The use of Hormonal Therapy to Augment Radiation Therapy in Prostate Cancer: An Update.

PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) is an important adjunctive therapy to external beam radiation therapy (RT) for the definitive management of prostate cancer. The role of ADT is well-established for locally advanced or high-risk disease in conjunction with standard doses of RT, but less defined for intermediate-risk disease or with dose-escalated RT. The goal of this review is to summarize evidence evaluating the combination of ADT/RT, focusing on recent trials and current controversies as they pertain to the practicing clinician. RECENT FINDINGS: The benefit of ADT on biochemical control is maintained with dose-escalated RT according to recently reported phase III studies. Furthermore, there is now prospective, randomized evidence to support the addition of ADT to RT in the post-prostatectomy setting. ADT continues to play an important role for prostate cancer patients receiving dose-escalated RT. Future research is needed to identify subgroups most likely to benefit from this combination.

IBCD: development and testing of a checklist to improve quality of care for hospitalized general medical patients.

BACKGROUND: Several studies have demonstrated the usefulness of medical checklists to improve quality of care in surgery and the ICU. The feasibility, effectiveness, and sustainability of a checklist was explored. METHODS: Literature on checklists and adherence to quality indicators in general medicine was reviewed to develop evidence-based measures for the IBCD checklist: (I) pneumococcal immunization, (B) pressure ulcers (bedsores), (C) catheter-associated urinary tract infections (CAUTIs), and (D) deep venous thrombosis (DVT) were considered conditions highly relevant to the quality of care in general medicine inpatients. The checklist was used by attending physicians during rounds to remind residents to perform four actions related to these measures. Charts were audited to document actions prompted by the checklist. RESULTS: The IBCD checklist was associated with significantly increased documentation of and adherence to care processes associated with these four quality indicators. Seventy percent (46/66) of general medicine teams during the intervention period of July 2010-March 2011 voluntarily used the IBCD checklist for 1,168 (54%) of 2,161 patients. During the intervention period, average adherence for all four checklist items increased from 68% on admission to 82% after checklist use (p < .001). Average adherence after checklist use was also higher when compared to a historical control group from one year before implementation (82% versus 50%, p < .0001). In the six weeks after the checklist was transitioned to the electronic medical record, IBCD was noted in documentation of 133 (59%) of 226 patients admitted to general medicine. CONCLUSION: A checklist is a useful and sustainable tool to improve adherence to, and documentation of, care processes specific to quality indicators in general medicine.

PI-RADS score is associated with biochemical control and distant metastasis in men with intermediate-risk and high-risk prostate cancer treated with radiation therapy.

BACKGROUND: Novel methods of risk stratification are needed for men with prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) uses multiparametric MRI (mpMRI) to assign a score indicating the likelihood of clinically significant prostate cancer. We evaluated pretreatment mpMRI findings, including PI-RADS score, as a marker for outcome in patients treated with primary radiation therapy (RT). METHODS: One hundred and twenty-three men, 64% and 36% of whom had National Comprehensive Cancer Network (NCCN) intermediate-risk and high-risk disease, respectively, underwent mpMRI prior to RT. PI-RADS score and size of the largest nodule were analyzed with respect to freedom from biochemical failure (FFBF) and freedom from distant metastasis. RESULTS: A PI-RADS score of ≤3, 4, or 5 was defined in 7%, 49%, and 44%; with a median nodule size of 0, 8, and 18 mm, respectively (P < 0.001). Median follow-up was 67 months. Men with PI-RADS ≤ 3, 4, or 5 disease had 7-year FFBF of 100%, 92%, and 65% (P = 0.002), and a 7-year freedom from distant metastasis of 100%, 100%, and 82%, respectively (P = 0.014). PI-RADS (Hazard Ratio 5.4 for PI-RADS 5 vs. 4, P = 0.006) remained associated with FFBF when controlling for NCCN risk category (P = 0.063) and receipt of androgen deprivation therapy (P = 0.535). Nodule size was also associated with FFBF (Hazard Ratio 1.08 per mm, P < 0.001) after controlling for NCCN risk category (P = 0.156) and receipt of androgen deprivation therapy (P = 0.776). CONCLUSION: mpMRI findings, including PI-RADS score and nodule size, may improve risk stratification in men treated with primary RT.

Pretreatment multiparametric MRI is independently associated with biochemical outcome in men treated with radiation therapy for prostate cancer.

PURPOSE: The purpose of this study was to investigate the utility of pre-treatment multiparametric magnetic resonance imaging (mpMRI) in a modern cohort of intermediate and high-risk prostate cancer patients treated with primary radiotherapy. METHODS AND MATERIALS: One hundred twenty three men with National Comprehensive Cancer Network (NCCN) intermediate or high-risk prostate cancer were treated with primary EBRT and/or brachytherapy and had evaluable pre-treatment mpMRI with endorectal coil. Images were assessed for the presence of radiographic extraprostatic extension (rEPE), seminal vesicle invasion (rSVI), lymph node involvement (LNI), sextant involvement, and largest axial tumor diameter. Imaging characteristics were analyzed along with clinical risk factors against freedom from biochemical failure (FFBF). Median follow-up time was 50 months. RESULTS: Fourteen (11%) men developed biochemical failure. The 5-year FFBF was 94% in intermediate-risk patients and 82% in high-risk patients (p < 0.01). mpMRI findings including rEPE (29% vs. 66%, p < 0.01), rSVI (6% vs. 25%, p < 0.01), LNI (1% vs. 30%, p < 0.01), and largest axial tumor size> 15 mm (27% vs. 48%, p = 0.02) were identified in men with intermediate vs. high risk prostate cancer, respectively. mpMRI features associated with 5-y FFBF biochemical failure on univariate analysis included rEPE (80% vs 98%), rSVI (55% vs. 96%), LNI (65% vs. 93%), and largest axial tumor size >15mm (81% vs. 94%, all p < 0.01). Men without any high risk MRI finding had a 5-y FFBF of 100% vs. 81% (p < 0.01). Adverse imaging features (HR 8.9, p < 0.01) were independently associated with biochemical failure in a bivariate model analyzed alongside clinical risk category (HR 3.2, p = 0.04). CONCLUSIONS: Pre-treatment mpMRI findings are strongly associated with biochemical outcomes in a modern cohort of intermediate and high-risk patients treated with primary radiotherapy. mpMRI may aid risk stratification beyond clinical risk factors in men treated with radiation therapy; further study is warranted to better understand how mpMRI can be used to individualize therapy.

Triple-tandem high-dose-rate brachytherapy for early-stage medically inoperable endometrial cancer: Initial report on acute toxicity and dosimetric comparison to stereotactic body radiation therapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) may be appealing in medically inoperable endometrial cancer to avoid procedural risks. We performed a dosimetric comparison to triple-tandem, high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: Six consecutive clinical stage I, grade 1-2, medically inoperable endometrial cancer patients were treated with triple-tandem HDR brachytherapy. We report patient factors and acute toxicity. Also, we performed dosimetric comparison to SBRT using both 3D conformal arc (3DArc) and volumetric-modulated arc therapy. D2cc values for normal tissues were calculated and compared to the HDR plans. RESULTS: Median age was 57 years. Patient comorbidities included morbid obesity, congestive heart failure, diabetes, and pulmonary emboli. In three patients who received prior external beam radiation (EBRT), median EBRT and HDR doses were 46 Gy and 20 Gy, respectively. The median dose with HDR brachytherapy monotherapy was 35 Gy. Acute toxicities during EBRT included gastrointestinal (3/3 with grade 1-2) and genitourinary (3/3 with grade 1-2). Acute toxicities during HDR brachytherapy were gastrointestinal (2/6 total with grade 1-2) and genitourinary (2/6 total with grade 1). The mean D2cc/Gy of prescription dose for rectum, sigmoid, and bladder were 0.58, 0.40, and 0.47 respectively. Overall, doses to normal tissues were higher for SBRT plans as compared to HDR. Also, the R50 (ratio of the 50% prescription isodose volume to the PTV) was lowest with HDR brachytherapy. CONCLUSIONS: In medically inoperable, clinical stage I endometrial cancer patients with multiple comorbidities, definitive triple-tandem, HDR brachytherapy results in mild acute toxicity. In addition, HDR brachytherapy achieves relatively lower doses to surrounding normal tissues as compared to SBRT.

Case Report of Bone Marrow-Sparing Proton Therapy Craniospinal Irradiation for Central Nervous System Myelomatosis.

Central nervous system (CNS) involvement is rare but it is an increasingly recognized complication of the multiple myeloma. The craniospinal radiotherapy is a standard treatment option, however, it may be challenging to deliver due to hematologic toxicity in the patients with multiple prior systemic therapies. We report a case of CNS myelomatosis in a patient with prior stem cell transplant multiple systemic therapies treated with bone marrow-sparing proton therapy craniospinal irradiation, with the dramatic clinical response and minimal hematologic toxicity.