Biomedical subjects

Vivian Weinberg

Publications and source records attributed to Vivian Weinberg.

At least 19 recordsLinked to original sources

PubMed2007

Staging for prostate cancer: time to incorporate pretreatment prostate-specific antigen and Gleason score?

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system for prostate cancer is based primarily based on clinical tumor (T) classification. In this article, the authors summarize arguments for incorporating additional pretreatment parameters and creating a new staging system for prostate cancer. METHODS: Men with localized prostate cancer who received treatment with external beam radiation alone were analyzed using the 1997 AJCC staging system compared with a system that included pretreatment prostate-specific antigen (pPSA) level and Gleason score (GS). Multivariate analyses using a Cox proportional-hazards model were carried out to evaluate T classification, GS, and pPSA as predictors of overall survival (OS), disease-specific survival (DSS), and freedom from PSA failure (FFPF). RESULTS.: Based on pretreatment characteristics in a series of contemporary patients, only 0.6% of patients were classified with AJCC stage I disease, 16.0% were classified with AJCC stage III disease, and 83.4% were classified with AJCC stage II disease. Multivariate analyses indicated the independent statistical significance of T classification, GS, and pPSA in predicting OS, DSS, and FFPF (model chi-square value, P < .0001 for each). Using these 3 predictors, subsets of patients who had similar outcomes were combined to provide examples of the insensitivity of the AJCC system for predicting outcomes. Incorporating pPSA and GS allowed the identification of differences in OS, DSS, and FFPF for subsets of patients with AJCC stage II disease (P < .0001, P = .005, and P < .0001, respectively). CONCLUSIONS: The current AJCC staging system does not divide contemporary patients with prostate cancer into prognostic subgroups and does not identify patients who have comparable biochemical control and survival. The AJCC staging system for prostate cancer should be changed to incorporate pPSA, GS, and risk stratification.

Antineoplastic Agents, Hormonal↗

PubMed2006

Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: the University of California-San Francisco experience.

PURPOSE: The aim of this study was to evaluate the feasibility and safety of salvage high-dose-rate (HDR) brachytherapy for locally recurrent prostate cancer after external beam radiotherapy (EBRT). METHODS AND MATERIALS: We retrospectively analyzed 21 consecutively accrued patients undergoing salvage HDR brachytherapy for locally recurrent prostate cancer after EBRT between November 1998 and December 2005. After pathologic confirmation of locally recurrent disease, all patients were treated with 36 Gy in six fractions using two transrectal ultrasound-guided HDR prostate implants, separated by 1 week. Eleven patients received neoadjuvant hormonal therapy immediately presalvage, whereas none received adjuvant hormonal therapy postsalvage. Median follow-up time from recurrence was 18.7 months (range, 6-84 months). Determination of subsequent biochemical failure after brachytherapy was based on the definition by the American Society for Therapeutic Radiology and Oncology. RESULTS: Based on the Common Terminology Criteria for Adverse Events (CTCAE version 3), 18 patients reported Grade 1 to 2 genitourinary symptoms by 3 months postsalvage. Three patients developed Grade 3 genitourinary toxicity. Maximum observed gastrointestinal toxicity was Grade 2; all cases spontaneously resolved. The 2-year Kaplan-Meier estimate of biochemical control after recurrence was 89%. Thirteen patients have achieved a PSA nadir < or =0.1 ng/ml, but at the time of writing this endpoint has not yet been reached for all patients. All patients are alive; however 2 have experienced biochemical failure, both with PSA nadirs > or =1, and have subsequently been found to have distant metastases. CONCLUSIONS: Salvage HDR prostate brachytherapy appears to be feasible and effective.

Aged↗

PubMed2006

Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence.

PURPOSE: This study sought to review a single-institution experience with the management of adenoid cystic carcinoma of the head and neck. METHODS AND MATERIALS: Between 1960 and 2004, 140 patients with adenoid cystic carcinoma of the head and neck were treated with definitive surgery. Ninety patients (64%) received postoperative radiation to a median dose of 64 Gy (range, 54-71 Gy). Distribution of T stage was: 26% T1, 28% T2, 20% T3, and 26% T4. Seventy-eight patients (56%) had microscopically positive margins. Median follow-up was 66 months (range, 7-267 months). RESULTS: The 5- and 10-year rate estimates of local control were 88% and 77%, respectively. A Cox proportional hazards model identified T4 disease (p = 0.0001), perineural invasion (p = 0.008), omission of postoperative radiation (p = 0.007), and major nerve involvement (p = 0.02) as independent predictors of local recurrence. Radiation dose lower than 60 Gy (p = 0.0004), T4 disease (p = 0.005), and major nerve involvement (p = 0.02) were predictors of local recurrence among those treated with surgery and postoperative radiation. The 10-year overall survival and distant metastasis-free survival were 64% and 66%, respectively. CONCLUSION: Combined-modality therapy with surgery followed by radiation to doses in excess of 60 Gy should be considered the standard of care for adenoid cystic carcinoma of the head and neck.

Adolescent↗

PubMed2006

Clinical response to therapy targeted at vascular endothelial growth factor in metastatic renal cell carcinoma: impact of patient characteristics and Von Hippel-Lindau gene status.

OBJECTIVE: To describe the relationship among patient characteristics, Von Hippel-Lindau (VHL) gene status and clinical outcome in metastatic renal cell carcinoma (RCC) in patients receiving vascular endothelial growth factor (VEGF)-targeted therapy. PATIENTS AND METHODS: All patients with metastatic RCC who received therapy with interferon-alpha plus bevacizumab, SU11248 or AG013736 at the authors' institution were considered. Clinical features were collected and activation status of the VHL gene (VHL) was determined from baseline paraffin-embedded tumour samples. Tumour response, time to tumour progression (TTP) and overall survival were recorded. RESULTS: Forty-three patients were evaluable for determination of VHL status and clinical response. There was an objective response in 18 patients (43%; 95% confidence interval 28-59%). The median TTP for the entire cohort was 8.1 months. There was an improved clinical outcome in patients with the following clinical features: male gender, lack of hepatic metastases, no previous radiation therapy and higher baseline haemoglobin level. Twenty-six patients (60%) had evidence of VHL mutation or promoter methylation; such patients had an objective response rate of 48%, vs 35% in patients with no VHL mutation or methylation. Patients with VHL methylation or a mutation predicted to truncate or shift the VHL reading frame had a median TTP of 13.3 months, vs 7.4 months in patients with none of these features (P = 0.06). CONCLUSION: VEGF-targeted therapy is active in metastatic RCC and the response can be associated with certain clinical features. The TTP with VEGF-targeted therapy might be prolonged in patients with VHL methylation or mutations that truncate or shift the VHL reading frame. Further investigation of VHL pathway components is needed to understand the biology of the response to VEGF-targeted agents in metastatic RCC.

Adult↗

PubMed2006

Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy.

BACKGROUND: APC8015 (sipuleucel-T) is a cellular prostate cancer vaccine containing autologous antigen-presenting cells (APC) loaded with PA2024, a recombinant prostatic acid phosphatase/granulocyte-macrophage-colony-stimulating factor fusion protein, as the immunogen. Bevacizumab is a recombinant antibody against vascular endothelial growth factor, a proangiogenic protein with inhibitory effects on APC. A clinical trial was conducted to determine the prostate-specific antigen (PSA) and immunomodulatory effects of this combination immunotherapy. METHODS: Patients with androgen-dependent prostate cancer who had received prior definitive therapy with nonmetastatic, recurrent disease as manifested by a rising PSA of between 0.4 ng/mL and 6.0 ng/mL were enrolled. APC8015 was given intravenously(i.v.) on Weeks 0, 2, and 4. Bevacizumab was given at a dose of 10 mg/kg i.v. on Weeks 0, 2, 4, and every 2 weeks thereafter until toxicity or disease progression. PSA changes were recorded and the PSA doubling time (PSADT) was calculated. Immune response versus PA2024 was measured at baseline and after treatment by T-cell proliferation and interferon-gamma enzyme-linked immunospot (ELISPOT) assays. RESULTS: Twenty-two patients were treated. One patient achieved a > or =50% decrease in PSA. Nine patients exhibited some decrease in PSA from baseline, ranging from 6% to 72%, with the PSA of 3 patients decreasing at least 25%. The median pretreatment PSADT for the 20 evaluable patients was 6.9 months and the median posttreatment PSADT was 12.7 months (P = .01). All patients demonstrated induction of an immune response against PA2024. CONCLUSIONS: The combination of APC8015 and bevacizumab induces an immune response and modulates PSA in patients with biochemically recurrent prostate cancer.

Acid Phosphatase↗

PubMed2006

Three-dimensional conformal external beam radiotherapy compared with permanent prostate implantation in low-risk prostate cancer based on endorectal magnetic resonance spectroscopy imaging and prostate-specific antigen level.

PURPOSE: To evaluate the metabolic response by comparing the time to resolution of spectroscopic abnormalities (TRSA) and the time to prostate-specific antigen level in low-risk prostate cancer patients after treatment with three-dimensional conformal external beam radiotherapy (3D-CRT) compared with permanent prostate implantation (PPI). Recent studies have suggested that the treatment of low-risk prostate cancer yields similar results for patients treated with 3D-CRT or PPI. METHODS AND MATERIALS: A total of 50 patients, 25 in each group, who had been treated with 3D-CRT or PPI, had undergone endorectal magnetic resonance spectroscopy imaging before and/or at varying times after therapy. The 3D-CRT patients had received radiation doses of > or =72 Gy compared with 144 Gy for the PPI patients. The spectra from all usable voxels were examined for detectable levels of metabolic signal, and the percentages of atrophic and cancerous voxels were tabulated. RESULTS: The median time to resolution of the spectroscopic abnormalities was 32.2 and 24.8 months and the time to the nadir prostate-specific antigen level was 52.4 and 38.0 months for the 3D-CRT and PPI patients, respectively. Of the 3D-CRT patients, 92% achieved negative endorectal magnetic resonance spectroscopy imaging findings, with 40% having complete metabolic atrophy. All 25 PPI patients had negative endorectal magnetic resonance spectroscopy imaging findings, with 60% achieving complete metabolic atrophy. CONCLUSION: The results of this study suggest that metabolic and biochemical responses of the prostate are more pronounced after PPI. Our results have not proved PPI is more effective at curing prostate cancer, but they have demonstrated that it may be more effective at destroying prostate metabolism.

Aged↗

PubMed2006

Maximal COX-2 immunostaining and clinical response to celecoxib and interferon alpha therapy in metastatic renal cell carcinoma.

BACKGROUND: Cyclooxygenase-2 (COX-2) plays a major role in the development of cancer through numerous mechanisms. COX-2 is expressed in the majority of renal cell carcinoma (RCC) tumors and correlates with stage, grade, and microvessel density. Based on potential additive or synergistic antitumor effects, interferon-alpha (IFNalpha) and celecoxib, an oral COX-2 inhibitor, were given to metastatic RCC patients in a Phase II trial. METHODS: Patients with untreated, metastatic RCC received IFNalpha 3 million units (MU) daily and celecoxib 400 mg orally (p.o.) twice daily continuously until disease progression or unacceptable toxicity. Pretreatment, paraffin-embedded RCC tumor samples were immunohistochemically stained for COX-2 expression and plasma basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were assayed to determine predictive or prognostic potential. RESULTS: There were three partial responses among 25 patients treated (objective response rate, 12%; 95% confidence interval [CI], 3-31%). The observed median time to disease progression (TTP) for the entire cohort was 3.3 months. A significant association between maximal COX-2 staining and clinical response was observed: all patients who experienced an objective response demonstrated 3+ COX-2 tumor immunostaining (trend test: P=0.03). Therapy was well tolerated without cardiac or other notable toxicity. CONCLUSIONS: The addition of celecoxib to IFNalpha did not increase the objective response rate or TTP of this unselected cohort. Maximal COX-2 tumor immunostaining may identify RCC patents more likely to achieve clinical benefit with COX-2 inhibition in combination with IFNalpha. Further investigation of this combination in 3+ COX-2-overexpressing RCC tumors is warranted.

Administration, Oral↗

PubMed2006

Estimates of ocular and visual retention following treatment of extra-large uveal melanomas by proton beam radiotherapy.

OBJECTIVE: To assess outcomes of proton beam radiotherapy for the treatment of extra-large uveal melanomas in patients specifically referred to the University of California, San Francisco, for ocular conservation therapy. Series patients uniformly refused enucleation both at an outside institution and again as a treatment option after extensive discussion at the University of California, San Francisco. DESIGN: In a retrospective, nonrandomized cohort study, 21 patients with extra-large choroidal or ciliochoroidal melanomas measuring at least 10 mm in maximum thickness or 20 mm in maximum basal diameter or tumors located within 3 mm of the optic nerve measuring at least 8 mm in maximum thickness or 16 mm in maximum basal diameter met inclusion criteria. Main outcome measures were frequency of (1) anterior segment complications (lash loss, keratopathy, cataract, and neovascular glaucoma), (2) posterior segment complications (vitreous hemorrhage, radiation retinopathy, and radiation papillopathy), (3) treatment failure (tumor growth, enucleation, or metastases), and (4) final visual acuity. RESULTS: Median follow-up was 28 months. Mean age at treatment was 58.3 years. The frequencies of hypertension and diabetes mellitus were 14.3% and 9.5%, respectively. Mean tumor thickness and mean basal diameter were 8.6 mm and 18.7 mm, respectively. Lash loss occurred in 52.4%; dry eye, in 23.8%; cataract, in 28.6%; neovascular glaucoma, in 38.1% (100% in patients with diabetes mellitus); radiation retinopathy, in 9.5%; and radiation papillopathy, in 9.5%. No patient developed radiation-associated scleral necrosis or vitreous hemorrhage. The 2-year Kaplan-Meier estimate of local tumor growth after treatment was 33%, and the rate of distant metastasis was 10%. Visual acuity of 20/200 or better was preserved in 25% of patients, including 4 patients (19%) who experienced an average of 4 lines of Snellen visual acuity improvement. Development of neovascular glaucoma was associated with tumors in close proximity to the optic nerve (P = .04), while cataract (P = .03) and lash loss (P = .02) occurred with more anteriorly located tumors. Proton beam radiotherapy provided a 67% probability of local control and 90% probability of clinically discernible metastases-free survival at 24 months after treatment. CONCLUSION: Proton beam radiotherapy is an ocular-conserving option that may be considered for the treatment of extra-large uveal melanoma in carefully selected patients.

Adult↗

PubMed2006

Clinical and immunological characteristics of patients with serologic progression of prostate cancer achieving long-term disease control with granulocyte-macrophage colony-stimulating factor.

PURPOSE: We describe the clinical and immunological characteristics of patients with biochemically relapsed prostate cancer who achieved long-term disease control with GM-CSF (Leukine). MATERIALS AND METHODS: A total of 30 patients with prostate cancer and nonmetastatic recurrent disease, as manifested by increasing PSA between 0.4 and 6.0 ng/ml after prior definitive therapy, were enrolled in a phase II trial. Patients received 250 microg/m2 GM-CSF daily subcutaneously on days 1 through 14 of a 28-day cycle until PSA or objective progression. The patient and disease characteristics of patients who remained without evidence of disease progression beyond 4 years were examined. Additionally, flow cytometry was performed in peripheral blood to characterize monocyte and dendritic cells. RESULTS: Seven of 29 evaluable patients (24%) remained free of disease progression at a median of 5.1 years (range 4.5 to 5.6 or greater) from the start of GM-CSF therapy. Patients on long-term GM-CSF tended to have lower initial T stage, Gleason score and pretreatment PSA. An increase in the number of circulating monocytes and dendritic cells was observed after 14 days of GM-CSF treatment. These values returned to baseline during the 14-day off period. CONCLUSIONS: GM-CSF modulates PSA in androgen dependent, biochemically relapsed cases. A substantial proportion of patients achieve long-term disease control. The clinical characteristics described may help select patients for future clinical trials with GM-CSF or other immunomodulators. Additional investigation is required to define the immunological mechanism of GM-CSF in prostate cancer.

Aged↗

PubMed2006

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy.

OBJECTIVE: To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. PATIENTS AND METHODS: Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. RESULTS: In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. CONCLUSIONS: Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.

Aged↗

PubMed2006

Clinical outcomes of intraoperative radiation therapy for extremity sarcomas.

Purpose. Radiation of extremity lesions, a key component of limb-sparing therapy, presents particular challenges, with significant risks of toxicities. We sought to explore the efficacy of intraoperative radiation therapy (IORT) in the treatment of soft tissue sarcomas of the extremities. Patients. Between 1995 and 2001, 17 patients received IORT for soft tissue sarcomas of the extremities. Indications for IORT included recurrent tumors in a previously radiated field or tumors adjacent to critical structures. Results. Gross total resections were achieved in all 17 patients. Two patients experienced locoregional relapses, six patients recurred at metastatic sites, and one patient died without recurrence. Thirty-six month estimates for locoregional control, disease free survival, and overall survival were 86%, 50%, and 78%, respectively. IORT was extremely well tolerated, with no toxicities referable to IORT. Conclusions. For patients with soft tissue sarcomas of the extremities, IORT used as a boost to EBRT provides excellent local control, with limited acute toxicities.

Journal Article↗

PubMed2005

Repeat CT imaging and replanning during the course of IMRT for head-and-neck cancer.

PURPOSE: Many patients with head-and-neck (H&N) cancer have tumor shrinkage and/or weight loss during the course of radiotherapy. We conducted this retrospective study to determine the dosimetric effects of repeat computed tomography (CT) imaging and replanning during the course of intensity-modulated radiotherapy (IMRT) on both normal tissues and target volumes. METHODS AND MATERIALS: A retrospective chart review identified 13 patients with H&N cancer treated with IMRT who had repeat CT imaging and replanning during the course of radiotherapy. The first IMRT plan for each patient was generated based on the original planning CT scan acquired before the start of treatment. Because of tumor shrinkage or weight loss during radiotherapy, a second CT scan was acquired, and a new plan was generated and used to complete the course of IMRT. CT-CT fusion was used to correct patient positioning differences between the scans. By using a commercial inverse IMRT planning system, a hybrid IMRT plan was generated for each patient by applying the beam configurations of the first IMRT plan (including the intensity profile of each beam) to the anatomy of the second CT scan. The dose-volume histograms of the actual and hybrid IMRT plans were compared using analysis of variance methods for repeated measures. RESULTS: All patients had locally advanced, nonmetastatic Stage III or IV disease, including 6 nasopharynx, 6 oropharynx, and 1 unknown primary site. All patients were treated with concurrent platinum-based chemotherapy. When replanning vs. not replanning was compared, the hybrid IMRT plans (without replanning) demonstrated reduced doses to target volumes and increased doses to critical structures. The doses to 95% (D95) of the planning target volumes of the gross tumor volume (PTVGTV) and the clinical target volume (PTVCTV) were reduced in 92% of patients, by 0.8-6.3 Gy (p=0.02) and 0.2-7.4 Gy (p=0.003), respectively. The maximum dose (Dmax) to the spinal cord increased in all patients (range, 0.2-15.4 Gy; p=0.003) and the brainstem Dmax increased in 85% of patients without replanning (range, 0.6-8.1 Gy; p=0.007). CONCLUSIONS: Repeat CT imaging and replanning during the course of IMRT for selected patients with H&N cancer is essential to identify dosimetric changes and to ensure adequate doses to target volumes and safe doses to normal tissues. Future prospective studies with larger sample sizes will help to determine criteria for repeat CT imaging and IMRT replanning for H&N cancer patients undergoing radiotherapy.

Adult↗

PubMed2005

A phase I trial of fixed dose rate gemcitabine and capecitabine in metastatic renal cell carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (RCC) has modest response rates to chemotherapy with gemcitabine and 5-fluorouracil (5-FU). Fixed dose rate gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. To determine the toxicity of this combination therapy in metastatic RCC, a Phase I trial was conducted. METHODS: Patients with metastatic RCC were enrolled in a Phase I dose escalation trial. Patients received fixed dose rate gemcitabine on Days 1, 8, and 15 in combination with capecitabine, an oral 5-FU analog, given on Days 1-21 of a 28-day cycle. RESULTS: Nine patients were enrolled at one of two dose levels. The initial dose level produced dose-limiting toxicity (DLT), including prominent palmar-plantar erythrodysesthesia (hand-foot syndrome). A modified second dose level also resulted in DLT, precluding further study. No central nervous system (CNS) toxicity was observed in three patients with CNS metastases. Two patients demonstrated an objective partial response. CONCLUSIONS: Fixed dose rate gemcitabine in combination with capecitabine produced unacceptable toxicity in patients with advanced RCC. Further development of this schedule in RCC cannot be recommended.

Adult↗

PubMed2005

A comparison of the phenotype and genotype in adenomatous polyposis patients with and without a family history.

OBJECTIVES: Adenomatous polyposis of the colon is often secondary to an inherited mutation in adenomatous polyposis coli (APC) gene, however, approximately one third of patients have no family history of the disease. We studied the phenotype and genotype of adenomatous polyposis in patients without a family history. METHODS: A cohort of 57 unrelated adenomatous polyposis patients were evaluated. Seventeen patients with no family history were compared with 40 patients who had a positive family history of the disease. Family history and medical records were collected and analyzed. Germline APC and Mut Y homologue (MYH) testing was undertaken. RESULTS: Patients without a family history were diagnosed with polyposis at an older age (41 years vs. 32 years) and presenting more frequently with symptoms (76 vs 20, P < 0.05). The number of colonic polyps and frequency of extracolonic manifestation associated with adenomatous polyposis did not differ between the two groups. APC mutations were detected less frequently among patients without a family history of the disease (4 out of 17 vs 25 out of 40, P=0.007), even among those with greater than 100 colorectal adenomas (4 out of 12 versus 21 out of 29, P=0.03). One homozygous MYH mutation carrier (G382D) was detected among the six patients without a family history and without a germline APC mutation who were tested. CONCLUSIONS: Adenomatous polyposis patients without a family history are usually diagnosed with symptoms, and at a later age. Phenotypically, they are similar to those with a family history. However, germline APC mutations are detected far less frequently in patients without a family history. A small percentage of these cases may be secondary to biallelic germline MYH mutations.

Adenomatous Polyposis Coli↗

PubMed2005

Combined modality treatment with high-dose-rate brachytherapy boost for locally advanced prostate cancer.

PURPOSE: This is a retrospective review of our experience using high-dose-rate (HDR) brachytherapy boost for prostate cancer. METHODS AND MATERIALS: During the study period, we recommended external beam radiotherapy (45 Gy) and HDR boost (18 Gy in three fractions) combined with hormonal therapy (HT) for 2 months before and during radiotherapy to patients with at least one of the following risk features: pretreatment prostate-specific antigen>10, Gleason score (GS)>or=7, and clinical T3 disease. Additional HT for 2 years after radiotherapy was recommended for patients with GS>7. To patients whose risk of positive nodes exceeded 15%, we recommended whole pelvic radiotherapy. We administered HDR via single implant, and all fractions were given within 24h. RESULTS: This report is based on our initial 64 patients treated with HDR boost. The median follow-up was 50 months (range 25-68 months). The 4-year estimates of overall and disease-free survival were 98% and 92%, respectively. One patient experienced late grade 4 gastrointestinal toxicity. CONCLUSIONS: HDR brachytherapy is an effective means of delivering conformal prostate radiotherapy, and may be used with whole pelvic radiotherapy and HT.

Aged↗

PubMed2005

The independent impact of extended pattern biopsy on prostate cancer stage migration.

PURPOSE: There are many factors impacting stage migration for prostate cancer. The number of prostate core biopsies is known to increase detection of prostate cancers. It is still unknown whether the number of biopsies is an independent predictor of tumor size. This is important as a number of studies show that tumor volume is an independent predictor of cancer progression. MATERIALS AND METHODS: Using the University of California, San Francisco Urologic Oncology database, a retrospective review of 378 patients undergoing radical prostatectomy by a single surgeon during 2000 to 2003 was performed. Patient and tumor specific variables including age, prostate specific antigen (PSA), number of biopsies, biopsy Gleason grade, tumor volume in the surgical specimen and surgical specimen tumor grade were studied. Univariate and multivariate statistical methods including multiple and logistic regression were used to characterize patients by the number of biopsy cores. Tests of significance to identify predictors of tumor size were based on the partial F statistic and the likelihood ratio test. RESULTS: A total of 317 eligible patients were studied, of whom 119 had 6 biopsies and 198 had more than 6 biopsies. The 2 groups of patients were evenly matched in terms of age, PSA and Gleason sum, with no statistically significant differences observed. On univariate analysis, mean tumor volume was larger for patients receiving 6 core biopsies vs greater than 6 core biopsies (3.85 vs 2.04 cc, p = 0.0009). Additionally, statistically significant differences were observed when comparing median tumor volumes, as well as excluding extremely large volume tumors. On multivariate analysis the number of biopsies performed (6 vs more than 6), was an independent predictor of tumor size (p = 0.006), controlling for primary Gleason score, Gleason sum, PSA as a continuous or categorical variable, year of biopsy and year of surgery. CONCLUSIONS: The use of extended pattern prostate biopsy templates results in the detection of smaller volume prostate cancers, independent of PSA and Gleason grade. These biopsy templates have contributed to the downward stage migration of prostate cancer detection and may possibly contribute to the risk of over detection.

Adult↗

PubMed2005

Adenoid cystic carcinoma of the major salivary glands treated with surgery and radiation.

OBJECTIVE: To examine patient characteristics, pathologic features, and treatment outcomes of adenoid cystic carcinoma of the major salivary glands. STUDY DESIGN: Retrospective review of patients in an academic medical center. METHOD: Review of medical records regarding demographics, extent of tumor, stage, histologic characteristics, and treatment outcomes of patients treated with surgery and postoperative radiation. RESULTS: Of the 33 patients, 19 (58%) were male, and 14 (42%) were female. The average age of presentation was 49 (range 22-81) years. Of the 29 patients fully staged at the time of diagnosis, 7 (24%) presented at American Joint Committee on Cancer stage I, 9 (31%) at stage II, 4 (14%) at stage III, and 9 (31%) at stage IV. The cribriform histologic subtype was predominant (64%). The majority originated in the parotid gland (21, 64%), with the remaining originating in either the submandibular gland (10, 30%) or the sublingual gland (2, 6%). Local control was 94% at 5 years and 73% at 10 years. Metastatic control was 82% at 5 years and 63% at 10 years. Four patients failed locally and nine failed distally. Overall survival was 85% at 5 years and 69% at 10 years, with a median of 12.9 years. CONCLUSION: Surgical excision with postoperative radiation provides a long period of disease-free survival. Patients were more likely to fail with metastases than with local recurrence.

Adult↗

PubMed2005

Antigen-presenting cells 8015 (Provenge) in patients with androgen-dependent, biochemically relapsed prostate cancer.

BACKGROUND: Antigen-presenting cells 8015 (APC8015; Provenge) is an immunotherapeutic product designed to initiate a T-cell-mediated immune response against prostatic acid phosphatase, an antigen overexpressed in 95% of prostate cancer cells. In phase I/II trials, APC8015 has shown immunologic and clinical responses in patients with androgen-independent prostate cancer. This phase II trial was conducted to assess the prostate-specific antigen (PSA)-modulating effects of APC8015 in patients with androgen-dependent prostate cancer (ADPC) with biochemical progression. PATIENTS AND METHODS: Patients with nonmetastatic recurrent disease as manifested by increasing PSA levels (0.4-6.0 ng/mL) and who had undergone previous definitive surgical or radiation therapy were enrolled. Therapy consisted of APC8015 infusion on weeks 0, 2, and 4 (ie, 3 infusions). Prostate-specific antigen was measured at baseline and monthly until disease progression, defined as a doubling of the baseline or nadir PSA value (whichever was lower) to > or = 4 ng/mL or development of distant metastases. RESULTS: Thirteen of 18 patients demonstrated an increase in PSA doubling time (PSADT), with a median increase of 62% (4.9 months before treatment vs. 7.9 months after treatment; P = 0.09; signed-rank test). CONCLUSION: Therapy was well tolerated. APC8015 as single-agent immunotherapy for patients with ADPC and biochemical progression did not result in > or = 50% decrease in PSA from baseline levels but did appear to modulate PSADT in some patients. Further manipulations of host immunity may be required to achieve a significant antitumor effect.

Adenocarcinoma↗