A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer.

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.

PErspective and current status of Radiotherapy Service in IRan (PERSIR)-1 study: assessment of current external beam radiotherapy facilities, staff and techniques compared to the international guidelines.

BACKGROUND AND PURPOSE: Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. MATERIALS AND METHODS: A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. RESULTS: Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. CONCLUSION: There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.

Pathologic primary tumor factors associated with risk of lymph node involvement in patients with non-endometrioid endometrial cancer.

PURPOSE/OBJECTIVES: Lymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly well-established for endometrial adenocarcinoma, but it is not as well defined whether these factors similarly predict LN positivity in less common histologies. MATERIALS/METHODS: Patients diagnosed with pathologic T1-T2 carcinosarcoma, clear cell, uterine papillary serous carcinoma (UPSC), and mixed histologic type endometrial cancer between 2004 and 2016 undergoing primary surgery with at least 1 lymph node sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Nomograms were created to predict overall, pelvic only, and paraaortic with or without pelvic LN involvement. RESULTS: Among 11,390 patients included, 1950 (18%) were node positive. On multivariable analysis, increasing pathologic tumor stage (pT2 versus pT1a, odds ratio [OR] 3.63, 95% confidence interval [CI] 3.15-4.18, p < 0.001), increase in tumor size per centimeter (OR 1.08, 95% CI 1.06-1.10, p < 0.001), and the presence of lymphovascular invasion (LVI) (OR 4.97, 95% CI 4.43-5.57, p < 0.001) were predictive of overall LN positivity. Relative to carcinosarcoma, both clear cell (OR 1.54, 95% CI 1.22-1.95, p < 0.001) and UPSC (OR 1.73, 95% CI 1.48-2.02, p < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.07, 95% CI 0.92-1.24, p = 0.42). CONCLUSION: Among patients with non-endometrioid endometrial cancer, predictors of LN positivity are similar to endometrial adenocarcinoma. The nomograms provided could be helpful in making adjuvant treatment decisions for these less common histologies.

Evaluation of patterns of progression on poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance in ovarian cancer: a cross-sectional study.

INTRODUCTION: Despite improvement in progression-free survival with poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy for ovarian cancer, many patients will eventually progress on therapy. Oligoprogression is uniquely suited to considerations of local consolidation therapy in this setting, but not commonly used in ovarian cancer. In this study we evaluated the proportion of patients on PARPi maintenance who developed limited sites of disease, the location of progression, and their natural history. METHODS: From January 2006 to December 2020, natural language processing software (DEEP6AI) was used to identify 58 patients with ovarian cancer treated with PARPi maintenance after complete or partial response after surgery and platinum-based chemotherapy at our institution. Patients were assessed for presence and location of recurrence based on radiologic findings. RESULTS: The median patient age was 65 (IQR 57-71) years. Patients had a median of two lines of chemotherapy prior to starting PARPi. With a median follow-up of 48 (range 12-149) months, 32 (55%) patients had a recurrence on maintenance olaparib and 11 (34%) patients developed oligoprogression (≤3 sites). For the 11 patients with oligoprogression, three patients developed recurrence in one site, five in two sites, and three in three sites. The sites of oligoprogression were pelvic/periaortic nodal (27%), peritoneal (27%), liver (27%), lung/mediastinal (14%), and brain (5%). The median progression-free survival for the entire cohort was 6.0 months (95% CI 4.2 to 7.8); median overall survival was not met. There were no significant differences in overall survival (p=0.81) or progression-free survival (p=0.95) between patients with and without oligoprogression. CONCLUSIONS: One-third of patients on PARPi maintenance experienced oligoprogression defined as limited to ≤3 sites. These patients may benefit from local consolidation therapy. A larger dataset is needed to validate these findings to assess if trials investigating local therapy for these patients is of value.

Integrating PARP Inhibitors Into Advanced Prostate Cancer Therapeutics.

DNA-damage repair (DDR) pathway mutations can sensitize cancer cells to a class of cancer therapeutics known as PARP inhibitors. Given that DDR alterations can be found in up to one-third of advanced prostate cancers, PARP inhibitors have recently been established in treatment-refractory settings. We provide an updated review of the clinical data supporting the 4 PARP inhibitors that have undergone the most investigation thus far in metastatic castrate-resistant prostate cancer (mCRPC). Two of these agents are currently approved for the treatment of DDR-altered mCRPC. We end with a discussion on integration of approved PARP inhibitors into advanced prostate cancer clinical practice.

A proposal for a new classification of "unfavorable risk criteria" in patients with stage I endometrial cancer.

BACKGROUND: Randomized trials describe differing sets of high-intermediate risk criteria. OBJECTIVE: To use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different criteria, and define a classification of "unfavorable risk." METHODS: Patients with stage I endometrial cancer between January 2010 and December 2014 were identified in the National Cancer Database and stratified into two cohorts: (1) patients meeting Gynecologic Oncology Group (GOG)-99 criteria only for high-intermediate risk, but not Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 criteria and (2) those meeting PORTEC-1 criteria only. High-risk stage I patients with both FIGO stage IB (under FIGO 2009 staging) and grade 3 disease were excluded. In each cohort, propensity score-matched survival analyses were performed. Based on these analyses, we propose a new classification of unfavorable risk. We then analyzed the association of adjuvant radiation with survival, stratified by this classification. RESULTS: We identified 117,272 patients with stage I endometrial cancer. Of these, 11,207 patients met GOG-99 criteria only and 5,920 patients met PORTEC-1 criteria only. After propensity score matching, adjuvant radiation therapy improved survival (HR=0.73; 95% CI 0.60 to 0.89; p=0.002) in the GOG-99 only cohort. However, there was no benefit of adjuvant radiation (HR=0.89; 95% CI 0.69 to 1.14; p=0.355) in the PORTEC-1 only cohort. We, therefore, defined unfavorable risk stage I endometrial cancer as two or more of the following risk factors: lymphovascular invasion, age ≥70, grade 2-3 disease, and FIGO stage IB. Adjuvant radiation improved survival in stage I patients with adverse risk factors (HR=0.74; 95% CI 0.68 to 0.80; p<0.001), but not in other stage I patients (HR=1.02; 95% CI 0.91 to 1.15; p=0.710; p interaction <0.001). CONCLUSION: Our study showed that adjuvant radiation was associated with an overall survival benefit in patients meeting GOG-99 criteria only; however, no survival benefit was seen in patients meeting PORTEC-1 criteria only. We propose a definition of unfavorable risk stage I endometrial cancer: ≥2 risk factors from among lymphovascular invasion, age ≥70, grade 2-3 disease, and FIGO stage IB disease.

Underutilization of brachytherapy and disparities in survival for patients with cervical cancer in California.

PURPOSE: The treatment for locally advanced cervical cancer is external beam radiation (EBRT), concurrent chemotherapy, and brachytherapy (BT). We investigated demographic and socioeconomic factors that influence trends in BT utilization and disparities in survival. METHODS: Using the California Cancer Registry, cervical cancer patients FIGO IB2-IVA from 2004 to 2014 were identified. We collected tumor, demographic and socioeconomic (SES) factors. We used multivariable logistic regression analysis to determine predictors of use of BT. Using Cox proportional hazards, we examined the impact of BT vs EBRT boost on cause specific (CSS) and overall survival (OS). RESULTS: We identified 4783 patients with FIGO stage 11% IB2; 32% II, 54% III, 3% IVA. Nearly half (45%) of patients were treated with BT, 18% were treated with a EBRT boost, and 37% had no boost. Stage II and III were more likely to be treated with BT (p = 0.002 and p = 0.0168) vs Stage IB2. As patients aged, the use of BT decreased. Using multivariate analysis, BT impacted CCS (HR 1.16, p = 0.0330) and OS (HR 1.14, p = 0.0333). Worse CSS was observed for black patients (p = 0.0002), low SES (p = 0.0263), stage III and IVA (p < 0.0001. Black patients, low and middle SES had worse OS, (p = 0.0003). CONCLUSIONS: The utilization of BT in locally advanced cervical cancer was low at 45%, with a decrease in CSS and OS. Black patients and those in low SES had worse CSS. As we strive for outcome improvement in cervical cancer, we need to target increasing access and disparities for quality and value.

NEW ULTRA-WIDE-FIELD ANGIOGRAPHIC GRADING SCHEME FOR RADIATION RETINOPATHY AFTER IODINE-125 BRACHYTHERAPY FOR UVEAL MELANOMA.

PURPOSE: Radiation retinopathy remains incompletely characterized and may cause severe vision loss. Ultra-wide-field fluorescein angiography provides a pan-fundus view of vascular alterations caused by radiation treatment and may predict visual and ocular outcomes. We have developed a grading scheme to describe pan-fundus severity and to predict the progression of radiation retinopathy in patients treated for uveal melanoma with iodine-125 brachytherapy. METHODS: A retrospective review of patients treated with standard iodine-125 brachytherapy for uveal melanoma at the Ophthalmic Oncology Center at the University of California, Los Angeles, who had undergone both baseline and postbrachytherapy ultra-wide-field fluorescein angiography. A grading scheme was devised based on observations of vascular leakage, retinal perfusion status, and retinal proliferation. The correlation of grade severity with patient characteristics, tumor features, visual acuity, optical coherence tomography findings, and neovascular glaucoma was measured with chi-square and one-way analysis of variance analyses. RESULTS: Sixty-seven patients were identified for review. Consistent wide-field angiographic patterns after brachytherapy were observed and graded as follows: Grade 0: normal; Grade 1: late foveal leakage; Grade 2: late peripheral leakage; Grade 3: presence of nonperfusion; and Grade 4: retinal neovascularization. Six eyes (8.9%) were Grade 0; 16 (23.8%) were Grade 1; 25 (37.3%) were Grade 2; 16 (23.4%) were Grade 3; and 4 (6.0%) were Grade 4. Higher grade radiation severity correlated significantly with duration of follow-up (P < 0.02); younger age (P = 0.035); worse visual acuity (P = 0.001); cystoid macular edema or atrophy on optical coherence tomography (P < 0.0001); and neovascular glaucoma (P = 0.003). CONCLUSION: Wide-field fluorescein angiography revealed distinct fundus-wide patterns of vascular damage, which were progressive in nature in eyes treated with iodine-125 brachytherapy for uveal melanoma and correlated with signs of progressive vascular injury. This grading scheme may have prognostic value to predict the progression of radiation retinopathy and to prognosticate visual outcomes in patients undergoing brachytherapy.

Clinical Outcomes for Stereotactic Ablative Radiotherapy in Oligometastatic and Oligoprogressive Gynecological Malignancies.

OBJECTIVES: We report single-institution clinical outcomes of women treated with stereotactic ablative radiotherapy (SABR) for oligometastatic or progressive gynecological malignancies. MATERIALS AND METHODS: From 2009 to 2015, 47 lesions from 28 patients were treated with SABR and retrospectively analyzed. All patients had oligometastatic (93%) or oligoprogressive (7%) disease. Primary cancer diagnoses were 15 ovarian, 8 endometrial, 2 cervical, 2 vaginal, and 1 uterine carcinosarcoma. Treatment was delivered using a median of 5 fractions to a median total dose of 40 Gy. Targets were grouped by treatment site and assessed for response using Response Evaluation Criteria in Solid Tumors v1.1. Mean biologically effective dose and pre-SABR tumor size were compared with response. Progression-free survival (PFS) was determined using Kaplan-Meier analysis, and toxicity outcomes were graded using Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Median follow-up was 12.8 months. Target locations were 17% liver, 21% lung, 17% paraaortic node, 26% other node, and 19% pelvic soft tissue. After treatment, 34% of targets were stable (SD), 32% had a partial response (PR), 17% had a complete response (CR), and 17% had progressive disease (PD). No failures occurred in lung or nodal targets. Mean ± standard deviation pre-SABR tumor diameter was 24 ± 22 mm. There was a significant difference in mean size between lesions that had a favorable (SD, PR, and CR) versus unfavorable response (PD) (17.2 vs 57.6 mm, P = 0.0044). Lesions that responded favorably were also more likely to have received a higher biologically effective dose (79.0 vs 59.6 Gy, P = 0.027). Median PFS was 10.8 months, and 1 patient experienced grade 3 toxicity. CONCLUSIONS: The SABR is a safe and effective local treatment modality in patients with oligometastatic gynecological disease. Distant progression remains the primary mode of failure in this patient population. In carefully selected patients, a combination of systemic treatment and SABR may offer long-term PFS.

Juxtapapillary and circumpapillary choroidal melanoma: globe-sparing treatment outcomes with iodine-125 notched plaque brachytherapy.

PURPOSE: Managing juxtapapillary and circumpapillary choroidal melanoma with brachytherapy is challenging because of technical complications with accurate plaque placement and high radiation toxicity given tumor proximity to the optic nerve. We evaluated our center's experience using ultrasound-guided, Iodine (I)-125 notched plaque brachytherapy for treating choroidal melanoma contiguous with (juxtapapillary) and at least partially surrounding the optic disc (circumpapillary). METHODS: All cases of choroidal melanoma treated with I-125 notched plaque brachytherapy at our center from September 2003-December 2013 were retrospectively reviewed. Only patients with ≥18 months of follow-up who had lesions contiguous with the optic disc (0 mm of separation) were included. The tumor apex prescription dose was 85 Gy. Outcomes evaluated included local control, distant metastasis-free survival (DMFS), cancer-specific survival (CSS), overall survival (OS), visual acuity, and radiation toxicity. RESULTS: Thirty-four patients were included with a median follow-up of 44.1 months (range 18.2-129.0). AJCC T-category was T1 in 58.8%, T2 in 26.5%, and T3 in 14.7%. Median circumferential optic disc involvement was 50% (range 10%-100%). Eye retention was achieved in 94.1%. Actuarial 2- and 4-year rates of local recurrence were 3.1% and 7.6%, DMFS were 97.0% and 88.5%, CSS were 97.0% and 92.8%, and OS were 97.0% and 88.9%, respectively. In addition, 23.5% had visual acuity ≥20/200 at last follow-up. CONCLUSIONS: I-125 notched plaque brachytherapy provides high eye preservation rates with acceptable longer-term post-treatment visual outcomes. Based on our experience, choroidal melanoma directly contiguous with and partially encasing the optic disc may be effectively treated with this technique.

Utilizing time-driven activity-based costing to understand the short- and long-term costs of treating localized, low-risk prostate cancer.

BACKGROUND: Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time-driven activity-based costing (TDABC) for competing treatments of low-risk prostate cancer. METHODS: Process maps were developed for each phase of care from the initial urologic visit through 12 years of follow-up for robotic-assisted laparoscopic prostatectomy (RALP), cryotherapy, high-dose rate (HDR) and low-dose rate (LDR) brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and active surveillance (AS). The last modality incorporated both traditional transrectal ultrasound (TRUS) biopsy and multiparametric-MRI/TRUS fusion biopsy. The costs of materials, equipment, personnel, and space were calculated per unit of time and based on the relative proportion of capacity used. TDABC for each treatment was defined as the sum of its resources. RESULTS: Substantial cost variation was observed at 5 years, with costs ranging from $7,298 for AS to $23,565 for IMRT, and they remained consistent through 12 years of follow-up. LDR brachytherapy ($8,978) was notably cheaper than HDR brachytherapy ($11,448), and SBRT ($11,665) was notably cheaper than IMRT, with the cost savings attributable to shorter procedure times and fewer visits required for treatment. Both equipment costs and an inpatient stay ($2,306) contributed to the high cost of RALP ($16,946). Cryotherapy ($11,215) was more costly than LDR brachytherapy, largely because of increased single-use equipment costs ($6,292 vs $1,921). AS reached cost equivalence with LDR brachytherapy after 7 years of follow-up. CONCLUSIONS: The use of TDABC is feasible for analyzing cancer services and provides insights into cost-reduction tactics in an era focused on emphasizing value. By detailing all steps from diagnosis and treatment through 12 years of follow-up for low-risk prostate cancer, this study has demonstrated significant cost variation between competing treatments.

Pre-treatment MRI minimum apparent diffusion coefficient value is a potential prognostic imaging biomarker in cervical cancer patients treated with definitive chemoradiation.

BACKGROUND: Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) has been studed in several cancers including cervical cancer. This study was designed to investigate the association of DW-MRI parameters with baseline clinical features and clinical outcomes (local regional control (LRC), disease free survival (DFS) and disease specific survival (DSS)) in cervical cancer patients treated with definitive chemoradiation. METHODS: This was a retrospective study approved by an institutional review board that included 66 women with cervical cancer treated with definitive chemoradiation who underwent pre-treatment MRI at our institution between 2012 and 2013. A region of interest (ROI) was manually drawn by one of three radiologists with experience in pelvic imaging on a single axial CT slice encompassing the widest diameter of the cervical tumor while excluding areas of necrosis. The following apparent diffusion coefficient (ADC) values (×10(-3) mm(2)/s) were extracted for each ROI: Minimum - ADCmin, Maximum - ADCmax, Mean - ADCmean, and Standard Deviation of the ADC - ADCdev. Receiver operating characteristic (ROC) curves were built to choose the most accurate cut off value for each ADC value. Correlation between imaging metrics and baseline clinical features were evaluated using the Mann Whitney test. Confirmatory multi-variate Cox modeling was used to test associations with LRC (adjusted by gross tumor volume - GTV), DFS and DSS (both adjusted by FIGO stage). Kaplan Meyer curves were built for DFS and DSS. A p-value < 0.05 was considered significant. Women median age was 52 years (range 23-90). 67 % had FIGO stage I-II disease while 33 % had FIGO stage III-IV disease. Eighty-two percent had squamous cell cancer. Eighty-eight percent received concurrent cisplatin chemotherapy with radiation. Median EQD2 of external beam and brachytherapy was 82.2 Gy (range 74-84). RESULTS: Women with disease staged III-IV (FIGO) had significantly higher mean ADCmax values compared with those with stage I-II (1.806 (0.4) vs 1.485 (0.4), p = 0.01). Patients with imaging defined positive nodes also had significantly higher mean (±SD) ADCmax values compared with lymph node negative patients (1.995 (0.3) vs 1.551 (0.5), p = 0.03). With a median follow-up of 32 months (range 5-43) 11 patients (17 %) have developed recurrent disease and 8 (12 %) have died because of cervical cancer. ROC curves based on DSS showed optimal cutoffs for ADCmin (0.488 × 10(-3)), ADCmean (0.827 × 10(-3)), ADCmax (1.838 × 10(-3)) and ADCdev (0.148 × 10(-3)). ADCmin higher than the cutoff was significantly associated with worse DFS (HR = 3.632-95 % CI: 1.094-12.054; p = 0.035) and DSS (HR = 4.401-95 % CI: 1.048-18.483; p = 0.043). CONCLUSION: Pre-treatment ADCmax measured in the primary tumor may be associated with FIGO stage and lymph node status. Pre-treatment ADCmin may be a prognostic factor associated with disease-free survival and disease-specific survival in cervical cancer patients treated with definitive chemoradiation. Prospective validation of these findings is currently ongoing.

Long term results from a prospective database on high dose rate (HDR) interstitial brachytherapy for primary cervical carcinoma.

OBJECTIVE: Present long-term outcomes in primary cervical cancer treated with external beam and high dose rate interstitial brachytherapy. METHODS: High dose rate (HDR) interstitial (IS) brachytherapy (BT) and external beam (EBRT) were administered from 1992 to 2009 to 315 patients who were unsuitable for intracavitary (IC) BT alone. Histology was 89% squamous cell, 8% adenocarcinoma, and 3% adenosquamous. FIGO stage was I-14%, II-47%, III-34%, and IVA-5%. Median tumor size was 6cm. Lymph node metastases were 26% pelvic and 9.5% para-aortic. Treatment planning was 49% 2D and 51% 3D-CT. The mean doses were central EBRT EQD210 37.3±4.3Gy (sidewall 49.2±3.6Gy) and HDR EQD210 42.3±5.3Gy (nominal 5.4Gy×6 fractions using a mean of 24 catheters and 1 tandem). Total EQD210 mean target dose was 79.5±5.4Gy. Standardized planned dose constraints were ICRU points or D0.1cc bladder 80%, rectum 75% and urethra 90% of the HDR dose per fraction. Morbidity assessment was CTCAEv3. Median and mean follow-up were 50 and 61months (3-234). RESULTS: The 10-year actuarial local control was 87%, regional control 84%, and loco-regional control 77%. Distant metastasis free survival was 66%, cause specific survival 56%, disease free survival 54%, and overall survival 40%. The rates of late grade GU and GI toxicities were 4.8% G3 and 5.4% G4. CONCLUSIONS: Template-guided interstitial can be safely performed to successfully deliver high radiation dose to locally advanced cervix cancer and avoid excessive dose and injury to adjacent vital pelvic organs. We achieved high tumor control with low morbidity in patients who were poor candidates for intracavitary brachytherapy.

Does the addition of targeted prostate biopsies to standard systemic biopsies influence treatment management for radiation oncologists?

OBJECTIVES: To study the management impact that magnetic resonance imaging (MRI)-guided targeted prostate biopsies could provide relative to using only non-targeted systematic biopsies in men with clinically localized prostate cancer (PCa). PATIENTS AND METHODS: A consecutive series of untreated men undergoing Artemis (MRI-ultrasonography fusion) biopsies between March 2010 and June 2013 was evaluated in this retrospective, institutional review board-approved study. Fusion biopsy included MRI-targeted and systematic sampling at the same session. 3-Tesla multiparametric MRI was performed at a median of 2 weeks before biopsy. Patients were included if ≥1 systematic core was found to harbour PCa. The impact of the information obtained from targeted vs systematic biopsies was studied with regard to the following: Gleason score (GS), National Comprehensive Cancer Network (NCCN) risk reclassification, cancer core length, percentage of core positive for tumour involvement, and percentage of positive biopsy cores. RESULTS: The study sample included 215 men (mean ± sd age 66 ± 8 years). The median (range) prostate-specific antigen (PSA) was 6.0 (0.7-181) ng/mL. The mean number of total biopsy samples was 18 (12 systematic and six targeted samples). Of 215 men, 34 (16%) had a higher GS on targeted vs systematic biopsy. A total of 21/183 men (12%) were stratified into a higher NCCN risk group when incorporating targeted biopsy GS results and 18/101 men (18%) were upgraded to intermediate- or high-risk from the low-risk group. Among the 34 men whose cancer severity was upgraded, increases in cancer core length, percentage of tumour involvement and percentage of cores involved were all statistically significant (P < 0.01). CONCLUSION: Targeted prostate biopsy provided information about GS, NCCN risk and tumour volume beyond that obtained in systematic biopsies, specifically increasing the proportions of men in the intermediate- and high-risk groups. Such men may be recommended for additional treatments (pelvic nodal irradiation or hormonal therapy). The appropriateness of changing treatment because of targeted biopsy results is still unclear.

Moving from standardized to personalized boxes and pears in radiation planning for cervical cancer.

PURPOSE OF REVIEW: We reviewed the most recent literature on advancements in external beam radiation therapy, brachytherapy, and stereotactic body radiation therapy (SBRT) in the treatment of cervical cancer. RECENT FINDINGS: There is a growing transition from three-dimensional-conformal radiation therapy to intensity modulated radiation therapy, and from point A-based two-dimensional prescriptions to three-dimensional volume-based prescriptions in image-guided brachytherapy (IGBT). These advances allow dose-escalation to at-risk regions while sparing normal tissues. Implementation of these techniques is resulting in improved local control and decreased toxicity in patients. With increased local control, the predominant pattern of recurrence is now distant failure, opening the door for SBRT as an emerging treatment option for select patients with limited numbers of metastases (oligometastatic state). SUMMARY: The integration of IGBT, as well as dose sculpting with intensity modulated radiation therapy, is improving outcomes in women with locally advanced cervical cancer. The clinical evidence strongly supports moving away from point A-based prescriptions and adopting IGBT techniques. The existing data supporting SBRT for gynecologic oligometastases are more limited and require further research before widespread adoption; however, evidence from other disease sites is promising.

Tumor-height regression rate after brachytherapy between choroidal melanoma gene expression profile classes: effect of controlling for tumor height.

PURPOSE: To evaluate the relationship between choroidal melanoma regression rate and its gene expression profile class after iodine-125 brachytherapy at 3 and 6 months, controlling for baseline tumor height. METHODS: Patients from October 2012 to January 2015 at a single Ophthalmic Oncology Center who had undergone iodine-125 brachytherapy for the treatment of choroidal melanoma and who had a gene expression profile test result obtained from intraoperative fine-needle aspiration biopsy at the time of plaque surgery were retrospectively reviewed. Baseline patient and tumor characteristics were obtained, including tumor height and gene expression profile test result. Tumor height at 3 and 6 months following treatment was obtained. Regression rate was analyzed with two-way analysis of variance to class type and baseline pre-operative tumor height. Class 2 patients were matched to class 1 patients by tumor height and resulting distributions of paired regression rate differences were compared. RESULTS: A total of 114 patients were studied. When preoperative tumor height was controlled for in the comparative analysis, neither group of patients at 3 or 6 months had a significant dependency between gene expression profile class and tumor regression rate. Additionally, class 1 and class 2 patients matched for pre-operative tumor height did not express different regression rates. CONCLUSIONS: Our study adds to a growing body of evidence that tumor regression rate does not necessarily depend on gene expression profile class type in choroidal melanoma after brachytherapy at 3 and 6 months when controlling for baseline tumor height.

23-mm iodine-125 plaque for uveal melanoma: benefit of vitrectomy and silicone oil on visual acuity.

PURPOSE: To review outcomes in mostly large uveal melanoma treated with a 23-mm-diameter iodine-125 plaque, the largest size available at our center, and the influence of vitrectomy and silicone oil 1000 centistokes for radiation attenuation. METHODS: A one-to-one matched case-control comparison was performed. Case patients were treated with a 23-mm-diameter iodine-125 plaque and vitrectomy with silicone oil 1000-cSt placement. Control cases, treated with 23-mm plaque alone, were matched to cases with respect to tumor size and distance from tumor apex to optic nerve and fovea. Postoperative complications, visual acuity and metastasis were reviewed. RESULTS: Twenty case patients with uveal melanoma treated with a 23-mm plaque were identified. The final logMAR vision was 0.83 in case patients and 2.06 in control patients (P = 0.0064); the change from pre-treatment to last follow-up logMAR vision was 0.70 in cases and 1.62 in controls (P = 0.019). Of good vision outcomes, 65 % of cases and 25 % of controls achieved vision ≥20/200 (P = 0.025). Of poor vision outcomes, 35 % of cases and 80 % of controls achieved vision <20/200 (P = 0.0053), and 5 % of cases and 35 % of controls achieved "light perception" or "no light perception" vision (P = 0.044). Thirty-nine of the 40 eyes (98 %) achieved local tumor control. Metastasis occurred in 15 % of cases and 45 % of controls (P = 0.082). CONCLUSIONS: Iodine-125 brachytherapy for mostly large uveal melanoma is effective in achieving local tumor control. Furthermore, combining brachytherapy with vitrectomy and silicone oil 1000-cSt for radiation attenuation significantly improves vision over the use of plaque alone.

Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

PURPOSE: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation with interstitial multicatheter brachytherapy by a cooperative group of institutions. METHODS: From 1992 to 2013, a total of 1356 patients were treated with breast-conserving surgery and adjuvant accelerated partial breast irradiation using interstitial multicatheter brachytherapy. A total of 1131 patients had >1 year of data available to assess oncologic and cosmesis outcomes. Median age was 59 years old (range 22-90 years). Histologies treated included 1005 (73 %) invasive ductal carcinoma and 240 (18 %) ductal carcinoma-in situ. T stages were 18 % Tis, 75 % T1, and 8 % ≥T2. Nodal status was 73 % N0 and 6 % N1a. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was positive in 83, 70, and 6 %, respectively. Cox multivariate analysis for local control was performed using histology, age, estrogen receptor status, tumor size, grade, margin, and nodal status. RESULTS: The mean (SD) follow-up was 6.9 years (4.3). The 10-year actuarial risk (95 % confidence interval) of an ipsilateral breast tumor recurrence was 7.6 % (5.6-10.1). Other 10-year actuarial risks (95 % confidence interval) were regional failure 2.3 % (1.4-3.7), distant metastasis 3.8 % (2.5-5.7), cause-specific survival 96.3 % (94.2-97.6), overall survival 86.5 (83.0-89.3), and new contralateral cancers 4.6 % (3.0-6.9). On multivariate analysis, high grade (hazard ratio 2.81) and positive margin status (hazard ratio 18.42) were the only two significant variables associated with an increased risk of local recurrence. Physician-reported cosmesis was excellent/good in 84 % (98 of 116) of patients with >5 years of follow-up. CONCLUSIONS: This is the largest report of outcomes with interstitial breast brachytherapy. This treatment resulted in excellent long-term local control and cosmesis outcomes.

Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3.

INTRODUCTION: Uveal melanoma is a rare intraocular tumor with heterogeneous biological behavior, and additional noninvasive markers that may predict outcome are needed. Diffusion- and perfusion-weighted imaging may prove useful but have previously been limited in their ability to evaluate ocular tumors. Our purpose was to show the feasibility and potential value of a multiparametric (mp-) MRI protocol employing state of the art diffusion- and perfusion-weighted imaging techniques. METHODS: Sixteen patients with uveal melanoma were imaged with mp-MRI. Multishot readout-segmented echoplanar diffusion-weighted imaging, quantitative dynamic contrast-enhanced (DCE) MR perfusion imaging, and anatomic sequences were obtained. Regions of interest (ROIs) were drawn around tumors for calculation of apparent diffusion coefficient (ADC) and perfusion metrics (K (trans) , v e , k ep , and v p ). A generalized linear fit model was used to compare various MRI values with the American Joint Commission on Cancer (AJCC) tumor group and monosomy 3 status with significance set at P < 0.05. RESULTS: mp-MRI was performed successfully in all cases. MRI tumor height (mean [standard deviation]) was 6.5 mm (3.0). ROI volume was 278 mm(3) (222). ADC was 1.07 (0.27) × 10-3 mm(2)/s. DCE metrics were K (trans) 0.085/min (0.063), v e 0.060 (0.052), k ep 1.20/min (0.32), and v p 1.48 % (0.82). Patients with >33 % monosomy 3 had higher K (trans) and higher v e values than those with disomy 3 or ≤33 % monosomy (P < 0.01). There were no significant differences between ADC (P = 0.07), k ep (P = 0.37), and v p with respect to monosomy 3. CONCLUSION: mp-MRI for ocular tumor imaging using multishot EPI DWI and quantitative DCE perfusion is technically feasible. mp-MRI may help predict monosomy 3 in uveal melanoma.