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Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P < .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score > 0.6 were independent predictors of CR (all P < .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy.

659 Background: Regular physical activity (PA) is associated with reduced risk of recurrence and mortality in non-metastatic colorectal cancer. Its influence on patients with metastatic colorectal cancer (mCRC) is largely unexplored. Methods: 1231 patients participating in CALGB 80405 (first-line phase III chemotherapy trial for mCRC) completed questionnaires that included self-report on PA at time of chemotherapy initiation and total metabolic equivalent task (MET)-hours/week were determined based on responses. The primary endpoint of the clinical trial and this companion study was overall survival (OS), with progression-free survival (PFS) as a secondary endpoint. To minimize confounding by poor and rapidly declining health, we excluded patients who experienced progression or died within 60 days of activity assessment and adjusted for known prognostic factors, comorbid illness, and weight loss over the previous six months. Results: Compared with patients engaged in less than three MET-hours/week of PA, patients engaged in 18 or more MET-hours/week experienced an adjusted hazard ratio for OS of 0.81 (95% CI 0.67 to 0.98, P for trend 0.03) and for PFS of 0.84 (95% CI 0.71 to 1.00, P for trend 0.03). Greater nonvigorous PA and walking duration were both associated with improved OS ( P for trend 0.01 and 0.04, respectively). Conclusions: In mCRC patients from CALGB 80405, greater total PA was associated with improved PFS and OS, while greater walking duration and non-vigorous PA were associated with reduced risk of all-cause mortality. Support: U10CA180821, U10CA180882. ClinicalTrials.gov ID: NCT00265850 [Table: see text]

348 Background: Neuroendocrine tumor progression is associated with decline in quality of life, both due to tumor and hormone-related symptoms. The Phase III NETTER-1 trial randomized patients with advanced, progressive midgut NETs to receive treatment with 177Lu-DOTATATE (177Lu; Lutathera) versus high-dose (60 mg) Octreotide LAR (Oct). EORTC questionnaires C30 and GINET21 were assessed during the trial in order to determine the impact of treatment on health-related quality of life (HRQoL). Methods: Patients completed EORTC QLQ-30 and QLQ-G.I.NET21 questionnaires at baseline and every 12 weeks thereafter until disease progression. Raw scores were converted to a 100-point scale and individual changes from baseline scores were assessed. Clinically relevant ( ≥ 10 point) deterioration/improvement was considered clinically significant. Results: Clinically and statistically significant improvements in QoL were observed in the 177Lu arm versus the Oct arm at certain time points in key domains of HRQoL including global health status and diarrhea. In mean, global health status improved in 28% of patients on 177Lu arm vs. 15% on Oct, and worsened in 18% of patients on 177Lu vs. 26% on Oct. Diarrhea improved in 39% of patients on 177Lu vs. 23% on Oct, and worsened in 19% of patients on 177Lu vs. 23% on Oct. There was a trend towards improvement in pain that was not statistically significant. Flushing appeared to improve compared to baseline in both arms of the study with no clear advantage to treatment with 177Lu vs. Oct. Conclusions: QoL analysis suggests benefit in important domains associated with 177Lu treatment compared to high-dose octreotide in patients with advanced midgut NETs, and confirms the treatment value of 177Lu on patient QoL, in addition to the meaningful increase in progression-free survival already reported. Clinical trial information: NCT01578239.

The optimal surveillance for patients with resected high-risk melanoma is controversial. Select locoregional or oligometastatic recurrences can be cured with salvage resection. Data on the ability of PET/CT to detect such recurrences are sparse. We evaluated whether surveillance PET/CT in patients with resected stage III–IV melanoma led to detection of clinically occult recurrences amenable to curative-intent salvage treatment. We retrospectively identified 1429 melanoma patients who underwent PET/CT between January 2008 and October 2012 at Mayo Clinic (Rochester, Minnesota). A total of 1130 were excluded because of stage I–II, ocular or mucosal melanoma, incomplete resection, PET/CT not performed for surveillance or performed at a different institution, and records not available. A total of 299 patients were eligible. Overall, 162 (52%) patients developed recurrence [locoregional: 77 (48%), distant: 85 (52%)]. The first recurrence was clinically occult in 98 (60%) and clinically evident in 64 (40%). Clinically evident recurrences were more often superficial (skin, subcutaneous, or nodal) or in the brain, whereas clinically occult recurrences more often visceral. Overall, 90% of all recurrences were detected by 2.8 years. In all, 70% of patients with recurrence underwent curative-intent salvage treatment (locoregional: 94%, distant: 48%), with similar rates for clinically occult versus clinically evident recurrences (66 vs. 75%, P=0.240). Overall survival was superior among those who underwent curative-intent salvage treatment [5.9 vs. 1.2 years; hazard ratio=4.27, 95% confidence interval (CI)=2.68–6.80; P<0.001], despite 79% developing recurrence again. PET/CT had high sensitivity (88%, 95% CI=79.94–93.31%), specificity (90%, 95% CI=88.56–91.56%), and negative predictive value (99%, 95% CI=98.46–99.52%). However, the positive predictive value was only 37% (95% CI=31.32–43.68%). In patients with resected stage III–IV melanoma, surveillance PET/CT detected a large proportion of clinically occult recurrences amenable to curative-intent salvage treatment. Despite a high rate of second relapse, curative-intent salvage treatment was associated with superior overall survival. Even though PET/CT had high sensitivity, specificity, and negative predictive value, positive predictive value was poor, highlighting the need for histologic confirmation of PET/CT-detected abnormalities.

Background: Patients diagnosed with melanoma of the foot have been reported to have a poor prognosis. We reviewed our experience at a tertiary-care medical clinic to determine the disease course in patients diagnosed with melanoma of the foot. Methods: A retrospective review was performed of 38 patients with a diagnosis of primary or locally recurrent melanoma of the foot treated between January, 1988, and July, 2004. The main outcome measures included methods of diagnosis, clinical and histopathologic features, and patterns of recurrence. Results: The mean age at diagnosis was 61 years; most were women (58%) and Caucasian (95%). The average time to diagnosis was 17 months. Initial clinical diagnosis had been considered benign in 12 (32%). The median Breslow thickness was 1.75 mm, T1 lesions were the most common, and acral lentiginous melanoma accounted for 42%. Thirteen patients (34%) had ulcerated lesions. Sentinel lymph node biopsy specimens of 25 patients identified four (16%) with metastatic disease. Surgical complications occurred in 12 patients, usually after skin graft or soft-tissue flap reconstruction. Systemic recurrence developed in six patients, four of whom also had regional recurrence. Conclusions: Most patients were elderly Caucasian women and most presented with early-stage disease, but diagnosis can be difficult and a subgroup presented with thick melanomas. Reconstructive surgical procedures had a high rate of complications; however, overall functional outcomes were good. Stage of cancer at diagnosis was associated with systemic metastases.

The authors compared the relative dosimetric merits of Gamma Knife (GK) and CyberKnife (CK) in 15 patients with 26 brain metastases. All patients were initially treated with the Leksell GK 4C. The same patients were used to generate comparative CK treatment plans. The tissue volume receiving more than 12 Gy (V12), the difference between V12 and tumor volume (V12net), homogeneity index (HI), and gradient indices (GI25, GI50) were calculated. Peripheral dose falloff and three conformity indices were compared. The median tumor volume was 2.50 cm3 (range, 0. 044‐19.9). A median dose of 18 Gy (range, 15‐22) was prescribed. In GK and CK plans, doses were prescribed to the 40‐50% and 77‐92% isodose lines, respectively. Comparing GK to CK, the respective parametric values were: minimum dose ( vs. , ); mean dose ( vs., ); maximum dose ( vs., ); and HI ( vs. , ). The median dosimetric indices (GK vs. CK, with range) were: RTOG_CI, 1.76 (1.12‐4.14) vs. 1.53 (1.16‐2.12), ; CI, 1.76 (1.15‐4.14) vs. 1.55 (1.18‐2.21), ; nCI, 1.76 (1.59‐4.14) vs. 1.57 (1.20‐2.30), ; GI50, 2.91 (2.48‐3.67) vs. 4.90 (3.42‐11.68), ; GI25, 6.58 (4.18‐10.20) vs. 14.85 (8.80‐48.37), . Average volume ratio (AVR) differences favored GK at multiple normalized isodose levels . We concluded that in patients with brain metastases, CK and GK resulted in dosimetrically comparable plans that were nearly equivalent in several metrics, including target coverage and minimum dose within the target. Compared to GK, CK produced more homogenous plans with significantly lower mean and maximum doses, and achieved more conformal plans by RTOG_CI criteria. By GI and AVR analyses, GK plans had sharper peripheral dose falloff in most cases.PACS number: 89.20.‐a

LBA1000 Background: The primary aims were to determine whether adjuvant DD AC→PG will be superior to DD AC→P as well as to TAC in DFS and to compare the relative DFS of TAC and DD AC→P. Secondary endpoints include survival and toxicity. Methods: From Nov 3, 2004 to May 3, 2007, 4894 women were randomized; 1630 to TAC (docetaxel [T] 75 mg/m2, doxorubicin [A] 50 mg/m2, cyclophosphamide [C] 500 mg/m2 q3 wks x 6), 1634 to DD AC→P (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 followed by P 175 mg/m2 q2 wks x 4), and 1630 to DD AC→PG (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 → P 175 mg/m2 + G 2000 mg/m2q2 wks x 4). Primary G-CSF support was required and erythropoiesis-stimulating agents (ESA) were used at investigator discretion. 52% were postmenopausal, 65% had 1 - 3 positive nodes, and 80% had HR+ breast cancer. Log-rank tests were used for pair-wise comparisons of the primary (DFS) and secondary (OS) endpoints among the three treatment arms. Results: With 64 months median follow-up, 5-year DFS in DD AC→PG group was 80.6% compared with 82.2% in DD AC→P group (HR=1.1; p=0.27) and 80.1 % (HR=0.97; p=0.71) in TAC group. 5-year OS was 90.8% in DD AC→PG group as compared with 89.1% (HR=.89; p=0.25) in DD AC→P group and 89.6 % (HR=0.90; p=0.32) in TAC group. HR for DFS and OS of DD AC→P vs. TAC were 0.89 (p=0.14) and 1.01 (p=0.92) respectively. Toxicities for TAC, DD AC→P, DD AC→PG, respectively: febrile neutropenia (Gr 3/4: 9%, 4%, 4% [p<0.001]), sensory neuropathy (Gr 3/4: <1%, 7%, 6% [p<0.001]), diarrhea (Gr 3/4: 8 %, 2%, 2% [p<0.001]). Hgb was <10 in 12%, 26%, 33% with ESA use in 35.2%, 47%, 51.6% and transfusions in 3.7%, 6.3%, 9.4%. Deaths on treatment: N=13, 5, 7 (p=0.2). AML/MDS: N=5, 8, 11. All cycles completed in 91% for TAC and 88% for DD regimens. Conclusions: Addition of G to DD AC→P did not improve outcomes. No significant differences in efficacy endpoints were identified between DD AC→P and TAC, though toxicity profiles differed. Funding: NCI PHS U10-CA-37377, -69974, -12027, -69651 and NCCTG U10-CA25224, with additional funding from Eli Lilly & Company, and Amgen, Inc.