bluuebunny/crossref_metadata_2025 huggingface dataset:
Front-line management patterns in the prospective metastatic renal cell cancer (MaRCC) registry.
Authors: Harrison Michael Roger , Bhavsar Nrupen Anjan , Wolf Steven Paul , Costello Brian Addis , Stadler Walter Michael , Hammers Hans J. , Vaishampayan Ulka N. , Appleman Leonard Joseph , Tsao Che-Kai , Creel Patricia A. , Samsa Greg P. , Richardson Eric M. , Johnson Kathleen A. , Borham Azah , George Daniel J.
Published: February 2017

617

Background: Over the past decade, seven agents were approved for metastatic renal cell carcinoma (mRCC) leading to a rapidly evolving clinical landscape. Clinical trials addressing treatment efficacy, sequencing, and other questions may continue to impact management decisions. Furthermore, our prior retrospective experience indicates a significant proportion of pts may not receive systemic therapy in the first year after diagnosis with metastatic disease. This analysis describes contemporary patterns of care in the first 109 real world pts enrolled in a multicenter, prospective, observational registry. Methods: MaRCC Registry will enroll 500 pts from up to 60 US academic (ACAD) and community (COMM) sites with ~2 years of recruitment and ≥ 3 years of follow-up. Key inclusion criteria are age ≥ 18 years and diagnosis of mRCC with no prior systemic therapy (STx) for mRCC at study entry. Pts currently not on STx but who are being observed are permitted. Key endpoints include descriptive characteristics of treatments (e.g. treatment agents, sequence, duration, reasons for therapy choice and discontinuation), treatment effectiveness (e.g. overall response rate, progression free survival, overall survival), quality of life (PROs), medication adherence, and health resource utilization. Results: At data cutoff, 105 pts have been accrued with known STx status; median age 64 (Q1-3 range, 56-70); 66% male; 75% ACAD; 87% clear cell histology; and 31% stage IV at diagnosis. Initial management strategies are shown in the table. The initial management decision after accrual was to defer systemic therapy (Def STx) in 40% (N=44). In ACAD and COMM sites, Def STx percentages were 38% and 48% respectively. Baseline demographics and clinical characteristics were not notably different between Def STx pts and those treated with STx. Conclusions: In our prospective registry, we have identified a large percentage of pts who initially received Def STx. In the context of contemporary pts undergoing investigational and standard of care STx, we will describe the management and outcomes of the Def STx population. [Table: see text]
Missing the mark? Prostate cancer upgrading by systematic biopsy over fusion biopsy.
Authors: Muthigi Akhil , George Arvin Koruthu , Iyer Amogh , Kongnyuy Michael , Kadakia Meet , Chelluri Raju , Mertan Francesca , Frye Thomas P , Kilchevsky Amichai , Sidana Abhinav , Krane Spencer , Su Daniel , Merino Maria J , Turkbey Ismail B. , Choyke Peter L. , Wood Bradford J. , Pinto Peter A.
Published: February 2017

62

Background: Multiparametric MRI (mpMRI) and fusion biopsy (FBx) detect more high risk prostate cancer (CaP) and less low risk CaP than standard systematic biopsy (SBx). However, there remains a small subset of patients where SBx captures higher grade disease than FBx. We aim to identify potential reasons for failure of FBx biopsy in detection of clinically significant (CS) CaP. Methods: A review was performed of a prospectively maintained database of patients undergoing mpMRI followed by FBx and SBx in the same session from 2007−2014. Patients upgraded to higher risk disease based on SBx results relative to FBx were identified. Independent re−review of MR imaging in this subset was conducted to identify potential proximity between MR targets and SBx region which revealed higher risk CaP. Univariate analysis was performed to determine association of patient, MRI, and pathologic characteristics with upgrading by SBx. Results: We identified 1003 total patients who underwent mpMRI and biopsy, of which 564 were found to have CaP (56.2%). Upgrading based on SBx occurred in 137/564 (24.3%) patients, of which only 55 (9.8%) were to intermediate (high volume 3+4) [N = 37, 6.5%] or high risk CaP ( ≥ 4+3) [N = 18, 3.2%]. 41 of 55 patients (75%) had a lesion identified by mpMRI with FBx in the same sextant in which SBx biopsy revealed intermediate or high risk CaP. On univariate analysis, higher prostate volume (48cc vs 42cc, p < 0.001) and lower percent core involvement (20% vs. 58%, p < 0.001) were associated with upgrading by SBx. Conclusions: MRI rarely misses CS CaP and FBx, if accurate, should reflect the true disease state. Most gleason upgrades by SBx were to low risk, low volume CaP. In patients upgraded by SBx to CS CaP, mpMRI identified a targetable lesion in proximity to the SBx sextant in a majority of patients. FBx failure may be related to suboptimal imaging or biopsy related inaccuracy including registration error, miscalculation of target location, or inadequate lesion sampling. Other possibilities include presence of tumor heterogeneity, multi−focality within the same sextant, or low volume disease. Future studies with biopsy mapping on MRI will provide insight into mechanisms of failure in patients with overlapping target and sextant sampling.
Very small nuclear circulating tumor cell (vsnCTC) as a putative biomarker for visceral metastasis in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Chen Jie-Fu , Ho Hao , Hodara Elisabeth , Go Ann , Ureno Alexander , Kaufman Elizabeth Taryn , Sievert Margarit , Chung Leland WK , Ke Zunfu , Tseng Hsian-Rong , Posadas Edwin M.
Published: February 2017

64

Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) who develop visceral metastasis (VM) have a poorer clinical outcome in comparison to those without VM. Their clinical course is aggressive and culminates in organ failure as this process is often discovered late in the disease course. There are no existing tests that identify men at risk for VM. Our team has identified an association between the presence of very small nuclear circulating tumor cells (vsnCTCs) and VM. We hypothesized that vsnCTC that can predict the development of VM and monitor the response to anticancer treatment. Methods: In our database we identified mCRPC patients who had progressed through next generation hormonal maneuvers such as abiraterone, enzalutamide, or an equivalent drug. Serial blood specimens were used for vsnCTC enumeration using published methods. The vsnCTC counts were related to the presence and development of VM as well as the response to anticancer treatment. Results: Blood specimens were identified from 28 patients who met the eligibility criteria; 16/28 patients presented with VM and 12/28 had bone-only disease at their first CTC enumeration. Five out of 12 non-VM patients developed VM during follow-up, and vsnCTCs were detected 86-196 days prior to radiographic detection of VM (true positive); 3/12 had vsnCTCs detected but no VM was found by the time of analysis (false positive). None of the vsnCTC(-) patients developed VM. vsnCTCs were detected in 21/21 VM patients compared to 3/12 non-VM patients. Reduction of vsnCTC count occurred at initiation of anticancer treatment; transition from vsnCTC(-) to vsnCTC(+) was seen prior to progression under the treatment. Conclusions: vsnCTC is associated with the presence of VM and is a potential biomarker for predicting the development of VM and monitoring the treatment response in mCRPC. Transition from vsnCTC(-) to vsnCTC(+) was associated with the development of VM and progression under the treatment.
Survival outcomes of dose-escalated external beam radiotherapy (DE-EBRT) versus combined brachytherapy for intermediate- and high-risk prostate cancer using the National Cancer Data Base.
Authors: Amini Arya , Jackson Matthew Wayne , Yeh Norman , Waxweiler Timothy V , Jones Bernard , Maroni Paul , Kavanagh Brian D. , Raben David
Published: February 2017

7

Background: The purpose was to evaluate survival outcomes between dose-escalated external beam radiotherapy (DE-EBRT) versus EBRT plus brachytherapy for intermediate- and high-risk prostate cancer, using the National Cancer Data Base (NCDB). Methods: Patients with cN0M0 prostate cancer treated from 2004-2006, with available data for radiation therapy dose were included. Radiation treatment comparison groups were the following: EBRT alone (75.6-81 Gy) and EBRT (40-50.4 Gy) plus brachytherapy, with EBRT delivered in 1.8-2.0 Gy per fraction. Eligible patients had known T-stage, prostate-specific antigen, Gleason score, and receipt of androgen deprivation therapy. Results: A total of 20,279 patients with intermediate (n = 12,617) and high-risk (n = 7,662) prostate cancer were included; 71.3% (n=14,452) received EBRT alone, 28.7% (n = 5,827) received EBRT plus brachytherapy. Median follow up was 82 months (range, 3-120 months) and median age was 70 years (36-90 years). By multivariate analysis, EBRT plus brachytherapy had a significantly improved survival benefit (hazard ratio [HR], 0.75; p < 0.001) compared to EBRT alone (75.6-81 Gy); this significance remained consistent for both intermediate-risk (HR, 0.73; p < 0.001) and high-risk (HR, 0.76; p < 0.001) when analyzed separately. On subset analysis however, EBRT plus brachytherapy did not have a significant survival improvement (HR, 0.91; p = 0.083) when compared to very high dose EBRT alone (79.2-81 Gy) for all patients combined; this persisted for intermediate-risk (HR, 0.73; p = 0.062) and high-risk (HR, 0.93; p = 0.400) patients when analyzed separately. Conclusions: Patients receiving EBRT plus brachytherapy had improved survival compared to DE-EBRT alone (75.6-81 Gy) for intermediate- and high-risk prostate cancer. When comparing EBRT plus brachytherapy versus very high dose EBRT alone (79.2-81 Gy), this survival advantage disappeared. Given these findings, intermediate- and high-risk prostate cancer patients may benefit from EBRT plus brachytherapy compared with DE-EBRT alone; however, very high doses of EBRT may also be an equivalent option.
Health-related quality of life changes due to high-dose rate brachytherapy, low-dose rate brachytherapy, or intensity-modulated radiation therapy for prostate cancer.
Authors: Strom Tobin Joel Crill , Cruz Alex , Figura Nicholas , Shrinath Kushagra , Nethers Kevin , Mellon Eric Albert , Fernandez Daniel Celestino , Saini Amarjit , Hunt Dylan , Heysek Randy , Wilder Richard
Published: February 2017

72

Background: To compare urinary, bowel, and sexual health-related quality of life (HRQOL) changes due to high-dose rate (HDR) brachytherapy, low-dose rate (LDR) brachytherapy, or intensity modulated radiation therapy (IMRT) monotherapy for prostate cancer. Methods: Between January 2002 and September 2013, 413 low-risk or favorable intermediate-risk prostate cancer patients were treated with HDR brachytherapy monotherapy to 2,700-2,800 cGy in two fractions (n=85), iodine-125 LDR brachytherapy monotherapy to 14,500 cGy in one fraction (n=249), or IMRT monotherapy to 7,400-8,100 cGy in 37-45 fractions (n=79) without pelvic lymph node irradiation. No androgen deprivation therapy was given. Patients used an International Prostate Symptoms Score questionnaire, an Expanded Prostate cancer Index Composite-26 bowel questionnaire, and a Sexual Health Inventory for Men questionnaire to assess their urinary, bowel, and sexual HRQOL, respectively, pre-treatment and at 1, 3, 6, 9, 12, and 18 months post-treatment. Results: Median follow-up was 32 months. HDR brachytherapy and IMRT patients had significantly less deterioration in their urinary HRQOL than LDR brachytherapy patients at 1 and 3 months post-irradiation. The only significant decrease in bowel HRQOL between the groups was seen 18 months following treatment, at which point IMRT patients had a slight, but significant, deterioration in their bowel HRQOL compared with HDR and LDR brachytherapy patients. HDR brachytherapy patients had worse sexual HRQOL than both LDR brachytherapy and IMRT patients following treatment. Conclusions: IMRT and HDR brachytherapy cause less severe acute worsening of urinary HRQOL than LDR brachytherapy. However, IMRT causes a slight, but significant, worsening of bowel HRQOL compared with HDR and LDR brachytherapy.
The impact of subsequent metastasis on medical costs in Medicare patients with prostate cancer.
Authors: Li Tracy , Shore Neal D. , Mehra Maneesha , Todd Mary Beth , Saadi Ryan , Leblay Gaetan , Griffiths Robert
Published: February 2017

81

Background: The objective of this study was to estimate the direct medical costs of secondary metastases in prostate cancer (PC) patients initially diagnosed with locoregional disease. Methods: We used data from the United States Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims to identify a cohort of PC patients initially diagnosed with locoregional disease between 2000 and 2011, who were age ≥ 66 at diagnosis, and who first had a diagnosis of metastasis (index date) ≥ 4 months after PC diagnosis (cases). We matched each case to up to four controls (patients without metastasis) on baseline patient characteristics to assess the incremental impact of developing metastasis. A “match date” corresponding to the index date of the case was constructed for each control. Cases and controls were followed from up to 12 months before and up to 12 months after metastasis. Medicare claims were used to calculate the average total cost per month in the cases and controls. Monthly costs also were stratified according to place and type of service, e.g. inpatient, outpatient, and by whether costs pertained to cancer services, i.e. chemotherapy or androgen deprivation therapy (ADT), other services with an ICD-9 code for cancer, or other care. Results: The cohort consisted of 10,370 cases and 39,200 controls, with a mean age at baseline of 79 years in both groups. The median time to subsequent metastasis (cases) was 37 months and 85% had bone metastasis. In the control group, total costs remained stable throughout the observation period, averaging $1,354/month before and $1,173 12/month after matched index date. In the cases, costs were similar to the controls from -12 to -6 months before the index date. Thereafter, medical costs rose sharply to $11,982 in the month of diagnosis of metastasis (index date), and then declined but stayed > $2,000/month higher than the control for the remainder of the observation period. Expenses from inpatient, physician services, outpatient, and skilled nursing facility accounted for the largest proportions of total costs. Conclusions: Developing metastasis in Medicare PC patients results in substantial additional costs to the healthcare system.
E2809: Androgen receptor (AR) modulation by bicalutamide (Bic) and MK-2206 (MK) in men with rising PSA at high-risk of progression after local prostate cancer (PC) treatment.
Authors: Ferrari Anna C. , Chen Yu-Hui , Hudes Gary R. , Carducci Michael Anthony , Antonarakis Emmanuel S. , Hahn Noah M. , Wong Yu-Ning , DiPaola Robert S.
Published: February 2017

9

Background: Men with PSA recurrence and fast PSA doubling time (PSADT) are at high risk of progression. While castration effectively decreases PSA and delays metastases, it compromises heath and quality of life without clear survival benefit. E2809 tested whether blocking Akt with MK alone or together with the AR using Bic, would be more effective than Bic alone to suppress AR activity without castration. Methods: 108 PSA-recurrent N0 M0, non-castrate PC patients (pts) with PSADT<12 months (mo) and PSA>2ng/mL; were randomized 1:1 to 11, 4-week (wk) treatment (tx) cycles (cy), up to18cy: arms (A) cy1-3, observation, cy 4-11, Bic 50 mg daily; (B) cy1-3 MK 200 mg once wk orally, cy 4-11 MK+Bic. Endpoints: Primary: proportion of pts with PSA <0.2 by cy11 (90% power to detect 45% vs. 20% using 0.1 level one-sided Fisher’s exact test); Secondary, PSA decline: ≥85%; nadir levels before and after Bic. Toxicity (Tox). Results: 54 pts/arm. Baseline characteristics (median (m) or %, A/B): age, 66/67 years; Gl>7 81/81%; >T2b 98/86%; prostatectomy, 81/75%; radiation, 30/31%; previous castration, 43/46%; testosterone, 302/333 ng/dL; PS 0, 94/93%; mPSA 5.1/6.1ng/dL; PSADT<9 mo, 87/81%, <3 mo 24/37%; Tox. Grade(G)/n: G4: A, 0; B, 2 (embolism, hyperglycemia). G3: A, 1(LFTs); B, 32, 60% (rash 20, hyperglycemia 5, low lymphs, 5; hypertension, 4). At 23.9 mo follow-up, 1 death B. Tx . A: 4 no tx; 14 (26%) started Bic early; 9 (16.7%) stopped <11cy without SAE’s; 41 (76%) completed 11cy, 23 (43%) 18cy. B: 7 (13%) started Bic early; 21 (39%) stopped <11cy due to AE’s in 14 (66%) cases; 32 (59%) completed 11cy, 14 (26%) 18cy. PSA<0.2 at 44wks (cy11): A, 6 (11.1%); B, 8 (14.8%), p=0.39. Among evaluable pts, PSA ≤0.2 occurred only after Bic: A: 10/49 pts (20.4%); B: 16/45 pts (35.6%), p=0.08. Conclusions: Overall, by intent to treat analysis at 44 wks, MK alone had no effect on PSA, nor did it increase response to Bic by any set criteria. High MK discontinuation due to rash before cy11 may have blunted the significance of a higher proportion of evaluable pts on MK+Bic achieving PSA ≤0.2ng/ml compared to Bic alone. Clinical trial information: 01251861.
Prostate cancer detection rates of negative MP-MRIs.
Authors: Lu Amanda , Nawaf Cayce , Weinreb Jeffrey , Rosoff James , Schulam Peter , Humphrey Peter , Levi Angelique , Sprenkle Preston
Published: February 2017

91

Background: Increased lesion suspicion score on MRI is known to be associated with increased grade of prostate cancer. However, the negative predictive value (NPV) of MRI is still being investigated. To determine the NPV of mpMRI, we evaluated the frequency of prostate cancer (CaP) detection by 12-core template mapping biopsy (Mbx) in men whose mpMRI showed no suspicious regions. Methods: 374 men undergoing MRI-US fusion biopsy from 12/2012 to 06/2015 were enrolled in an IRB-approved database and met inclusion criteria for this study. The mpMRI sequences T2-weighted, diffusion-weighted imaging, and dynamic contrast enhancement were used to identify and classify targets as low, medium, and high suspicion. Men with negative mpMRI received a template 12-core template mapping biopsy. Only patients with complete mpMRI sequences were included. Results: 53 men with a negative MRI were identified (mean age=63.5 years, PSA=7.53 ng/mL, mean prostate volume=67.2 mL). The NPV of negative MRI was 64.2% for any cancer and 96.2% for clinically significant cancer (Gleason≥7). Men on active surveillance had the highest CDR 56.3%, compared to 38.9% for biopsy-naive men, and 15.8% for men with prior negative biopsy (Figure 1). Clinically significant CaP was found in two patients: Gleason 4+3 in a patient on Active Surveillance, and 4+4 in a biopsy naïve patient. Conclusions: Negative MRI has a high NPV (96%) for clinically significant CaP found in 12-core template mapping biopsy. If we did not biopsy mpMRI negative men, we would have missed 16 patients with Gleason 6 and 2 patients with ≥ Gleason 7. Clinicians can use this information in patient counseling to discuss the likelihood of detecting significant cancer – though these findings should be reproduced widely before a negative MRI is used to recommend against biopsy. Sources of funding: NIH-National Institute of Diabetes and Digestive and Kidney Diseases [Table: see text]
5α-reductase inhibitors and the risk of grade reclassification for men with long-term follow-up on active surveillance for prostate cancer.
Authors: Finelli Antonio , Timilshina Narhari , Komisarenko Maria , Sowerby Robert , Hamilton Robert James , Zlotta Alexandre , Fleshner Neil Eric
Published: February 2017

92

Background: The role of 5α-reductase inhibitors (5-ARIs) in prostatic diseases remains controversial because of an FDA black box label. We have previously published on the impact of 5-ARIs in men managed with active surveillance (AS), demonstrating their protective effect against progression. However, the long-term safety of 5-ARIs in the setting of AS has never been described, thus we sought to assess this. Methods: This is a single-institution, prospectively maintained, retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on AS for PCa. Pathologic progression was evaluated and defined as Gleason score > 6, maximum core involvement > 50%, or more than 3 cores positive on a follow-up prostate biopsy. Time dependent covariate analysis to account for time on AS but not on 5-ARI was conducted to diminish the likelihood of overestimating the benefit. To account for differences in prostate volume at baseline between 5-ARI and non-5-ARI groups sensitivity analyses were performed, restricting men in the non-5-ARI group to those with larger glands (volume > 40 ml). Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression. Results: The original cohort of 288 men on AS were analyzed. The median follow-up was 61.2 months (IQR: 29.8-95.24) with 124 men (43%) experiencing pathologic progression and 119 men (41.3%) abandoning AS. Men taking a 5-ARI experienced a lower rate of pathologic progression (24.3% vs 49.1%; p < 0.001) and were less likely to abandon AS (25.7% vs 46.3%; p = 0.002). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (HR: 2.56; 95% confidence interval, 1.32-5.02). Sensitivity analyses done to account for gland size demonstrated that lack of 5-ARI use was still predictive of progression (HR: 2.76; CI, 1.45–5.25; p = 0.002). Importantly, 5-ARI use was not associated with increased risk of high-grade prostate cancer. Conclusions: 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of AS in men with median follow-up of 5 years.
Salvage radiation therapy after radical prostatectomy: Contribution of a dose escalation to macroscopic local relapses.
Authors: Selmaji Imad Eddine , Udrescu Corina , Brahmi Tristan , Samlali Hamza , Lapierre Ariane , Enachescu Ciprian , Ruffion Alain , Chapet Olivier
Published: February 2017

e634

Background: Salvage radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer using 66 Gy may not be enough to treat macroscopic disease. The presence of a macroscopic nodule on the MRI could justify a focal dose escalation. This study evaluates the tolerance and efficacy of a new technique of irradiation including a focal boost to the nodule. Methods: Between 2011 and 2015, 14 patients, with a macroscopic relapse diagnosed on the MRI, underwent targeted MRI-guided biopsies. Three gold markers were implanted into the prostatic bed for a more accurate MRI/CT fusion and image guided IMRT. A dose of 60 Gy was delivered to the prostatic bed followed by a dose escalation to 72Gy on the macroscopic nodule. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated using the CTCAE v4. PSA level and late toxicities were assessed at 1 month and then every 6 months for 3 years. Results: The mean follow-up was 26.2 [18 – 36] months. Two patients had a biochemical failure after salvage RT (one bone metastasis and one lymph node recurrence). The local control rate was 100% and the biochemical control rate was 85.7%. Results for acute and late toxicities are summarized in the table. One patient presented with grade 2 urinary toxicity during the prostatic bed irradiation which lowered to grade 1 when the dose was focalized to the nodule. No grade 2 acute GI toxicity was seen. All late GI and GU toxicities were grade 1. Conclusions: Dose escalation to the macroscopic nodule visible on MRI is feasible using an IMRT-IGRT approach with gold makers. This technique allows a perfect initial local control at 3 years with a good tolerance. [Table: see text]
Focal or whole gland salvage prostate brachytherapy with iodine seeds with or without a rectal spacer for a post EBRT local failure: How best to spare the rectum?
Authors: Guimas Valentine , Quivrin Magali , Bertaut Aurelie , Martin Etienne , Mazoyer Frederic , Maingon Philippe , Cormier Luc , Crehange Gilles
Published: February 2017

e636

Background: Salvage prostate permanent implant (sPPI) for post radiation local failures provides high rates of biochemical control. The cumulative dose delivered to the prostate and the rectum when taking into account the dose from the primary irradiation is still unknown. Besides cancer control, the primary goal of sPPI should be to protect the rectum in order to avoid any rectal fistula in the long term. Methods: We reviewed the post implant CT-based dosimetry of 18 selected patients who underwent sPPI with 125I seeds for an isolated biopsy-proven local failure several years after external beam radiation therapy (EBRT). Ten patients had a whole prostate sPPI and 8 patients had a multi-parametric MRI-based focal sPPI. Eight patients had an injection of hyaluronic acid (HA) gel in the prostate-rectum space. The BED of the primary EBRT and the BED of the sPPI were calculated using several a/b ratios (1.5, 2, 3, 5 and 10) and t1/2 (1h for the prostate and 0.3h for the rectum). Comparisons of BED parameters and doses delivered to the rectum according to the use of HA gel, prostate irradiation (whole gland versus focal) were performed using Wilcoxon exact test. Results: The median dose received by 90% of the prostate (D90) was 65.0 Gy [12.0 - 107.2] and the median prostate volume receiving 100% of the prescribed dose (V100) was 45.3% [14.4 - 98.3]. The median D90 and the median V100 for the index lesion were 162.0 Gy [139.4 - 199.1] and 96.1% [88.4 – 100.0], respectively. The median cumulative Biological Equivalent Dose (BED) after EBRT+sPPI for the prostate and the rectum were higher for patients treated on whole gland versus patients treated with focal sPPI (313.5 Gy2 vs 174.4 Gy2, p = 0.06 and 258.1 Gy3 vs 172.6 Gy3, p < 0.01, respectively). The median D0.1 cc for the rectum was significantly lower for patients who had HA gel: 63.3 Gy [29.0 - 78.3] compared to patients with no gel: 83.9 Gy [34.9 – 180.0] (p = 0.04). Conclusions: Focal sPPI provided lower cumulative prostate and rectum BED when compared to whole gland plans. D0.1cc delivered to the rectum was significantly lower after sPPI with HA gel while it was not different between focal or whole gland plans.
A retrospective feasibility analysis of biweekly reduced dose docetaxel in Korean patients with castration-resistant, metastatic prostate cancer.
Authors: Cho Jinhyun , Yoo Kwai Han , Jung Ki Sun , Song Haa-na , Kim Hae Su , Lee Su Jin , Lim Ho Yeong , Park Se Hoon
Published: February 2017

e638

Background: The aim of this retrospective study was to evaluate clinical outcomes of biweekly 40 mg/m2 docetaxel plus prednisolone, as compared with standard 3-weekly regimen in Korean patients with castration-resistant prostate cancer (CRPC). Methods: We retrospectively reviewed the medical records of 48 patients with metastatic CRPC who were consecutively treated with docetaxel plus prednisolone as first-line chemotherapy between Jan 2012 and Dec 2014 at Samsung Medical Center (Seoul, Korea). Prior to the adoption of a biweekly regimen in Oct 2013, our institutional standard chemotherapy was docetaxel 75 mg/m2 every 3 weeks for patients with CRPC (n = 24). After Oct 2013, all chemotherapy-naïve CRPC patients received 40 mg/m2 biweekly regimen (n = 24). The primary end point was the PSA response, defined as a greater than 50% decline in PSA levels from baseline. Results: The baseline characteristics of the patients were similar in the two treatment groups. The most common cause of treatment discontinuation was disease progression: 17 (71%) in 3-weekly group and 20 (82%) in biweekly group. PSA responses were observed in 12 (50%) and 11 (46%) patients in the 3-weekly and biweekly groups, respectively. Time-to-failure (TTF, 4.5 versus 3.9 months) and time-to-progression (TTP, 5.0 versus 4.2 months) were statistically similar between the 3-weekly and biweekly groups, respectively. In 3-weekly group, the most commonly observed toxic effects were anemia and neutropenia. Whereas, in biweekly group, fatigue and nail changes were the most commonly observed toxic effects. Conclusions: Within the limitation of a retrospective study, biweekly reduced dose docetaxel regimen is active and well-tolerated in Korean patients with metastatic CRPC.
Perspective of young breast cancer survivors (BCS) on fertility preservation (FP) referral.
Authors: Seminsky Maureen , Yee Samantha , Glass Karen , Foong Shu , Kennedy Erin Diane , Warner Ellen
Published: February 2017

113

Background: Despite ASCO recommendations (2006, 2013), young cancer patients are frequently not spoken to about the potential effects of treatment on future fertility and are denied the option of FP. Last year we began a 5 year study (SPOKE: Surgeon and Patient Oncofertility Knowledge Enhancement) to increase FP discussion and referral rates of Canadian breast surgeons. To design effective interventions, in addition to interviewing and surveying surgeons we conducted in-depth interviews with young BCS. Methods: Thirty minute semi-structured telephone interviews were conducted with BCS diagnosed < age 40 to explore their oncofertility experiences and their recommendations for future patients. Eligible BCS were recruited by oncologists and fertility specialists. A patient sample was deliberately chosen to reflect diversity of tumor stage, patient demographics and fertility experiences. A $20 incentive was given to each interviewee. Interviews were audio-recorded, transcribed verbatim and the data analyzed using qualitative methods. Subject recruitment was terminated when saturation of themes was obtained. Results: Fifteen BCS from 5 provinces, mean age 32 were interviewed. At diagnosis mean age was 29 with 8 (53%) single, 13 (87%) nulliparous, and 87% receiving adjuvant chemotherapy. At diagnosis all but 1 BCS had either definitely (60%) or possibly (33%) wanted (additional) children but only 8 of the 14 (57%) had been referred for a FP consult. Common recommendations were: discussing fertility as soon as possible after diagnosis to optimize time for decision-making; providing up-to-date information about the various FP options prior to the consult; and encouraging patients ambivalent about future childbearing to pursue FP. Conclusions: Despite the perception by many surgeons that patients are not psychologically able to handle information about fertility and FP at the time of their diagnosis, the majority of BCS interviewed thought that early fertility discussion by the surgical team was essential. SPOKE will include knowledge translations interventions for surgeons, and the creation of a FP information ‘toolbox’ with separate versions for surgeons and patients. Funded by the CBCF and CIHR.
Introducing medical students to survivorship care through an elective oncology summer program.
Authors: McKillip Ryan Patrick , Hahn Olwen Mary , Sulai Nanna Helen , Rosenberg Carol A. , Olopade Olufunmilayo I. , Arora Vineet M , Golden Daniel William
Published: February 2017

12

Background: Advancing the quality of cancer care requires that physicians be trained in survivorship care. An oncology seminar series was designed and implemented for first year medical students to improve their knowledge of oncologic disciplines, including survivorship care, by educating them about these disciplines from both a research and clinical perspective. Methods: First year medical students (MS1s) at a single United States medical school were invited to participate in the Scholars in Oncology-Associated Research (SOAR) summer program, which included a series of 10 lectures to provide a general survey of how clinical care, basic sciences, and social sciences apply to oncology as a multidisciplinary specialty. Lectures included topics specific to cancer genetics, medical, surgical, and radiation oncology, hospice/palliative medicine, and survivorship care. The students also attended a multidisciplinary tumor board and had the opportunity to shadow a pharmacist, radiation therapist, or palliative care advanced practice nurse. Students completed self-assessments of their understanding of oncology and its related disciplines before and after SOAR. Likert-type scores were 1 = not at all, 2 = somewhat, 3 = moderately, 4 = quite, and 5 = extremely and are reported as median [interquartile range]. Results: Eighteen students successfully completed the SOAR program out of 21 that initially enrolled. 20 pre- and 14 post-assessments were completed. Student self-reported understanding of oncology as a clinical discipline (2[2-3] vs. 4[4-4] p < .01) and as a research discipline (3[2-3] vs. 4[4-4] p < .01) improved after SOAR. Student understanding of survivorship care as a clinical discipline (1[1-2] vs. 2.5 [1-4] p = .02) and as a research discipline (1[1-1] vs. 2[1-3] p < .01) also improved. All students indicated they would be “quite” or “extremely” likely to recommend SOAR to future students. Conclusions: A structured didactic introduction to oncology, SOAR, was successfully piloted. MS1s report improved understanding of oncology and survivorship care as clinical and research disciplines. Future work will focus on expanding SOAR to a larger audience.
A 10-year age-related survival analysis on cytoreductive surgery in stage IIIC-IV ovarian cancer: Elderly versus younger women.
Authors: Ruscito Ilary , Gasparri Maria Luisa , Crispino Stefania , La Russa Chiara , Marchetti Claudia , Di Donato Violante , Palaia Innocenza , Perniola Giorgia , Musella Angela , Muzii Ludovico , Benedetti Panici Pierluigi
Published: February 2017

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Background: Approximately half of women diagnosed with advanced ovarian cancer (AOC) is over 65 years old. According to WHO,65 years is the cut-off age for distinguishing elderly individuals from younger people. Aim of the study was to analyze, in a 10-year retrospective series, the age-related differences in perioperative outcome of cytoreductive surgery for stage IIIC-IV ovarian cancer, identifying in ≥ 65y and < 65y patients(pts)the clinicopathological factors associated with poor prognosis. Methods: 167pts with primary epithelial AOC FIGO stage IIIC-IV underwent cytoreduction and platinum-based chemotherapy from 2005 to 2015 at “Sapienza” University of Rome. Pts ≥ 65 and < 65 years were compared regarding surgical outcome, clinicopathological variables and prognosis. Results: Median age was 56 years(19-87);50 pts (29.9%) were ≥ 65y, whereas 117 pts(70.1%) were younger.42%(21/50) of pts in elderly group and 39%(46/117) in younger group received neoadjuvant chemotherapy followed by interval debulking surgery. No residual tumor was achieved in 82% of elderly pts and in 82.9% of younger pts (p > 0.05).No differences between the two groups were found in terms of mean operative time, mean number of blood units transfused, mean postoperative stay and number of pts requiring intensive care unit stay. The perioperative complications rate was 16% in elderly group and 10.2% in younger pts(p > 0.05).The 60-day postoperative mortality was 2%for elderly and 0.8%for younger pts(p > 0.05).The 10y-PFS was 11.6% vs 15.2%(p = 0.84) and the 10y-OS was 16.9% vs 21.4%(p = 0.60) in elderly and younger pts, respectively. Multivariate analysis showed that age itself was not a prognostic factor for OS but in < 65y pts BMI had an independent prognostic significance (HR:4.97;CI 95%:2.09-11.83),together with residual tumor, which was confirmed to be an independent prognostic factor also in elderly pts(HR = 7.33;CI 95% = 1.30-41.33). Conclusions: Elderly pts with AOC showed a similar perioperative outcome compared to younger pts. In ≥ 65y pts, residual tumor was the only variable impacting significantly survival, while in pts < 65y, BMI was also found to be an independent prognostic factor for OS.
A comparison of chemotherapy-induced peripheral neuropathy assessment tools in patients receiving neurotoxic chemotherapy.
Authors: Ramnarine Sabrina , Williams Linda J , Dougherty Patrick M. , Fallon Marie T
Published: February 2017

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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a challenging toxicity with significant sequelae impacting prognosis and quality of life. Clinical presentation although predominantly sensory can include motor and autonomic dysfunction. As there is no standardised approach to the diagnosis and assessment of CIPN, characterisation of symptoms can be problematic. This study aims to investigate the relationship between various CIPN assessment tools in gynaecological, colorectal and lung cancer patients receiving neurotoxic chemotherapy. Methods: Patients with the above cancers receiving chemotherapy (platinum and/or taxanes) were assessed prospectively every 3 weeks for a cumulative total of 159 cycles. Prior to each cycle the following tools were utilised: European Organization for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 questionnaire, MD Anderson Symptom Inventory (MDASI) and associated descriptors of sensory disturbance/pain. Spearman’s correlation coefficients were used to compare these tools with the most commonly measured CIPN diagnostic tool, the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). Results: The EORTC sensory, motor subscales and total scores were highly correlated as expected. MDASI, question 13 (severity of numbness or tingling at its worst) was most correlated with the EORTC sensory subscale (ρ = 0.76). The correlation between the descriptors and EORTC sensory improved (ρ = 0.64 to ρ = 0.71) when the analysis focused on only numbness or tingling. CTCAE grade was more highly correlated with EORTC sensory (ρ = 0.61) and descriptors (ρ = 0.76) compared with EORTC motor (ρ = 0.46). All correlations were statistically significant (p < 0.001). Conclusions: In this mixed cohort of patients, comparison of the various CIPN assessment tools during chemotherapy cycles revealed significant correlations. This suggests the tools are useful in capturing the predominance of sensory symptoms and characterising the sensation of numbness and tingling. Further evaluation of this cohort along with additional studies may provide insight regarding the optimum choice of assessment tool(s).
New conditions identified through a comprehensive geriatric assessment in cancer patients.
Authors: Edwards Beatrice Jara-Almonte , Holmes Holly Michelle , Valladarez Heather , Sun Ming , Khalil Peter , Nguyen Vu , Song Juhee
Published: February 2017

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Background: Chronologic age cannot be used to predict the degree of comorbidity and of functional deterioration of older adults. Assessment of older adults includes health, functional status, nutrition, cognition, socio-economic and mood disorders evaluations. This multidisciplinary assessment is referred to as comprehensive geriatric assessment (CGA). The risk of comorbid conditions increases with age and may result in under diagnosis: in older patients, new symptoms may not be clearly recognized by the patient and may be dismissed by practitioners as manifestations of preexisting conditions. Methods: We conducted a retrospective cohort analysis, of older adult patients (aged 70 years of age and older) evaluated at the Program for Healthy Aging at MD Anderson from January 1, 2013 through December 31, 2014. Assessment was conducted using Katz’ ADLs, Lawton’s IADLs, PHQ-9, the short physical performance battery, the Montreal cognitive assessment, mini nutritional assessment and Charlson co-morbidity index. Medication review and social assessment were also included. Analysis: cross tabulations were performed in SAS 9.4 (SAS Institute INC, Cary, NC) Results: We evaluated 198 patients, (n = 99, 51.6% females). Most common malignancies evaluated included hematologic malignancies (n = 62, 33%), breast cancer (n = 32, 13.2 %), prostate cancer (n = 19, 10 %) and other solid malignancies (n = 85, 43%). The comprehensive geriatric assessment identified a mean of 3 new conditions (range 1-10). The most commonly identified conditions included cognitive impairment and dementia (n = 148, 77%), low bone mass and osteoporosis (n = 67, 34%), malnutrition (n = 65, 34%), frailty (n = 58, 30.2%), and polypharmacy (n = 64, 33%). These conditions are relevant in the management of such patients and could lead to recurring admissions if left unaddressed. Conclusions: A CGA program in a cancer center allows for the identification of medical conditions that directly contribute to clinical outcomes. A CGA allows for the development of a comprehensive plan of care that addresses such issues preventing adverse consequences.
Long-term health outcomes of germ cell tumor survivors.
Authors: Miller Trent James , Einhorn Lawrence H. , Hanna Nasser H. , Champion Victoria , Monahan Patrick , Stump Timothy E. , Brames Mary J. , Case-Eads Somer
Published: February 2017

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Background: Survivors of germ cell tumors (GCT) may face long-term health risks We have previously reported the high incidence of hypogonadism (HG) in survivors of GCT. These patients also may be at risk for other chronic health and psychosocial problems. Methods: Patients treated with chemotherapy (Group 1) or with orchiectomy and/or other surgery or radiotherapy for GCT (Group 2), were 18-50 yrs of age, and not receiving supplemental testosterone at baseline were eligible. Total testosterone was measured at baseline. For patients receiving supplemental testosterone while on study, total testosterone was also measured at 3 and 6 months. Cancer diagnosis and treatment variables were obtained from medical records. Patients completed a validated quality of life (QOL) questionnaire at baseline, 3, and 6 mos. Measures included the Aging Males’ Symptoms (AMS) scale and NIH Patient Reported Outcome Management Information Systems (PROMIS) measures. Results: The rate of HG ( < 300 testosterone) at baseline did not differ between Group 1 and Group 2 (p = 0.45). Compared to non-HG, patients with HG measured at baseline were significantly more likely to have a BMI in the obese ( > 30; 57% vs 19%) range (p < 0.001). Improvements in testosterone during treatment from baseline to follow-up were strongly correlated with improvements in AMS (r = 0.51, p = 0.001) and moderately correlated with improvements in general health (r = 0.32, p = .049). Multivariable models using baseline variables demonstrated that baseline HG was significantly associated with worse baseline quality of life in the areas of general health, sleep quality, and fatigue. BMI in the obesity range was significantly associated with worse general health. Conclusions: Patients who were treated for GCT are at higher risk of HG. This subsequently increases the risk of having a BMI in the obese range, which in turn is associated with worse QOL. Treating HG is associated with improvements in AMS scale.
Recovery of chemotherapy-induced left ventricular dysfunction in cancer survivors.
Authors: Fadol Anecita P. , Banchs Jose , Hassan Saamir , Durand Jean-Bernard , Shelton Valerie , Smith Lisa A. , Fellman Bryan , Zhuang Amy , Yeh Edward T.H.
Published: February 2017

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Background: Chemotherapy-induced left ventricular dysfunction (CILVD) leading to heart failure (HF) is a clinical problem of emerging importance particularly with the 14.5 million cancer survivors who are alive in the United States today, and projected to increase to almost 19 million in 2024. Many of these survivors have received cardiotoxic anticancer agents such as anthracycline and trastuzumab. Research showed that those exposed to anthracyclines are expected to have some degree of cardiac dysfunction 10 to 20 years after treatment and 5% of those patients will develop overt HF. This pilot study investigated whether cancer survivors with CILVD who achieved recovery of cardiac function will maintain their left ventricular ejection fraction (LVEF) if HF medications were discontinued. Methods: We conducted a prospective pilot study on 20 cancer survivors with history of CILVD with recovered cardiac function. HF medications were weaned off in a stepwise process per protocol. Cardiac function was monitored with LVEF measurement per echocardiography and cardiac biomarkers performed at baseline, 2, 4 and 6 months. Patients monitor their heart rate, blood pressure, and symptoms and reported changes based on set parameters. Results: Cancer survivors who maintained their LVEF after discontinuation of HF medications were younger (mean age 47.9 years SD+12.0), 65% female, 55% breast cancer survivors, with no history ofischemic heart disease, hypertension, diabetes mellitus and cardiac dysrhythmias. Chemotherapeutic agents (mean dose) used in the treatment of these patients include doxorubicin (363 mg/m2), epirubicin (527mg /m2), cyclophosphamide (5062 mg), and trastuzumab (6317 mg). There was no significant change from baseline measurements of LVEF and global longitudinal strain (GLS) of 55.1% (± 3.7) GLS of -18.3% (± 2.7) prior to weaning the HF medication to 56% (± 1.6) GLS of -18.2% (± 2.3). after complete withdrawal of HF medications. Conclusions: With the increasing number of young cancer survivors, CILVD may become a frequent clinical issue. Clearly, there is a need to examine the safety of withdrawing HF medications in cancer survivors with CILVD and if lifelong therapy with HF medications is necessary.
Cognitive rehabilitation for brain tumor survivors: A pilot study.
Authors: Richard Nadine M. , Bernstein Lori J. , Mason Warren P. , Laperriere Normand , Chung Caroline , Millar Barbara Ann , Maurice Catherine , Edelstein Kim
Published: February 2017

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Background: Brain tumor survivors often face unique challenges from chronic cognitive deficits such as memory problems or executive dysfunction. Cognitive rehabilitation is a relatively new field. With few well-controlled studies in cancer patients, oncology and supportive care teams lack accessible, reliable tools to address cognitive dysfunction. This pilot study evaluated the feasibility and potential efficacy of two behavioral interventions for brain tumor survivors. Methods: We compared two programs, each with 8 individual treatment sessions and daily homework. Goal Management Training (GMT) is a neuroscience-based integration of mindfulness and strategy training. The Brain Health Workshop (BHW) offers supportive psychoeducation about living with a brain tumor. Using a prospective randomized design, 6 brain tumor patients (with chronic cognitive dysfunction, ≥ 3 months post-radiation or surgery) were enrolled in GMT or BHW and completed a battery of measures at baseline and post-training. Composite scores were calculated by domain, with objective tests of attention, processing speed, memory, and executive functioning, and subjective measures of coping, mood, behavioral regulation and cognitive symptoms. Patient feedback was obtained in post-training qualitative interviews. Results: All patients (Table 1) completed all study activities. Analyses of group differences in composite change scores showed greater improvement in executive functions and greater attainment of pre-training functional goals in the GMT group (p's < .05). The BHW group showed a trend toward greater improvement in mood and behavioral regulation that did not reach statistical significance. Patients in both groups reported satisfaction with their program and continued, frequent (daily to every other day) use of their new knowledge following training. Conclusions: This pilot study demonstrated the feasibility of cognitive rehabilitation for brain tumor survivors between 1 and 8 years post-diagnosis. Results suggest unique benefits of each intervention that will be further explored in a larger clinical trial. [Table: see text]