Daphna Y. Spiegel

Randomized Trial Comparing Conventional-Dose With High-Dose Conformal Radiation Therapy in Early-Stage Adenocarcinoma of the Prostate: Long-Term Results From Proton Radiation Oncology Group/American College of Radiology 95-09

PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes. PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen </= 15 ng/mL were randomly assigned to a total dose of either 70.2 Gray equivalents (GyE; conventional) or 79.2 GyE (high). No patient received androgen suppression therapy with radiation. Local failure (LF), biochemical failure (BF), and overall survival (OS) were outcomes. Results A total of 393 men were randomly assigned, and median follow-up was 8.9 years. Men receiving high-dose radiation therapy were significantly less likely to have LF, with a hazard ratio of 0.57. The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4% for conventional-dose and 16.7% for high-dose radiation therapy (P < .0001). This difference held when only those with low-risk disease (n = 227; 58% of total) were examined: 28.2% for conventional and 7.1% for high dose (P < .0001). There was a strong trend in the same direction for the intermediate-risk patients (n = 144; 37% of total; 42.1% v 30.4%, P = .06). Eleven percent of patients subsequently required androgen deprivation for recurrence after conventional dose compared with 6% after high dose (P = .047). There remains no difference in OS rates between the treatment arms (78.4% v 83.4%; P = .41). Two percent of patients in both arms experienced late grade >/= 3 genitourinary toxicity, and 1% of patients in the high-dose arm experienced late grade >/= 3 GI toxicity. CONCLUSION This randomized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation. This was achieved without an increase in grade >/= 3 late urinary or rectal morbidity.

Long-Term Outcomes of Selective Bladder Preservation by Combined-Modality Therapy for Invasive Bladder Cancer: The MGH Experience

BACKGROUND Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown. OBJECTIVE Report long-term outcomes of patients with muscle-invasive BCa treated by CMT. DESIGN, SETTING, AND PARTICIPANTS We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2-4a disease between 1986 and 2006. Median follow-up for surviving patients was 7.7 yr. INTERVENTIONS Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy (RT) after maximal transurethral resection of bladder tumor (TURBT) plus neoadjuvant or adjuvant chemotherapy. Repeat biopsy was performed after 40 Gy, with initial tumor response guiding subsequent therapy. Those patients showing complete response (CR) received boost chemotherapy and RT. One hundred two patients (29%) underwent RC-60 for less than CR and 42 for recurrent invasive tumors. MEASUREMENTS Disease-specific survival (DSS) and overall survival (OS) were evaluated using the Kaplan-Meier method. RESULTS AND LIMITATIONS Seventy-two percent of patients (78% with stage T2) had CR to induction therapy. Five-, 10-, and 15-yr DSS rates were 64%, 59%, and 57% (T2=74%, 67%, and 63%; T3-4=53%, 49%, and 49%), respectively. Five-, 10-, and 15-yr OS rates were 52%, 35%, and 22% (T2: 61%, 43%, and 28%; T3-4=41%, 27%, and 16%), respectively. Among patients showing CR, 10-yr rates of noninvasive, invasive, pelvic, and distant recurrences were 29%, 16%, 11%, and 32%, respectively. Among patients undergoing visibly complete TURBT, only 22% required cystectomy (vs 42% with incomplete TURBT; log-rank p<0.001). In multivariate analyses, clinical T-stage and CR were significantly associated with improved DSS and OS. Use of neoadjuvant chemotherapy did not improve outcomes. No patient required cystectomy for treatment-related toxicity. CONCLUSIONS CMT achieves a CR and preserves the native bladder in >70% of patients while offering long-term survival rates comparable to contemporary cystectomy series. These results support modern bladder-sparing therapy as a proven alternative for selected patients.

Outcomes of proton therapy for patients with functional pituitary adenomas.

PURPOSE/OBJECTIVE(S) This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). METHODS AND MATERIALS We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥ 3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported. RESULTS With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone-secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors. CONCLUSIONS Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary adverse effect.

Prostatic Duct Adenocarcinoma: Clinical Characteristics, Treatment Options, and Outcomes – a Rare Cancer Network Study

Background: To evaluate the clinical characteristics, contemporary treatment options, and outcome of prostatic duct adenocarcinoma (PDA), we initiated a Rare Cancer Network (RCN) study. Materials and Methods: Six member institutions of the RCN collected clinical data on 31 patients. Treatment consisted of definitive radiotherapy in 14 patients and radical prostatectomy in 16 patients. One patient was treated with androgen deprivation alone. The mean follow-up period was 56 months. Results: Of the 14 patients managed with radiotherapy, 1 patient developed bone metastases and died of prostate cancer, and 1 patient had a biochemical relapse 8 years after definitive radiotherapy. Of the 16 patients who underwent radical prostatectomy, 2 patients developed bone metastases, one of who died of disease. Three patients that relapsed after prostatectomy were successfully salvaged with radiotherapy. The patient that was treated with androgen deprivation alone developed bone metastases at 10 months, was treated with chemotherapy, and was alive after 22 months. Conclusions: Our results suggest that PDA is a cancer with a behavior similar to that of high Gleason grade acinar carcinoma. Good local control can be achieved by either radiation or surgery. Postoperative radiotherapy seems to work as an adjuvant or salvage treatment, and most tumors appear to respond to androgen deprivation.

Breast Cancer: Biology or Stage?

A 44-year-old woman was found to have 2 groups of calcifications within the left breast on routine screening mammogram: one at 2 o’clock measuring 28 mm and a second at 3 o’clock measuring 40 mm. Follow-up diagnostic mammogram confirmed multiple groups of pleomorphic calcifications spanning >7 cm in the upper outer quadrant. Stereotactic core needle biopsy noted invasive carcinoma, predominantly lobular type, grade 2, estrogen receptor positive (Allred 8), progesterone receptor positive (Allred 8), HER2 negative (0) at the 2 o’clock site; and ductal carcinoma in situ without invasion at 3 o’clock. Mastectomy with sentinel lymph node biopsy revealed 2 sites of invasive disease. The first was a