Sloan, Jeff A.

Abstract Background: Traditional adjuvant therapy for oropharyngeal squamous cell carcinoma (OPSCC) consists of 60-66 Gy of radiation therapy (XRT) given in 2 Gy daily fractions along with high dose cisplatin if the patient has high risk factors. Despite the excellent cure rates for HPV+ OPSCC, one in three patients treated with conventional treatment will develop grade >3 long-term sequelae from therapy. There is intense interest in de-intensifying adjuvant therapy for this patient population in order to maximize quality of life while maintaining excellent historical rates of disease control. Methods: MC1273 is a phase II non-randomized trial open at Mayo Clinic Rochester testing a novel course of aggressive therapy de-escalation following surgery for HPV+ OPSCC. The primary endpoint is local/regional control at 2 years while secondary endpoints include toxicity and quality of life (QOL). The eligibility criteria include all patients with p16-positive OPSCC with less than a ten pack-year smoking history who have had a complete surgical resection. Exclusion criteria include positive surgical margins, prior history of malignancy, and history of connective tissue disorders. Patients are divided into two prospective cohorts depending upon risk factors found at surgery. Patients with intermediate risk disease (≥T3, ≥N2, lymphovascular invasion, or perineural invasion) are enrolled in MC1273A while patients with extracapsular extension (ECE) are enrolled in MC1273B. Patients on MC1273A receive 30 Gy of radiation delivered in 1.5 Gy twice-daily fractions over the course of two weeks along with weekly docetaxel (15 mg/m2) given on day 1 and day 8. Patients on MC1273B receive a similar treatment regimen but also have the nodal level with positive ECE concurrently boosted to 36 Gy in 1.8 Gy twice-daily fractions. In addition to standard of care follow-up, patients receive a swallowing assessment with speech therapy immediately before XRT, one month post-XRT, and one year post-XRT. Patients also have QOL assessment consisting of the XeQOLS, Eq-5D, FACT H&N (Vers 4) and Dermatology Life Quality Index assessed at pre-XRT and 3, 12, and 24 months post-XRT. Results: Each cohort of MC1273 is powered to detect a 10% local/regional failure rate with 85% confidence. Each cohort will accrue 35 evaluable patients and 5 additional patients to account for ineligibilities and violations (40 patients total per cohort.) MC1273A began accrual in September 2013. The first five patients were monitored for grade ≥4 acute toxicities before proceeding to open accrual. MC1273B began accrual in May 2014 and has also proceeded to open accrual. Accrual will also begin in Mayo Clinic Scottsdale in the first quarter of 2015. Conclusions: MC1273 is meeting its accrual targets and should finish accrual by 2016. We anticipate that preliminary results for toxicity will be available by 2017 and local/regional data will be available by 2018. Citation Format: Daniel J. Ma, Katharine A. Price, Eric J. Moore, Joaquin J. Garcia, Scott H. Okuno, Daniel L. Price, Jeff A. Sloan, Nathan R. Foster, Robert L. Foote. MC1273: Phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiation in HPV associated oropharynx cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT227. doi:10.1158/1538-7445.AM2015-CT227

Erythropoiesis‐stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy‐associated anemia (CAA). Extended‐interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly (“40K” arm), EA 80,000 U every 3 weeks (“80K”), EA 120,000 U every 3 weeks (“120K” arm), or DA 500 mcg every 3 weeks (“DA”), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb ≥ 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient‐reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA‐approved schedules tested—weekly EA 40,000 U, and every 3 week DA 500 mcg—are reasonable standards for CAA therapy. Am. J. Hematol. 90:877–881, 2015. © 2015 Wiley Periodicals, Inc.

AbstractThis analysis was performed to create a scoring system to estimate the survival of patients with non‐small cell lung cancer (NSCLC). Data from 1274NSCLCpatients were analyzed to create and validate a scoring system. Univariate (UV) and multivariate (MV) Cox models were used to evaluate the prognostic importance of each baseline factor. Prognostic factors that were significant on bothUVandMVanalyses were used to develop the score. These included quality of life, age, performance status, primary tumor diameter, nodal status, distant metastases, and smoking cessation. The score for each factor was determined by dividing the 5‐year survival rate (%) by 10 and summing these scores to form a total score.MVmodels and the score were validated using bootstrapping with 1000 iterations from the original samples. The score for each prognostic factor ranged from 1 to 7 points with higher scores reflective of better survival. Total scores (sum of the scores from each independent prognostic factor) of 32–37 correlated with a 5‐year survival of 8.3% (95%CI = 0–17.1%), 38–43 correlated with a 5‐year survival of 20% (95%CI = 13–27%), 44–47 correlated with a 5‐year survival of 48.3% (95%CI = 41.5–55.2%), 48–49 correlated to a 5‐year survival of 72.1% (95%CI = 65.6–78.6%), and 50–52 correlated to a 5‐year survival of 84.7% (95%CI = 79.6–89.8%). The bootstrap method confirmed the reliability of the score. Prognostic factors significantly associated with survival on bothUVandMVanalyses were used to construct a valid scoring system that can be used to predict survival ofNSCLCpatients. Optimally, this score could be used when counseling patients, and designing future trials.

Background: The burden associated with caregiving has been well documented. Caregivers have multiple responsibilities, and technology may be accessible as a potential burden-alleviating resource. Materials and Methods: We surveyed cancer caregivers regarding current technology use and willingness to use technology for easing burden or distress. Because age has been associated with technology use, responses were compared between geriatric (≥65 years old) and nongeriatric (18–64 years old) caregivers. Results: We had 112 respondents. Based on nonmissing responses, 66% ( n =71) were women, 95% ( n =106) were white, and 84% ( n =91) had post–high school education. Almost all caregivers reported having Internet (105 [94%]) and e-mail (102 [91%]) access. Nongeriatric caregivers indicated more willingness to access Internet-based tools that help caregivers (54 [93%] versus 41 [76%]; p =0.04) and were more frequent users of social media (37 [64%] versus 16 [30%]; p =0.01), smartphones (33 [57%] versus 16 [30%]; p =0.01), and other mobile wireless devices (42 [72%] versus 19 [35%]; p <0.001) than geriatric caregivers. They also more frequently expected technologies to improve their own quality of life ( p =0.009), increase their feelings of being effective as a caregiver ( p =0.02), and save time ( p =0.003). Regardless of age, a majority of caregivers (67 [62%]) endorsed the potential benefit of caregiving technologies in preventing burnout. Conclusions: Most caregivers have high access to and use of technology. Geriatric and nongeriatric caregivers were receptive to technology-based tools to help with their caregiving roles. Although nongeriatric caregivers expected to derive more benefit from such tools, both groups believed that caregiving technologies could reduce burden.

BACKGROUNDPostmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5‐year follow‐up results.METHODSA total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T‐score of <‐2.0 or fracture.RESULTSThe incidence of a 5% decrease in the total lumbar spine bone mineral density at 5 years was 10.2% in the upfront treatment arm versus 41.2% in the delayed treatment arm (P<.0001). A total of 41 patients in the delayed treatment arm were eventually started on ZA. With the exception of increased NCI Common Toxicity Criteria (CTC) grade 1/2 elevated creatinine and fever in the patients treated on the upfront arm and cerebrovascular ischemia among those in the delayed treatment arm, there were no significant differences observed between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront treatment arm (2 vs 8 cumulative cases), although this difference was not found to be statistically significant. Bone fractures occurred in 24 patients in the upfront treatment arm versus 25 patients in the delayed treatment arm.CONCLUSIONSImmediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms. Cancer 2015;121:2537–2543. © 2015 American Cancer Society.

Pulmonary arterial hypertension (PAH) is a chronic, symptomatic, life‐threatening illness; however, it is complex, with variable expression regarding impact on quality of life (QOL). This study investigated attitudes and comfort of physicians regarding palliative care (PC) for patients with PAH and explored potential barriers to PC in PAH. An internet‐based, mixed‐methods survey was distributed to Pulmonary Hypertension Clinicians and Researchers, a professional organization within the Pulmonary Hypertension Association. Only responses from physicians involved in clinical care of patients with PAH were analyzed. Of 355 clinicians/researchers, 79 (22%) returned surveys, including 76 (21%) providers involved in clinical care. Responding physicians were mainly pulmonologists (67%), practiced in university/academic medical centers (89%), had been in practice a mean of 12 ± 7 years, cared for a median of 100 PAH patients per year, and reported a high level of confidence in managing PAH (87%), advanced PAH‐specific pharmacologic interventions (95%), and end‐of‐life care (88%). Smaller proportions were comfortable managing pain (62%) and QOL issues (78%). Most physicians (91%) reported utilizing PC consultation at least once in the prior year, primarily in the setting of end‐of‐life/active dying (59%), hospice referral (46%), or symptomatic dyspnea/impaired QOL (40%). The most frequent reasons for not referring patients to PC included nonapproval by the patient/family (51%) and concern that PC is “giving up hope” (43%). PAH may result in symptoms that impair QOL despite optimal PAH therapy; however, PC awareness and utilization for PAH providers is low. Opportunities may exist to integrate PC into care for PAH patients.

Purpose To evaluate the career plans, professional expectations, and well-being of oncology fellows compared with actual experiences of practicing oncologists. Methods US oncology fellows taking the 2013 Medical Oncology In-Training Examination (MedOnc ITE) were invited to participate in an optional postexamination survey. The survey evaluated fellows' career plans and professional expectations and measured burnout, quality of life (QOL), fatigue, and satisfaction with work-life balance (WLB) using standardized instruments. Fellows' professional expectations and well-being were compared with actual experiences of US oncologists assessed simultaneously. Results Of the 1,637 oncology fellows in the United States, 1,373 (83.9%) took the 2013 MedOnc ITE. Among these, 1,345 (97.9%) completed the postexamination survey. The frequency of burnout among fellows decreased from 43.3% in year 1 to 31.7% in year 2 and 28.1% in year 3 (P < .001). Overall, the rate of burnout among fellows and practicing oncologists was similar (34.1% v 33.7%; P = .86). With respect to other dimensions of well-being, practicing oncologists had lower fatigue (P < .001) and better overall QOL scores (P < .001) than fellows but were less satisfied with WLB (P = .0031) and specialty choice (P < .001). Fellows' expectations regarding future work hours were 5 to 6 hours per week fewer than oncologists' actual reported work hours. Levels of burnout (P = .02) and educational debt (P ≤ .004) were inversely associated with ITE scores. Fellows with greater educational debt were more likely to pursue private practice and less likely to plan an academic career. Conclusion Oncology fellows entering practice trade one set of challenges for another. Unrealized expectations regarding work hours may contribute to future professional dissatisfaction, burnout, and challenges with WLB.