Jeannette E. Mares

One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States.

PURPOSE Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology of and prognostic factors for NETs, because a thorough examination of neither had previously been performed. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program registries were searched to identify NET cases from 1973 to 2004. Associated population data were used for incidence and prevalence analyses. Results We identified 35,618 patients with NETs. We observed a significant increase in the reported annual age-adjusted incidence of NETs from 1973 (1.09/100,000) to 2004 (5.25/100,000). Using the SEER 9 registry data, we estimated the 29-year limited-duration prevalence of NETs on January 1, 2004, to be 9,263. Also, the estimated 29-year limited-duration prevalence in the United States on that date was 103,312 cases (35/100,000). The most common primary tumor site varied by race, with the lung being the most common in white patients, and the rectum being the most common in Asian/Pacific Islander, American Indian/Alaskan Native, and African American patients. Additionally, survival duration varied by histologic grade. In multivariate analysis of patients with well-differentiated to moderately differentiated NETs, disease stage, primary tumor site, histologic grade, sex, race, age, and year of diagnosis were predictors of outcome (P < .001). CONCLUSION We observed increased reported incidence of NETs and increased survival durations over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristic of these tumors.

Efficacy of RAD001 (Everolimus) and Octreotide LAR in Advanced Low- to Intermediate-Grade Neuroendocrine Tumors: Results of a Phase II Study

PURPOSE Evaluate the activity of everolimus (RAD001) in combination with octreotide long-acting repeatable (LAR) in patients with advanced low- to intermediate-grade neuroendocrine tumors. METHODS Treatment consisted of RAD001 5 mg/d (30 patients) or 10 mg/d (30 patients) and octreotide LAR 30 mg every 28 days. Thirty carcinoid and 30 islet cell patients were enrolled. RESULTS Intent-to-treat response rate was 20%. Per protocol, there were 13 with partial responses (22%), 42 with stable disease (SD; 70%), and five patients with progressive disease (8%). Overall median progression-free survival (PFS) was 60 weeks. Median PFS for patients with known SD at entry was longer than for those who had progressive disease (74 v 50 weeks; P < .01). Median overall survival has not been reached. One-, 2-, and 3-year survival rates were 83%, 81%, and 78%, respectively. Among 37 patients with elevated chromogranin A, 26 (70%) achieved normalization or more than 50% reduction. Most common toxicity was mild aphthous ulceration. Grade 3/4 toxicities occurring in >or= 10% of patients included hypophosphatemia (11%), fatigue (11%), and diarrhea (11%). Treatment was associated with a dose-dependent rise in lactate dehydrogenase (LDH). Those with lower than 109 U/L rise in LDH at week 4 had shorter PFS (38 v 69 weeks; P = .01). Treatment was also associated with a decrease in proliferation marker Ki-67 among patients who underwent optional paired pre- and post-treatment biopsy (P = .04). CONCLUSION RAD001 at 5 or 10 mg/d was well tolerated in combination with octreotide LAR, with promising antitumor activity. Confirmatory studies are ongoing.

Improving the success rate of gluteal intramuscular injections

Objectives This study aimed to improve the success rate of gluteal intramuscular (IM) injection. Methods The outcomes of 328 intended gluteal IM injections in 115 patients receiving depot octreotide were evaluated using computed tomography performed in routine clinical practice. Patient-, nursing-, and technique-dependent factors were correlated with successful delivery of medication. Techniques associated with successful injection were taught to center nurses. Results At baseline, 52% of injections were successfully delivered (66% men, 36% women; P = 0.001). Factors associated with successful delivery included nurses’ frequency of injections (P = 0.008), landmarks use to select injection site (P < 0.001), quick needle insertion (P < 0.001), and use of nonsyringe hand to compress injection site (P < 0.001). Patient-related factors included male sex (P < 0.001), lower body mass index (P < 0.001), and lower skin-to-muscle depth at injection site (P < 0.001). Techniques associated with successful injections were then taught to center nurses. After instruction, the success rate increased from 52% to 75% (P = 0.001). Importantly, improvements were observed in both men (66%–75%; P = 0.43) and women (38%–75%; P < 0.001). Successful injection was associated with better control of flushing among those with carcinoid syndrome (P = 0.005). Conclusions Intended gluteal IM injections often are given into the subcutaneous space. Education in techniques associated with successful injections improves IM delivery rates.

Metastatic Gastroesophageal Adenocarcinoma Patients Treated with Systemic Therapy Followed by Consolidative Local Therapy: A Nomogram Associated with Long-Term Survivors

Objective: Patients with metastatic gastroesophageal adenocarcinoma (MGEAC) have a poor but heterogeneous clinical course. Some patients have an unusually favorable outcome. We sought to identify clinical variables associated with more favorable outcomes. Methods: Of 246 patients with MGEAC, we identified 64 who received systemic therapy and eventually received local consolidation therapy. Univariate and multivariate Cox regression models were used, and a nomogram was developed. Results: Of these 64 patients, 61% had received consolidation chemoradiation (CRT) with doses of 50-55 Gy and 78% did not undergo surgery. The median follow-up time of survivors was 3.9 years, and the median overall survival (OS) from CRT start was 1.5 years (95% CI, 1.2-2.2). Surgery (as local consolidation) was an independent prognosticator for longer OS in the multivariate analysis (p = 0.02). The 5-year OS rate was 25% (SE = 6%). The contributors to the nomogram were longer duration of systemic therapy before CRT and the type of local therapy. Conclusions: Our data suggest that a subset of patients with MGEAC have an excellent prognosis (OS >5 years). However, these patients need to be identified during their clinical course so that local consolidation (CRT, surgery, or both) may be offered.

Continuation of trastuzumab beyond disease progression in HER2-positive metastatic gastric cancer: the MD Anderson experience

BACKGROUND Despite the wide spread use of trastuzumab in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic gastric cancer patients, its optimal duration of administration beyond first-line disease progression is unknown. In HER2 overexpressing metastatic breast cancer, trastuzumab continuation beyond first-line disease progression has shown improvement in time to progression (TTP) without an increased risk of treatment related toxicity. METHODS HER2-overexpressing metastatic gastric cancer patients were identified from our database between January 2010 and December 2014. We retrospectively reviewed the medical records of 43 patients who received trastuzumab in combination with chemotherapy as first-line and continued trastuzumab beyond disease progression. RESULTS Forty-three cases were identified, 27 males (62.8%), median age of the patients was 58 years. Thirty-five (81.4%) presented with stage 4 as their initial presentation. Eighty one percent had 3+ HER2 overexpression by immunohistochemistry (IHC) and 18% had 2+ HER2 overexpression confirmed by fluorescence in situ hybridization (FISH). Thirteen (52%) were moderately differentiated, 16 (37.1%) were poorly differentiated. The most common sites of metastasis were liver 35 (81.4%) and lung 14 (32.5%). The most commonly used first-line regimen was oxaliplatin, 5-fluorouracil (5-FU), and trastuzumab in 22 (51.1%) patients. Twenty-five (58.1%) patients received irinotecan, 5-FU and trastuzumab in the second-line. Progression-free survival (PFS) was 5 months (95% CI: 4.01-5.99 months). Five patients are still alive and excluded from calculating the median overall survival (OS) which was 11 months (range, 5-53 months) for the remaining 20 subjects of this second-line group. Trastuzumab was not discontinued due to side effects in any of the study population. CONCLUSIONS In conclusion, this retrospective analysis suggests that continuation of trastuzumab beyond disease progression in patients with HER2-overexpressing metastatic gastric cancer is feasible and safe. Randomized studies are warranted.

Utility of endoscopic ultrasound-guided fine-needle aspiration of regional lymph nodes that are proximal to and far from the primary distal esophageal carcinoma

Implications of assessing the proximal and far para-tracheal or sub-carinal nodes (para-tracheal [PTN] or sub-carinal [SCN]) associated with lower primary esophageal carcinomas (ECs) are unclear. To evaluate the value of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) for PTN and SCN, we analyzed results by positron emission tomography (PET) avidity, 4 EUS node malignancy features, and EUS-FNA results in all patients with Siewerts I or II EC. Of 133 patients (PTN, n=102; SCN, n=31) with EUS-FNA, 47 (35%) patients had malignant node, leading to treatment modifications. EUS-FNA diagnosed significantly more patients with malignant nodes (p=0.02) even when PET and EUS features were combined. Among 94 PET-negative and EUS-negative patients, 9 (10%) had malignant EUS-FNA. At a minimum follow-up of 1 year, only 3 (5%) of 62 patients with benign EUS-FNA had evidence of malignancy in the nodal area of prior EUS-FNA. Patients with malignant EUS-FNA independently had a much shorter overall survival (OS) than those with benign EUS-FNA (p<0.001). Our data suggest that a benign EUS-FNA is highly accurate and need not be pursued further. However, malignant EUS-FNA of PTN/SCN was independently prognostic, conferred a shorter OS, and altered the management of 35% of patients.Implications of assessing the proximal and far para-tracheal or sub-carinal nodes (para-tracheal [PTN] or sub-carinal [SCN]) associated with lower primary esophageal carcinomas (ECs) are unclear. To evaluate the value of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) for PTN and SCN, we analyzed results by positron emission tomography (PET) avidity, 4 EUS node malignancy features, and EUS-FNA results in all patients with Siewert’s I or II EC. Of 133 patients (PTN, n=102; SCN, n=31) with EUS-FNA, 47 (35%) patients had malignant node, leading to treatment modifications. EUS-FNA diagnosed significantly more patients with malignant nodes (p=0.02) even when PET and EUS features were combined. Among 94 PET-negative and EUS-negative patients, 9 (10%) had malignant EUS-FNA. At a minimum follow-up of 1 year, only 3 (5%) of 62 patients with benign EUS-FNA had evidence of malignancy in the nodal area of prior EUS-FNA. Patients with malignant EUS-FNA independently had a much shorter overall survival (OS) than those with benign EUS-FNA (p<0.001). Our data suggest that a benign EUS-FNA is highly accurate and need not be pursued further. However, malignant EUS-FNA of PTN/SCN was independently prognostic, conferred a shorter OS, and altered the management of 35% of patients.

Physician Assistants in Oncology

To the Editor: We would like to comment on the efforts of the American Society of Clinical Oncology (ASCO) in identifying the challenges and demands of treating patients with cancer, and in naming physician assistants (PA) and nurse practitioners (NP) as part of the solution.1 At the same time, we are disappointed with two articles published in the May 2007 issue of the Journal of Oncology Practice (JOP), which slight the PA profession. The first article, written by Dr Yu, describes how NPs will have an increased role in the oncology workforce, yet the role of the PA is noticeably omitted.2 In the second article, a biased communication, Dr Cohen expresses his concerns over PAs in oncology.3 We cannot ignore that the section heading for the article by Dr Yu is the “Voice of ASCO.” I can only hope that Dr Yu will follow his current report with a discussion of the role of PAs in oncology. Certainly, an article dedicated to describing the positive impact that PAs can have in caring for patients with cancer is warranted. Or does ASCO not have a voice for PAs? I do not believe this is the case. A liaison to ASCO was created in conjunction with the American Academy of Physician Assistants (AAPA) to represent PAs in oncology at ASCO events. In addition, a new educational symposium made its debut at the ASCO Annual Meeting in 2006. In conjunction with the AAPA, ASCO, and Oncology Nursing Society, the symposium addressed challenges that NPs and PAs face when evaluating patients. Dr Cohens letter deserves attention as well. PAs are educated, motivated, and caring health care providers. The University of Texas M.D. Anderson Cancer Center (MDACC) employs over 160 PAs and relies on their skills, knowledge, and expertise to ensure the highest quality of care. The office of Physician Assistant Programs at MDACC developed a PA journal club, a PA continuing education lecture series, and a postgraduate PA program in oncology. In gastrointestinal medical oncology at MDACC, PAs have had a significant impact on oncology research, publishing original research articles and giving presentations at international oncology meetings.4–10 Other departments at MDACC have equally successful PAs. We admire Dr Cohens engagement with his patients. We also suggest that a PA might allow him to work part-time in his practice or see more patients as a full-time clinician. Dr Erikson et al reported that oncologists who work with NPs or PAs have higher weekly visit rates, and productivity is highest when NPs or PAs are used for advanced activities.1 In addition, PAs provide quality care when working in non–primary care settings. For example, PAs and NPs working in specialty HIV clinics had performance ratings similar to or better than physician ratings for eight quality measures.11 PAs should not diminish the role of the patient-physician relationship in oncology, but rather provide high patient satisfaction, increased revenue, and more forgiving work schedules for their supervising physicians.