patients are reported. Specifically considering irradiated sites: 15/18 patients had a partial (11/18) or complete (4/18) response. Among 11 partial responders, three became a pathological CR after surgery. Grade 3-4 toxicity was recorded in two patients (11.1%). At median follow-up of 30 months (range: 8-50), 7/18 patients progressed in irradiated sites.Conclusion: Seven out of 18 patients (38.9%) had clinical or pathological CR in lesions treated with LDRT. Further studies on this newer treatment modality seem justified. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the expected time to prostate specific antigen (PSA) normalization with or without neoadjuvant androgen deprivation (NAAD) therapy after treatment with intensity modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer. Methods: A retrospective cohort research design was used. A total of 133 patients with clinical stage T1c to T3b prostate cancer (2002 AJCC staging) treated in a community setting between January 2002 and July 2005 were reviewed for time to PSA normalization using 1 ng/mL and 2 ng/mL as criteria. All patients received IMRT as part of their management. Times to PSA normalization were calculated using the Kaplan-Meier method. Significance was assessed at p < 0.05. Results: Fifty-six of the 133 patients received NAAD (42.1%). Thirty-one patients (23.8%) received radiation to a limited pelvic field followed by an IMRT boost, while 99 patients received IMRT alone (76.2%). The times to serum PSA normalization < 2 ng/mL when treated with or without NAAD were 298 ± 24 and 302 ± 33 days (mean ± SEM), respectively (p > 0.05), and 303 ± 24 and 405 ± 46 days, respectively, for PSA < 1 ng/mL (p < 0.05). Stage T1 and T2 tumors had significantly increased time to PSA normalization < 1 ng/mL in comparison to Stage T3 tumors. Also, higher Gleason scores were significantly correlated with a faster time to PSA normalization < 1 ng/mL. Conclusions: Use of NAAD in conjunction with IMRT leads to a significantly shortened time to normalization of serum PSA < 1 ng/mL in patients with clinically localized prostate cancer. [ABSTRACT FROM AUTHOR]

Cancer-related fatigue is a prevalent and debilitating condition that persists for years into survivorship. Studies evaluating both fish oil supplementation on fatigue and associations between fish oil consumption and fatigue have shown mixed effects; it is unknown what factors contribute to these differential effects. Herein, we investigate whether the nutritional status of cancer survivors was associated with serum omega-3 concentration or change in serum omega-3s throughout a fish oil supplementation study, and then if any of these factors were associated with fatigue. Breast cancer survivors 4–36 months post-treatment with moderate-severe fatigue were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g of each daily for 6 weeks. Baseline nutritional status was calculated using the Controlling Nutritional Status tool (serum albumin, lymphocytes, cholesterol). At baseline and post-intervention, serum fatty acids were quantified and fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Participants (n = 85) were 61.2 ± 9.7 years old with a body mass index of 31.9 ± 6.7 kg/m2; 69% had a good nutritional score and 31% had light-moderate malnutrition. Those with good nutritional status had greater total serum omega-3s at baseline (p = 0.013) and a greater increase in serum omega-3s with supplementation (p = 0.003). Among those who were supplemented with fish oil, greater increases in serum omega-3s were associated with greater improvements in fatigue. In conclusion, good nutritional status may increase uptake of fatty acid supplements, increasing their ability to improve fatigue. [ABSTRACT FROM AUTHOR]

Paratesticular malignant fibrous histiocytoma is an extremely rare malignancy of the scrotum. This malignancy has rarely been described in the literature and scant information exists on the optimal management of this cancer. We present here a case of a 57-year-old man with a diagnosis of high-grade malignant fibrous histiocytoma of the left intrascrotal region who underwent radical orchiectomy, systemic chemotherapy and postoperative radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of ≤ 3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes. [ABSTRACT FROM AUTHOR]

Purpose: NRG Oncology RTOG 9704 was the first adjuvant trial to validate the prognostic value of postresection CA19-9 levels for survival in patients with pancreatic carcinoma. The data resulting from this study also provide information about predictors of recurrence that may be used to tailor individualized management in this disease setting. This secondary analysis assessed the prognostic value of postresection CA19-9 and surgical margin status (SMS) in predicting patterns of disease recurrence., Methods and Materials: This multicenter cooperative trial included participants who were enrolled as patients at oncology treatment sites in the United States and Canada. The study included 451 patients analyzable for SMS, of whom 385 were eligible for postresection CA19-9 analysis. Postresection CA19-9 was analyzed at cut points of 90, 180, and continuously. Patterns of disease recurrence included local/regional recurrence (LRR) and distant failure (DF). Multivariable analyses included treatment, tumor size, and nodal status. To adjust for multiple comparisons, a P value of ≤ .01 was considered statistically significant and > .01 to ≤ .05 to be a trend., Results: For CA19-9, 132 (34%) patients were Lewis antigen-negative (no CA19-9 expression), 200 (52%) had levels <90, and 220 (57%) had levels <180. A total of 188 patients (42%) had negative margins, 152 (34%) positive, and 111 (25%) unknown. On univariate analysis, CA19-9 cut at 90 was associated with increases in LRR (trend) and DF. Results were similar at the 180 cut point. SMS was not associated with an increase in LRR on univariate or multivariate analyses. On multivariable analysis, CA19-9 ≥ 90 was associated with increased LRR and DF. Results were similar at the 180 cut point., Conclusions: In this prospective evaluation, postresection CA19-9 was a significant predictor of both LRR and DF, whereas SMS was not. These findings support consideration of adjuvant radiation therapy dose intensification in patients with elevated postresection CA19-9.

Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases., Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded., Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%)., Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients., Methods: Patients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria., Results: Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level., Conclusions: An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.

Background: Radiotherapy (RT) is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV) in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI) in the preoperative and definitive treatment of pancreatic cancer., Methods: The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries., Results: We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided., Conclusions: The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

Objectives: To evaluate the feasibility of intensity-modulated radiotherapy with simultaneous integrated boost to the dominant intraprostatic lesion for definitive treatment of prostate cancer., Materials and Methods: Patients were deemed eligible for the study if they had histologically proven stage cT2-T3 N0M0 prostate adenocarcinoma. In addition <20% risk of lymph nodal involvement according to Roach formula, was required for enrollment. Patients were treated with intensity-modulated radiotherapy with simultaneous integrated boost technique to the dominant intraprostatic lesion defined by magnetic resonance imaging. The prescribed dose to the prostate and seminal vesicles was 72 Gy (1.8 Gy per fraction). The dose delivered to the intraprostatic lesion received was 80 Gy (2 Gy per fraction). Acute gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated weekly during treatment, and at 1 and 3 months thereafter. Late GI and GU toxicity was evaluated by Kaplan Meier method., Results: Forty patients were deemed evaluable. Acute and late GI and GU toxicity were evaluated in all patients. Two patients (5%) developed acute grade 3 GI toxicity and 1 patient (2.5%) developed acute grade 3 GU toxicity. No grade 4 acute GI or GU toxicity occurred. With a median follow-up of 19 months (interquartile range, 15 to 26 mo), the 2-year actuarial cumulative incidence of grade ≥2 rectal toxicity was 9.5%. The 2-year actuarial cumulative incidence of grade ≥2 urinary toxicity was 13.3%., Conclusions: Treatment related acute toxicity was low in our cohort. Prolonged observation with a larger series of patients is necessary to evaluate late toxicity and local control.

The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT., (Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

A 77-year-old male patient with unresected malignant pleural mesothelioma, clinical stage T3N0M0 according to the New International Staging System for Diffuse Malignant Pleural Mesothelioma, received intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) after 6 cycles of chemotherapy with cisplatin and pemetrexed. SIB-IMRT delivered 40.5 Gy (1.5 Gy/fraction) to the left pleura and 50 Gy (1.85 Gy/fraction) to the sites of macroscopic disease. Radiotherapy was well tolerated. Two months after the end of radiotherapy the patient showed grade 2 lung toxicity (febrile episodes accompanied by dry cough) that was successfully treated with steroid therapy. Local control lasted for 2 years after SIB-IMRT. Then the tumor recurred marginally to the radiation field and the patient underwent chemotherapy with pemetrexed. Three years from the diagnosis, the patient is alive and in good general condition. He only takes prednisone 5 mg/daily for exertional dyspnea. To the best of our knowledge this is the first reported use of SIB-IMRT in unresected malignant pleural mesothelioma. Considering the dosimetric advantages of SIB-IMRT and the clinical results observed in our patient, additional evaluation of this technique seems justified.

We evaluated a step-and-shoot IMRT plan in the postoperative irradiation of the vaginal vault compared with equispaced beam arrangements (3-5) 3D-radiotherapy (RT) optimized plans. Twelve patients were included in this analysis. Four plans for each patient were compared in terms of dose-volume histograms, homogeneity index (HI), and conformity index (CI): (1) 3 equispaced beam arrangement 3D-RT; (2) 4 equispaced beam arrangement 3D-RT; (3) 5 equispaced beam arrangement 3D-RT; (4) step-and-shoot IMRT technique. CI showed a good discrimination between the four plans. The mean scores of CI were 0.58 (range: 0.38-0.67) for the 3F-CRT plan, 0.58 (range: 0.41-0.66) for 4F-CRT, 0.62 (range: 0.43-0.68) for 5F-CRT and 0.69 (range: 0.58-0.78) for the IMRT plan. A significant improvement of the conformity was reached by the IMRT plan (p < 0.001 for all comparisons). As expected, the increment of 3D-CRT fields was associated with an improvement of target dose conformity and homogeneity; on the contrary, in the IMRT plans, a better conformity was associated to a worse target dose homogeneity. A significant reduction in terms of D(mean), V90%, V95%, V100% was recorded for rectal and bladder irradiation with the IMRT plan. Surprisingly, IMRT supplied a significant dose reduction also for rectum and bladder V30% and V50%. A significant dosimetric advantage of IMRT over 3D-RT in the adjuvant treatment of vaginal vault alone in terms of treatment conformity and rectum and bladder sparing is shown., (2010 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the technical feasibility of utilizing the Active Breathing Coordinator for planning of postoperative three-dimensional conformal radiation therapy in patients with early stage breast cancer undergoing breast conservation therapy., Methods: Patients with early stage breast cancer for whom adjuvant radiotherapy after breast-conserving surgery was planned were consecutively enrolled. Five sessions of simulation with the Active Breathing Coordinator were planned for each patient. Computed tomography for simulation was not acquired until a good level of compliance with the procedure was achieved by the patient. Patients who did not show a satisfactory level of compliance after the planned fifth session were defined as noncompliant. Two simulation computed tomography scans were acquired: the first without the Active Breathing Coordinator during free breathing, the second with the Active Breathing Coordinator. Forward intensity-modulated treatment plans were calculated. Mean lung dose (MLDipsilateral) and V30 (V30lung) for the ipsilateral lung and V30 for the heart (V30heart), were evaluated., Results: Twenty consecutive patients were enrolled (6 with left-sided breast cancer and 14 with right-sided breast cancer). Eighteen of the patients completed the simulation computed tomography with the Active Breathing Coordinator after 1-5 sessions (median, 3). In 16 of the 18 patients, a reduction of V301ung was observed with the Active Breathing Coordinator. In 15 of the 18 patients, a reduction of MLDipsiateral was also observed. In 5 of the 6 patients with left-sided breast cancer, a reduction of V30heart was noted., Conclusions: Routine application of the Active Breathing Coordinator in clinical practice is feasible, even though it requires an increased workload. Dosimetric results are encouraging in terms of a better sparing of the ipsilateral lung and the heart.

Purpose: To determine the maximum tolerated dose of short-course radiotherapy (intensity-modulated radiotherapy technique) to the upper two thirds of the vagina in endometrial cancers with low risk of local recurrence., Patients and Methods: A Phase I clinical trial was performed. Eligible patients had low-risk resected primary endometrial adenocarcinomas. Radiotherapy was delivered in 5 fractions over 1 week. The planning target volume was the clinical target volume plus 5 mm. The clinical target volume was defined as the upper two thirds of the vagina as evidenced at CT simulation by a vaginal radio-opaque device. The planning target volume was irradiated by a seven-field intensity-modulated radiotherapy technique, planned by the Plato Sunrise inverse planning system. A first cohort of 6 patients received 25 Gy (5-Gy fractions), and a subsequent cohort received 30 Gy (6-Gy fractions). The Common Toxicity Criteria scale, version 3.0, was used to score toxicity., Results: Twelve patients with endometrial cancer were enrolled. Median age was 58 years (range, 49-74 years). Pathologic stage was IB (83.3%) and IC (16.7%). Median tumor size was 30 mm (range, 15-50 mm). All patients completed the prescribed radiotherapy. No patient experienced a dose-limiting toxicity at the first level, and the radiotherapy dose was escalated from 25 to 30 Gy. No patients at the second dose level experienced dose-limiting toxicity. The most common Grade 2 toxicity was gastrointestinal, which was tolerable and manageable., Conclusions: The maximum tolerated dose of short-course radiotherapy was 30 Gy at 6 Gy per fraction. On the basis of this result, we are conducting a Phase II study with radiotherapy delivered at 30 Gy.

Purpose: To examine the relationship between tumor regression grade (TRG) and outcomes in patients with rectal cancer treated with preoperative therapy., Methods and Materials: Specimens from 144 patients with cT3,4 rectal cancer who had received preoperative radiation +/- chemotherapy and had a minimum follow-up of 3 years were retrospectively reviewed. TRG, which involves examining the residual neoplastic cells and scoring the degree of both cytological changes, including nuclear pyknosis or necrosis and/or eosinophilia, as well as stromal changes, including fibrosis (either dense or edematous) with or without inflammatory infiltrate and giant-cell granulomatosis around ghost cells and keratin, was quantified in five grades according to the Mandard score (Cancer 1994;73:2680-2686). The greater the response, the lower the TRG score. The median follow-up was 72 months (range, 40-143 months)., Results: Of the 144 patients, 19% were TRG1, 12% were TRG2, 21% were TRG3, 46% were TRG4, and 1% were TRG5. To simplify the analysis, TRG was combined into two groups: TRG1-2 and TRG3-5. By univariate analysis, none of the pretreatment factors examined, including age, circumference, length, distance from the anorectal ring, pretreatment T and N stage, and INDpre (defined as the pretreatment reference index size based on digital rectal examination), had an impact on 5-year outcomes, including local control, metastases-free survival, disease-free survival, and overall survival. Postoperative parameters, including pathologic T stage (pT), pathologic N stage (pN), and TRG, did significantly influence 5-year outcomes. These included local failure: pT0-2: 5% vs. pT3-4: 19%, p = 0.007; pN0: 7% vs. pN1-3: 26%, p = 0.002; TRG1-2: 2% vs. TRG3-5: 17%, p = 0.013; metastasis-free survival: pT0-2: 86% vs. pT3-4: 62%, p = 0.005; pN-: 86% vs. pN*: 42%, p < 0.001; TRG1-2: 91% vs. TRG3-5: 66%, p = 0.004; disease-free survival: pT0-2: 83% vs. pT3-4: 54%, p = 0.001; pN0: 80% vs. pN1-3: 39%, p < 0.001; TRG1-2: 91% vs. TRG3-5: 58%, p < 0.001; and overall survival: pT0-2: 85% vs. pT3-4: 65%, p = 0.007; pN0: 86% vs. pN1-3: 45%, p < 0.001; TRG1-2: 89% vs. TRG3-5: 68%, p = 0.004. By multivariate analysis combining all pre- and posttreatment parameters, only pN (p < 0.001) and TRG (p = 0.005) significantly predicted disease-free survival. Furthermore, TRG predicted the incidence of pathologic nodal involvement (p < 0.0001)., Conclusions: By univariate analysis, TRG is a predictor for local failure, metastases-free survival, and overall survival. By multivariate analysis, it predicts improved disease-free survival. Given the ability of TRG to predict those patients with N* disease, it may be helpful, in combination with other clinicopathologic factors, in selecting patients for a more conservative procedure, such as local excision rather than radical surgery, after preoperative therapy.

Purpose: To determine the expected time to serum testosterone normalization after short-course neoadjuvant androgen deprivation therapy (NAAD) and three-dimensional conformal radiotherapy for patients with localized prostate cancer and to identify pretreatment predictors that correlated with the time to testosterone normalization., Methods: Between 1993 and 1999, 88 patients with localized prostate cancer, treated with NAAD and external beam radiotherapy, were prospectively monitored after treatment with sequential testosterone levels. NAAD was administered before and during the entire course of radiotherapy and discontinued at the end of treatment. The median duration of NAAD was 6 months. The actuarial rate of serum testosterone normalization from the end of treatment was evaluated, and the presence or absence of androgen deprivation-related symptoms was correlated with serum testosterone levels. Symptoms assessed included weight gain, loss of libido, breast tenderness, breast enlargement, hot flashes, and fatigue., Results: Serum testosterone levels returned to the normal range in 57 (65%) of the 88 patients and failed to normalize in 31 patients (35%). The median time to normalization was 18.3 months. The actuarial rate of normalization at 3, 6, 12, and 24 months was 10%, 26%, 38%, and 59%, respectively. In a multivariate analysis, a pretreatment testosterone level in the lower range of normal was the only variable that predicted for delayed testosterone normalization after NAAD (p = 0.00047). Among 45 patients with information concerning androgen deprivation-related symptoms recorded 1 year after cessation of NAAD, 24 (53%) had normalized testosterone levels, but in 21 patients (47%), the levels had not yet returned to normal. At 1 year, only 1 (4%) of 24 patients whose testosterone level had returned to normal experienced NAAD-related symptoms compared with 14 (67%) of 21 patients who did not have normal testosterone levels (p <0.001)., Conclusion: Testosterone levels often remain depressed for extended periods after cessation of short-course NAAD. Lower baseline testosterone levels predict for a delay in testosterone normalization, and the persistence of symptoms related to androgen deprivation correlates with low testosterone levels.