Perceptual Barriers to Becoming a Plastic Surgeon among Underrepresented Medical Students.

Background: The field of plastic surgery has experienced difficulty increasing diversity among trainees, despite significant efforts. Barriers to recruitment of underrepresented in medicine (URM) students are poorly understood. This study assesses URM students' exposure to plastic surgery, access to mentors and research opportunities, and the importance of diversity in the field. Methods: A survey was designed and distributed to members of the Student National Medical Association over 3 months. Survey data were collected using Qualtrics and descriptive statistics, and logistical regressions were performed using SAS. Results: Of the 136 respondents, 75.0% identified as Black (n = 102/136), and 57.4% (n = 66/115) reported a plastic surgery program at their home institution. Of the total respondents, 97.7% (n = 127/130) were concerned about racial representation in plastic surgery, and 44.9% (n = 53/114) would be more likely to apply if there were better URM representation. Most respondents disagreed that there was local (73.4%, n = 58/79) or national (79.2%, n = 57/72) interest in URM recruitment. Students whose plastic surgery programs had outreach initiatives were more likely to have attending (OR 11.7, P < 0.05) or resident mentors (OR 3.0 P < 0.05) and access to research opportunities (OR 4.3, P < 0.05). Conclusions: URM students feel there is an evident lack of interest in recruiting URM applicants in plastic surgery. Programs with outreach initiatives are more likely to provide URM students access to mentorship and research opportunities, allowing students to make informed decisions about pursuing plastic surgery.

An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer.

Introduction: Multikinase inhibitors have clinical activity in radioactive iodine refractory (RAIR) differentiated thyroid cancers (DTCs) but are not curative; optimal management and salvage therapies remain unclear. This study assessed clinical effects of pazopanib therapy in RAIR-DTC patients with progressive disease, examining in parallel biomarker that might forecast/precede therapeutic response. Methods: Assessment of responses and toxicities and of any association between thyroglobulin (Tg) changes cycle 1 and RECIST (response evaluation criteria in solid tumors) response to pazopanib therapy were prospectively undertaken in Tg antibody negative RAIR-DTC patients. RECIST progressive metastatic disease <6 months preceding enrollment was required. With a sample size of 68 (assuming 23 attaining partial response [PR]), there would be 90% chance of detecting a difference of >30% when the proportion of patients attaining PR whose Tg values decrease by >50% is >50% cycle 1 (one-sided α = 0.10, two sample test of proportions). Mean corpuscular volume (MCV) change or mutational status or pretreatment were also explored as early correlates of eventual RECIST response. Results: From 2009 to 2011, 60 individuals were treated and evaluated; (one additional patient withdrew; another was found ineligible before therapy initiation); 91.7% had previous systemic therapy beyond RAI. Adverse events included one death (thromboembolic) deemed possibly pazopanib associated. Twenty-two confirmed RECIST PRs resulted (36.7%, confidence interval; CI [24.6-50.1]); mean administered 4-week cycles was 10. Among 44 fully accessible patients, the Tg nadir was greater among the 20 attaining PR (median: -86.8%; interquartile range [IQR]: -90.7% to -70.9%) compared with the 28 who did not (median: -69.0%; IQR: -78.1% to -27.7%, Wilcoxon rank-sum test: p = 0.002). However, the difference in the proportion of PRs among those whose Tg fell ≥50% after cycle 1 versus those that did not were not significantly correlated (-23.5% [CI: -55.3 to 8.3]; Fisher's exact test p-value = 0.27). RECIST response was also not correlated with/predicted by early MCV change, receipt of prior therapy, or tumor mutational status. Conclusions: This trial prospectively confirmed pazopanib to have clinical activity and manageable toxicities in patients with progressive RAIR-DTC. Response to pazopanib, however, was not robustly forecast by early associated changes in Tg or MCV, by prior therapy, or by tumor mutational status. ClinicalTrials.gov NCT00625846.

Bacteremia with Staphylococcus pseudintermedius in a 4 month old pediatric oncology patient.

Staphylococcus pseudintermedius colonizes and is a pathogen of dogs and is being increasingly recognized from specimens from humans with various infections. We describe a case of S. pseudintermedius bacteremia in a 4 month old pediatric oncology patient with clear evidence of transmission from the family pet.

Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

Context: Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. Objective: To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. Design: MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Patients: Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Main Outcome Measure: Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Results: Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. Conclusion: MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.

Early and Late Outcomes of Surgical Treatment in Carcinoid Heart Disease.

BACKGROUND: Symptoms and survival of patients with carcinoid syndrome have improved, but development of carcinoid heart disease (CaHD) continues to decrease survival. OBJECTIVES: This study aimed to analyze patient outcomes after valve surgery for CaHD during a 27-year period at 1 institution to determine early and late outcomes and opportunities for improved patient care. METHODS: We retrospectively studied the short-term and long-term outcomes of all consecutive patients with CaHD who underwent valve replacement at our institution between 1985 and 2012. RESULTS: The records of 195 patients with CaHD were analyzed. Pre-operative New York Heart Association class was III or IV in 125 of 178 patients (70%). All had tricuspid valve replacement (159 bioprostheses, 36 mechanical), and 157 underwent a pulmonary valve operation. Other concomitant operations included mitral valve procedure (11%), aortic valve procedure (9%), patent foramen ovale or atrial septal defect closure (23%), cardiac metastasectomies or biopsy (4%), and simultaneous coronary artery bypass (11%). There were 20 perioperative deaths (10%); after 2000, perioperative mortality was 6%. Survival rates (95% confidence intervals) at 1, 5, and 10 years were 69% (63% to 76%), 35% (28% to 43%), and 24% (18% to 32%), respectively. Overall mortality was associated with older age, cytotoxic chemotherapy, and tobacco use; 75% of survivors had symptomatic improvement at follow-up. Presymptomatic valve operation was not associated with late survival benefit. CONCLUSIONS: Operative mortality associated with valve replacement surgery for CaHD has decreased. Symptomatic and survival benefit is noted in most patients when CaHD is managed by an experienced multidisciplinary team.

Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study.

PURPOSE: To assess safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of DEBIO1143, an antagonist of inhibitor apoptosis proteins. METHODS: This first-in-man study in patients with advanced cancer used an accelerated dose titration design. DEBIO1143 was given orally once daily on days 1-5 every 2 or 3 weeks until disease progressed or patients dropped out. The starting dose of 5 mg was escalated by 100% in single patients until related grade 2 toxicity occurred. This triggered expansion to cohorts of three and subsequently six patients and reduction in dose increments to 50%. Maximum tolerated dose (MTD) was exceeded when any two patients within the same cohort experienced dose-limiting toxicity (DLT). On days 1 and 5, PK and PD samples were taken. RESULTS: Thirty-one patients received doses from 5 to 900 mg. Only one DLT was reported at 180 mg. No MTD was found. Most common adverse drug reactions were fatigue (26%), nausea (23%), and vomiting (13%). Average t max and T 1/2 was about 1 and 6 h, respectively. Exposure increased proportionally with doses from 80 to 900 mg, without accumulation over 5 days. Plasma CCL2 increased at 3-6 h postdose and epithelial apoptosis marker M30 on day 5; cIAP-1 levels in PBMCs decreased at all doses >80 mg. Five patients (17%) had stable disease as the best treatment response. CONCLUSION: DEBIO1143 was well tolerated at doses up to 900 mg and elicited PD effects at doses greater 80 mg. Limited antitumor activity may suggest development rather as adjunct treatment.

A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H.

CONTEXT: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -ß; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). OBJECTIVE, DESIGN, SETTING, PATIENTS, INTERVENTION, AND OUTCOME MEASURES: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. RESULTS: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. CONCLUSIONS: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.

Percutaneous image-guided cryoablation of painful metastases involving bone: multicenter trial.

BACKGROUND: This study sought to describe the results of a single-arm multicenter clinical trial using image-guided percutaneous cryoablation for the palliation of painful metastatic tumors involving bone. METHODS: Over a 44-month period, 61 adult patients with 1 or 2 painful bone metastases with a score of 4 or more on a scale of 0 to 10 (≥4/10) worst pain in a 24-hour period who had failed or refused conventional treatment were treated with percutaneous image-guided cryoablation. Patient pain and quality of life was measured using the Brief Pain Inventory prior to treatment, 1 and 4 days after the procedure, weekly for 4 weeks, and every 2 weeks thereafter for a total of 6 months. Patient analgesic use was also recorded at these same follow-up intervals. Complications were monitored. Analysis of the primary endpoint was undertaken via paired comparison procedures. RESULTS: A total of 69 treated tumors ranged in size from 1 to 11 cm. Prior to cryoablation, the mean score for worst pain in a 24-hour period was 7.1/10 with a range of 4/10 to 10/10. At 1, 4, 8, and 24 weeks after treatment, the mean score for worst pain in a 24-hour period decreased to 5.1/10 (P < .0001), 4.0/10 (P < .0001), 3.6/10 (P < .0001), and 1.4/10 (P < .0001), respectively. One of 61 (2%) patients had a major complication with osteomyelitis at the site of ablation. CONCLUSIONS: Percutaneous cryoablation is a safe, effective, and durable method for palliation of pain due to metastatic disease involving bone.

Development of a multidisciplinary, multicampus subspecialty practice in endocrine cancers.

PURPOSE: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. METHODS: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all three Mayo Clinic campuses (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. RESULTS: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased seven times within two years. The number of active therapeutic endocrine malignancies clinical trials also increased from one in 2005 to five in 2009, with all three Mayo campuses participating. CONCLUSION: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

Development of a multidisciplinary, multicampus subspecialty practice in endocrine cancers.

OBJECTIVES: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. METHODS: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all 3 Mayo Clinic campuses (Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. RESULTS: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased 7 times within 2 years. The number of active therapeutic endocrine malignancies clinical trials also increased from 1 in 2005 to 5 in 2009, with all 3 Mayo campuses participating. CONCLUSIONS: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

Hepatic artery embolization for neuroendocrine tumors: postprocedural management and complications.

BACKGROUND: There is scant evidence to guide the management of patients after hepatic artery embolization (HAE). We examined length of stay (LOS), laboratory patterns, medication usage, morbidity, and mortality of patients hospitalized after HAE for metastatic neuroendocrine tumors. METHODS: Data were abstracted retrospectively from electronic medical records on LOS, liver function tests (LFTs), i.v. antibiotics, analgesia, peak temperature, bacteremia, hepatic abscess formation, carcinoid crisis, and metastatic burden on cross-sectional imaging. RESULTS: In 2005-2009, 72 patients underwent 174 HAEs for carcinoid and islet cell tumors. The median LOS was 4 days (range, 1-8 days). There was no correlation between peak LFTs and tumor burden. Declines in LFTs were not uniform before hospital discharge; 25%, 37%, 30%, 53%, and 67% of patients were discharged before their respective aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total and direct bilirubin levels began to decline, with no readmissions for acute hepatic failure. The median i.v. analgesia dose was 60 mg oral morphine equivalents (range, 3-1,961 mg). Pre-HAE i.v. antibiotics were administered in 99% of cases; post-HAE fever occurred in 37% of patients, with no documented bacteremia. One patient developed a hepatic abscess after HAE. There were two carcinoid crises. The single in-hospital death was associated with air in the portal veins. CONCLUSIONS: The duration and intensity of in-hospital care following HAE should be managed on an individual basis. A downward trend in LFTs is not required before discharge. Modest use of i.v. analgesia suggests that many patients could exclusively receive oral analgesics. Given the rarity of serious complications, hospital stays could be shortened, thereby reducing costs and nosocomial risks.

Hepatic arterial infusion and systemic chemotherapy after multiple metastasectomy in patients with colorectal carcinoma metastatic to the liver: a North Central Cancer Treatment Group (NCCTG) phase II study, 92-46-52.

BACKGROUND: Patients with multiple liver metastases from colorectal cancer are at high risk of recurrence after resection. Hepatic artery infusion (HAI) alternating with systemic therapy after surgical resection may improve survival after surgery. METHODS: Patients with liver-only metastases from colorectal cancer amenable to resection/cryoablation were eligible. Previous adjuvant chemotherapy for a completely resected primary tumor was allowed. Alternating courses of HAI and systemic therapy included floxuridine (FUDR) by HAI. Systemic chemotherapy consisted of bolus leucovorin (LV) plus 5-fluorouracil (5-FU). RESULTS: Forty-nine patients had complete resection of their liver metastases, with 44% having more than 4 hepatic metastases and 78% having bilobar disease. Thirty-six patients had HAI FUDR alternating with systemic therapy. Patients received a median of 3.5 cycles (range, 1-4) and 3 cycles (range, 0-6) of therapy with HAI FUDR and systemic therapy, respectively. At the time of final analysis the estimated median disease-free survival and hepatic disease-free survival was 1.2 years (95% confidence interval [CI], 0.9-2.1) and 1.8 years (95% CI, 1.8-not available), respectively. Eleven patients (31%) were alive at this writing. All surviving patients had a minimum of 5.5 years of follow-up. CONCLUSION: This trial of adjuvant chemotherapy in patients who underwent complete resection with unfavorable characteristics demonstrates apparent improvement in outcome compared with historical series treated with surgery alone. However the results of this trial and other randomized trials of HAI do not appear to support its use at this time because of the development of more effective systemic options.

An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma.

BACKGROUND AND RATIONALE: Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. METHODS: The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. RESULTS: Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1-12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. CONCLUSIONS: This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib.

Necrotizing fasciitis caused by methicillin-resistant Staphylococcus pseudintermedius at a previously irradiated site in a dog.

A great Dane dog was presented with a small, superficial wound on the left tarsus that rapidly progressed to a large necrotic area. The dog had undergone radiation therapy in the left tarsal region 33 months previously. Necrotizing fasciitis was diagnosed on histopathological examination, and bacterial culture revealed methicillin-resistant Staphylococcus pseudintermedius.

Fasciite nécrosante causée parStaphylococcus pseudintermediusrésistant à la méthicilline à un site antérieurement irradié chez un chien. Un chien Grand danois a été présenté avec une petite blessure superficielle sur le tarse gauche qui a rapidement progressé pour devenir une grande région nécrotique. Le chien avait subi de la radiothérapie dans la région du tarse gauche 33 mois auparavant. La fasciite nécrosante a été diagnostiquée à l'examen histopathologique et la culture bactérienne a révélé Staphylococcus pseudintermedius résistant à la méthicilline.(Traduit par Isabelle Vallières).

Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients' immediate response to radiofrequency ablation and cryoablation.

OBJECTIVE: The purpose of this article was to compare periprocedural analgesic requirements and hospital length of stay for treatment of patients with painful metastatic tumors involving bone using either percutaneous radiofrequency ablation (RFA) or cryoablation. MATERIALS AND METHODS: A retrospective review was conducted of patients who underwent either imaging-guided cryoablation or imaging-guided RFA for painful metastatic tumors involving bone. The total analgesic usage for 24 hours after the procedure was expressed as a standard morphine-equivalent dose. Analgesic usage at admission served as a baseline for comparison. Total hospital stay was used as an additional measurement of procedure-related morbidity. RESULTS: Fifty-eight patients underwent either cryoablation (n = 36) or RFA (n = 22) for painful metastatic tumors involving bone. Twenty-two primary tumors were treated. The most common treatment site was the pelvis (n = 31). There was no significant difference between the two groups with regard to tumor histologic type (p = 0.52) and location (p = 0.72). The median tumor diameter was 4.4 cm for the cryoablation group and 5.0 cm for the RFA group (p = 0.63). Pretreatment pain scores, measured on a scale of 0 to 10, were not significantly different between the two groups: 6.5 for cryoablation and 6.0 for RFA (p = 0.78). Analgesic use in the 24 hours immediately after the procedure decreased significantly by 24 morphine-equivalent doses after cryoablation, whereas it increased by a median of 22 morphine-equivalent doses after RFA (p = 0.03). Total hospital length of stay for patients undergoing cryoablation was a median of 2.5 days less than that for patients receiving RFA (p = 0.003). CONCLUSION: The use of cryoablation compared with RFA is associated with a greater reduction in analgesic dose and shorter hospital stays after the procedure in the perioperative time frame.

Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study.

BACKGROUND: Chemotherapy has historically proven ineffective in advanced differentiated thyroid cancers, but the realisation that various tyrosine kinases are activated in the disease suggested a potential therapeutic role for tyrosine-kinase inhibitors. We investigated the safety and efficacy of pazopanib. METHODS: This phase 2 trial was done from Feb 22, 2008, to Jan 31, 2009, in patients with metastatic, rapidly progressive, radioiodine-refractory differentiated thyroid cancers. Each patient received 800 mg continuous pazopanib daily in 4-week cycles until disease progression, drug intolerance, or both occurred. Up to two previous therapies were allowed, and measurable disease with radiographic progression in the 6-month period before enrolment was a requirement for inclusion. The primary endpoint was any tumour response, according to the Response Evaluation Criteria in Solid Tumors 1.0. This study is registered with ClinicalTrials.gov, number NCT00625846. FINDINGS: 39 patients were enrolled. One patient had received no previous radioiodine therapy and another withdrew consent before treatment. Clinical outcomes could, therefore, be assessed in 37 patients (19 [51%] men, median age 63 years). The study is closed to accrual of new patients, but several enrolled patients are still being treated. Patients received a median of 12 cycles (range 1 to >23, total >383). Confirmed partial responses were recorded in 18 patients (response rate 49%, 95% CI 35-68), with likelihood of response lasting longer than 1 year calculated to be 66%. Maximum concentration of pazopanib in plasma during cycle one was significantly correlated with radiographic response (r=-0·40, p=0·021). 16 (43%) patients required dose reductions owing to adverse events, the most frequent of which (any grade) were fatigue (29 patients), skin and hair hypopigmentation (28), diarrhoea (27), and nausea (27). Two patients who died during treatment had pre-existing contributory disorders. INTERPRETATION: Pazopanib seems to represent a promising therapeutic option for patients with advanced differentiated thyroid cancers. The correlation of the patient's response and pazopanib concentration during the first cycle might indicate that treatment can be individualised to achieve optimum outcomes. Assessment of pazopanib in an expanded cohort of patients with differentiated thyroid cancer, as well as in cohorts of patients with medullary and anaplastic thyroid cancers, is presently being done. FUNDING: National Cancer Institute, supported in part by NCI CA15083 and CM62205.

Regenerative therapy after cancer: what are the risks?

There is often a pressing need for reconstruction after cancer surgery. Regenerative therapy holds the promise of more natural and esthetic functional tissue. In the case of breast reconstruction postmastectomy, volume retention problems associated with autologous fat transfer could be ameliorated by augmentation with cells capable mediating rapid vascularization of the graft. Intentional placement of regenerating tissue at the site of tumor resection raises questions concerning the possibility of promoting cancer recurrence. Here we review coculture and animal models of tumor/mesenchymal stem cell interactions under regenerating conditions. Available evidence from case reports, cell lines, and clinical isolates favors the interpretation that regenerating tissue promotes the growth of active, high-grade tumor. In contrast, dormant cancer cells do not appear to be activated by the complex signals accompanying wound healing and tissue regeneration, suggesting that engineered tissue reconstruction should be deferred until cancer remission has been firmly established.

Molecular markers for novel therapies in neuroendocrine (carcinoid) tumors.

Neuroendocrine (carcinoid) tumors (NETs) are endocrine neoplasms occurring most frequently in gastrointestinal and bronchopulmonary (BP) systems. The majority of patients present with advanced disease for which few treatment options exist. We assessed 104 NETs (74 cases) for biomarkers targeted by anticancer drugs under development for other forms of cancer. Activating mutations were assessed in epidermal growth factor receptor (EGFR), stem cell factor receptor (KIT), and platelet-derived growth factor receptor alpha (PDGFRA), as well as non-response mutations in KRAS. Copy number of EGFR and HER-2/neu was quantified with fluorescence in situ hybridization. Immunohistochemical analyses were performed for EGFR, KIT, PDGFRA, somatostatin receptor subtypes 2A and 5 (SSTR5), vascular endothelial growth factor receptor 1, mammalian target of rapamycin (mTOR), insulin-like growth factor 1 receptor (IGF1R), heat shock protein 90 (Hsp90), and transforming growth factor-beta receptor 1 (TGFBR1). NETs lacked HER2-overexpression predictive of anti-HER2 response and KIT and PDGFRA activating mutations indicative of imatinib sensitivity. High EGFR aneusomy (20% of all cases) and elevated EGFR copy number (39%) were found, but few KRAS mutations associated with non-response to anti-EGFR therapy (3%). Hsp90, TGFBR1, IGF1R, and SSTR5 exhibited highest levels of immunohistochemical staining in the largest percents of tumors. In subsequent in vitro studies, anticancer drug 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) (targeting Hsp90) inhibited proliferation of BP NET lines NCI-H727, NCI-H720, and NCI-H835 with IC(50) values of 70.4, 310, and 788 nM respectively; BMS-754807 (targeting IGF1R/IR) inhibited growth with IC(50) values of 428 nM, 2.8 microM, and 1 microM. At growth-inhibiting concentrations, 17-AAG (24 h) induced loss of EGFR and IGF1R in the IGF1R-expressing NCI-H727 line, and BMS-754807 (24 h) inhibited constitutive IGF1R autophosphorylation. Our results support further research into Hsp90, IGF1R, and EGFR as targets for developing new anticancer therapeutics for some NETs.

Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and stomach: a pooled analysis of eight consecutive North Central Cancer Treatment Group (NCCTG) trials.

Whether elderly patients with metastatic esophageal, gastroesophageal, and gastric cancer do as well with chemotherapy as their younger counterparts was investigated in this pooled analysis. In total, 367 patients from 8 consecutive, first-line trials were included: i) etoposide + cisplatin; ii) 5-fluorourucil + leucovorin; iii) 5-fluorouracil + levamisole; iv) irinotecan; v) docetaxel + irinotecan; vi) oxaliplatin + capecitabine; vii) docetaxel + capecitabine; and viii) bortezomib + paclitaxel + carboplatin. One hundred and fifty-four (42%) patients were > or =65 years old (range: 65-86), and 213 younger (range: 20-64). Elderly patients had worse performance scores (2-3): 19 vs. 8% (p<0.0001). Rates of grade 3+ adverse events across all chemotherapy cycles in univariate and multivariate analyses (adjusted for gender, performance score, and stratified by individual study) were higher among elderly patients. Rates of neutropenia, fatigue, infection, and stomatitis in elderly vs. younger patients were 31 vs. 29% (p=0.02 by multivariate analyses); 15 vs. 5% (p=0.01); 9 vs. 4% (p=0.03); 6 vs. 1% (p=0.04). In contrast, duration of chemotherapy, overall survival, and progression-free survival were comparable. Although age should not preclude trial entry, these adverse event rates suggest a need to develop more tolerable regimens for older patients with these malignancies.

If you hold it off-hours, will they come? Results from a feasibility project intended to stimulate interest in the physician-investigator career path among medical oncology trainees.

BACKGROUND: An "endangered species," the physician-scientist faces challenges in oncology. The authors thus implemented a series of voluntary off-hours sessions on academic development for their trainees. METHODS: Numerous workday interruptions among trainees led the authors to conclude that off-hours sessions would be preferable. Thus, this feasibility project was conducted. All 34 trainees were invited to a session and were surveyed thereafter. An attendance rate of >or=34% was to be a "success." RESULTS: Seventy percent of trainees attended, and over 90% said they would do so again. Write-in comments were mostly favorable. CONCLUSIONS: Off-hours sessions to discuss academic career development are feasible among medical oncology trainees.