Richard Sorace

We have treated 76 patients with locally advanced breast cancer, 31 with stage IIIA, 41 with stage IIIB, and 4 with stage IV disease, with primary induction chemotherapy including an attempted hormonal synchronization in 70 patients. All were treated to maximum objective clinical response before proceeding to any local therapy. Patients achieving a complete response with a negative repeat biopsy generally received radiation therapy while patients with residual disease, partial response (PR) or no change (NC) status received debulking surgery prior to radiation therapy. Regardless of response to induction chemotherapy, patients received at least 6 additional months of chemotherapy following local therapy. Initial doses of combination chemotherapy were escalated to targeted myelosuppression. The objective response rate to induction chemotherapy was 93% with 49% complete response (CR), 44% PR, and 7% NC. The median numbers of cycles of chemotherapy to achieve a CR, PR, or NC were 5, 3, and 5, respectively. Three patients who currently have PRs are still on chemotherapy with continued tumor regression. Of 37 patients achieving a CR to chemotherapy, 35 were assessed by biopsies to determine pathological evidence of response. Twenty-three of the 37 patients (62%) were proven to be complete responders with negative biopsies. Twenty-four patients have relapsed, 6 with stage IIIA, 16 with stage IIIB, and 2 with stage IV. Five patients have had locoregional relapses alone, 4 locoregional and distant, and 15 distant alone. Median time to progression is 35.9 months for stage IIIA and 34.2 months for stage IIIB. Median survival is 35.3 months for stage IIIB and is indeterminate for stage IIIA. This aggressive primary chemotherapy regimen with hormonal synchronization followed by local therapy appears to provide excellent local control and encouraging early results on systemic disease control.

BACKGROUND: This study summarizes long-term outcomes from treatment of prostate cancer with increased risk of extracapsular cancer extension (ECE) using brachytherapy-based treatment. METHODS: A total of 282 consecutive patients were treated from 1992-1996 by 1 author (M.D.). Two hundred forty-three patients had at least 1 higher risk feature for ECE including Gleason Score 7-10 (172), prostate-specific antigen (PSA) above 10 (166), and clinical stages T(2c) (109) and T(3) (107). Using National Comprehensive Cancer Network (NCCN) guidelines, 119 patients had intermediate-risk disease and 124 had high-risk disease. Patients received pelvic 3-dimensional conformal external beam radiation followed by a palladium (Pd)-103 boost. Generous brachytherapy margins were utilized. Biochemical failure was defined using ASTRO Consensus Definition, nadir +2 and PSA >0.2 ng/mL at last follow-up. The nonfailing patient follow-up period was 1-14 years (median, 9.5 years). Biochemical data and original biopsy slides were independently re-reviewed at the University of Washington (by K.W. and L.T., respectively). RESULTS: Overall actuarial freedom from biochemical progression at 14 years was 81%, including 87% and 72% having intermediate and high-risk disease, respectively. Absolute risk of failure decreased progressively, falling to 1% beyond 6 years after treatment. All failing patients had prostate biopsies without evidence of local recurrence. The strongest predictor of failure was Gleason score (P = .03) followed by PSA (P = .041). Treatment morbidity was limited to temporary RTOG grade 1-2 urinary and gastrointestinal symptoms. CONCLUSIONS: High tumor control rates are possible with beam radiation followed by Pd-103 brachytherapy. Despite perceptions that brachytherapy is inappropriate for patients at higher risk for ECE, this series strengthens the rationale that brachytherapy-based treatment may be a desirable modality for such patients.

Abstract BACKGROUND The objective of this study was to define the long‐term prognostic significance of prostatic acid phosphatase (PAP) levels in patients with higher risk, early‐stage prostate carcinoma. METHODS One hundred sixty‐one consecutive patients with Stage T1–T3 prostate carcinoma (according to the 1992 criteria of the American Joint Committee on Cancer) were treated from 1992 through 1996. Each patient had a Gleason score ≥ 7 and/or a prostate specific antigen (PSA) level > 10 ng/mL. The original biopsy slides for 130 of 161 patients were retrieved and rereviewed by a single pathologist (L.T.). Enzymatic PAP measurements were determined using a standard method. Values up to 2.5 Units were considered normal. Patients received 41 grays (Gy) of external beam radiation therapy to a limited pelvic field followed 4 weeks later by a palladium 103 (Pd‐103) boost using transrectal ultrasound and fluoroscopic guidance as described previously. The prescribed minimum Pd‐103 dose to the prostate was 80 Gy (pre‐National Institute of Standards and Technology [NIST]‐99). Freedom from biochemical failure was defined as a serum PSA level ≤0.2 ng/mL at last follow‐up. RESULTS There was little correlation between pretreatment PSA levels, Gleason scores, and PAP measurements. Thirty‐eight patients developed biochemical failure. The overall actuarial freedom from biochemical progression at 10 years is 79%, with 118 patients followed for > 5 years. In a multivariate Cox proportional hazards analysis that considered each factor as a continuous variable, the strongest predictor of failure was PAP ( P = 0.0001), followed by Gleason score ( P = 0.13 ), and PSA ( P = 0.04). PAP was especially helpful in stratifying patients with pretreatment PSA levels between 4 ng/mL and 20 ng/mL, for whom the prognosis does not different when they are subdivided into PSA categories. When the PAP subgroup analysis was limited to this relatively favorable group, there was a wide range of prognoses. CONCLUSIONS The biochemical cure rate was remarkably high among the 161 patients evaluated. The fact that the PAP was the strongest predictor of long‐term biochemical failure in patients with otherwise higher risk features reported here suggests that it may be a more accurate indicator of micrometastatic disease compared with the Gleason score and the PSA level. This report adds to the rationale for reintroducing PAP measurement into general practice. Cancer 2003;97:979–83. © 2003 American Cancer Society. DOI 10.1002/cncr.11154