Nina J. Karlin

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 -β; 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.

Cancer with diabetes: prevalence, metabolic control, and survival in an academic oncology practice.

OBJECTIVE To determine the prevalence of diabetes mellitus, glycemic control, and impact of diabetes on overall survival in an academic oncology practice. METHODS Data on cancer patients (1999 to 2008) were retrieved from the institutional cancer registry and linked to electronic files to obtain diabetes status and hemoglobin A1c (A1C) values within the first 6 months of cancer diagnosis. Overall survival by cancer type with and without diabetes was compared using Cox regression. RESULTS Excluding skin and hematologic malignancies, 15,951 cancer cases were identified. Overall diabetes prevalence was 6.8% (n = 1,090), declining over time (P<0.001). Diabetes was common among patients with pancreatic (9.8% [61 of 624]), colorectal (7.7% [89 of 1,151]), or bladder cancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70 versus 66 years; P<0.001) and more likely to be male (66.3% [723 of 1,090] versus 60.2% [8,949 of 14,858]; P<0.001). The mean A1C among diabetic cancer patients was 6.8% and did not differ across cancer types (P = 0.80). Only 58.6% (331 of 565) of diabetic cancer patients had all A1C <7.0% during the first 6 months following cancer diagnosis. Pancreatic cancer patients with coexisting diabetes had better overall survival than pancreatic cancer patients without diabetes (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; P<0.001). Conversely, diabetic prostate cancer patients had worse overall survival than prostate cancer patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to 1.76; P = 0.02). CONCLUSION In this academic oncology practice, diabetes was common, glycemic control often was suboptimal, and survival varied by cancer type. Additional study is needed to optimize glucose management and investigate mechanisms underlying age, sex, and survival differences.

Asian-variant intravascular lymphoma in the African race

Intravascular Large B-cell lymphoma (IVLBCL) is an exceptionally rare form of non-Hodgkin lymphoma (NHL) distinguished by the preferential growth of neoplastic cells within blood vessel lumen. Challenging to detect and deemed disseminated at diagnosis, this condition is characterized by a highly aggressive, inconspicuous course with a high mortality rate. We describe the case of a 48 year-old African-American female presenting with a two month history of low-grade fevers and malaise. Laboratory data was notable for anemia, thrombocytopenia, elevated liver function tests, and hematuria. An extensive work-up for infectious, rheumatologic and malignant causes was negative. Her symptoms progressed and within two weeks, she was admitted for disseminated intravascular coagulation (DIC). Her course was complicated by diffuse pulmonary hemorrhage and ultimately, care was withdrawn. Autopsy identified widespread CD-20 positive intravascular large B-cell lymphoma with significant hepatosplenic involvement, characteristic of the Asian variant IVLBCL. This case uniquely highlights development of the Asian variant IVLBVL in a previously undescribed race. Identified by its intraluminal vascular growth pattern, IVLBCL generally spares lymphatic channels. Diagnosis and differentiation of this condition from other hematological malignancies via skin, visceral and bone marrow biopsy is imperative as anthracycline-containing chemotherapies may significantly improve clinical outcomes. This article outlines the common presentation, natural course, and treatment options of IVLBCL, along with the histopathology, immunohistochemistry, and chromosomal aberrations common to this condition.

CO-EXISTING PROSTATE CANCER AND DIABETES MELLITUS: IMPLICATIONS FOR PATIENT OUTCOMES AND CARE

OBJECTIVE To investigate how diabetes mellitus (DM) impacts short-term overall survival (OS) for patients with prostate cancer and to examine how prostate cancer impacts glycemic control in DM. METHODS Patients with DM and prostate cancer newly diagnosed from 2007 to 2014 were identified from the institutional cancer registry and matched to patients with prostate cancer but no DM according to age and year of prostate cancer diagnosis. RESULTS The study included 276 cases and 276 controls; the mean age was 72 years, most (93%) were white, the most common Gleason score (52%) was 7, and the majority (56%) were tumor stage II. Patients with DM had a higher mean body mass index (P = .03). Alcohol use and performance status differed by group (P<.001), but the 2 groups otherwise were not significantly different. Among those with DM, the mean hemoglobin A1c (HbA1c) was 6.7%. In Kaplan-Meier survival analysis (median follow-up time, 43.7 months), the 5-year OS rates were estimated at 88% and 93% for patients with and without DM, respectively (hazard ratio, 1.64; 95% confidence interval, 0.77-3.46; P = .20). Mean glucose among patients with DM was significantly higher (P<.001) compared with non-DM patients, but mean HbA1c and glucose values did not change significantly over 1 year (P≥.13). CONCLUSION DM did not adversely impact survival in patients with prostate cancer. In addition, prostate cancer and its treatment did not affect glycemic control. Patients and their providers can be reassured that the concurrent diagnoses do not adversely interact to worsen short-term outcomes. ABBREVIATIONS DM = diabetes mellitus; HbA1c = hemoglobin A1c; OS = overall survival.

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.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.

Mayo clinic cancer center experience of metastatic extramammary Paget disease 1998-2012

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy. The most common presentation of EMPD is the vulva followed by perianal involvement. Most cases are localized to the dermis with treatment focused on surgery, topical treatment or radiotherapy. Recurrence is frequent despite therapies utilized. Metastatic extramammary Paget disease is uncommon and, as such, standard treatment guidelines do not exist. This study sought to evaluate the treatment regimens and outcomes of patients treated at a Mayo Clinic Center from 1998-2012. Cancer registry inquiry revealed 261 patients with report advanced Paget disease during these years. Ten cases of metastatic EPMD were identified with sufficient documentation for review. This review reveals support for utilizing localized radiation therapy for bulky disease sequentially with systemic chemotherapy consisting of carboplatin and paclitaxel or irinotecan. Further studies are necessary to define the optimal treatment regimen.

Patient outcomes from lung cancer and diabetes mellitus: a matched case–control study

Aim: This case–control study examined the impact of diabetes mellitus (DM) on survival in lung cancer patients and lung cancer on glycemic control in DM. Materials & methods: Patients with a new lung cancer diagnosis and DM (n = 124) were matched to 124 lung cancer patients without DM. Laboratory results and DM and cancer therapies were obtained from electronic records. Results: Five-year overall survival for lung cancer patients with and without DM was 20 versus 29% (p = .12). Glycemic control among DM patients did not change significantly with time. Conclusion: DM does not cause adverse impact on lung cancer survival. Lung cancer does not affect glycemic control.

Survival and glycemic control outcomes among patients with coexisting pancreatic cancer and diabetes mellitus

Aim: We aimed to determine the effect of diabetes mellitus (DM) on survival in pancreatic cancer and effects of pancreatic cancer on glycemic control in DM. Materials & methods: Patients with pancreatic cancer from 2007 to 2015, with and without DM, were matched 1:1. We compared characteristics between the groups and assessed 2-year survival with Kaplan–Meier analysis. Results: In patients with DM, hemoglobin A1c decreased significantly over time (p = 0.01). In survival analysis, 2-year overall survival estimates were 15% (95% CI: 8–24%) for DM patients versus 26% (95% CI: 17–36%) for non-DM patients (p = 0.55). The hazard ratio for matched pairs was 1.15 (95% CI: 0.75–1.77; p = 0.51). Conclusion: DM did not decrease survival in pancreatic cancer. Pancreatic cancer did not affect glycemic control.

Survival and glycemic control in patients with colorectal cancer and diabetes mellitus

Aim: The impact of diabetes mellitus (DM) on survival in patients with colorectal cancer and the impact of colorectal cancer on glycemic control were examined. Materials & methods: Patients with colorectal cancer with and without DM were matched 1:1 (2007–2015). Characteristics were compared between the two groups and survival assessed with the Kaplan–Meier method. Mixed models compared hemoglobin A1c and glucose levels over time. Results: In both groups, glucose values decreased during the year following cancer diagnosis (p < 0.001). 5-year overall survival was 56% (95% CI: 42–68%) for DM patients versus 57% (95% CI: 43–69%) for non-DM patients (p = 0.62). Conclusion: DM did not adversely impact survival of patients with colorectal cancer. Colorectal cancer did not affect glycemic control.

Leptomeningeal Carcinomatosis in Colorectal Cancer: The Mayo Clinic Experience

Background Leptomeningeal metastasis (LM) is an uncommon form of metastatic disease in many cancers. There remains a paucity of literature with regard to the course and management of LM in colorectal cancers (CRCs). The aim of this study was to estimate the incidence of LM in patients with CRC seen at our institution over a 15‐year period, and to describe the clinical course and outcome of these cases. Methods LM in CRC primary cases between 2000 and 2014 were identified in the Mayo Clinic databases. The charts were retrospectively reviewed. Results Of 17,095 CRC primaries, we identified 10 patients with LM (0.058%) in this 15‐year period. Nine cases were included in the analysis. Four had metastatic disease at the time of their initial CRC diagnosis. Median overall survival after CRC diagnosis was 25.7 months (range, 4.7‐74.8 months). Median time to diagnosis of LM after CRC diagnosis was 25.3 months (range, 0‐68.1 months). All patients had magnetic resonance imaging findings consistent with LM: 3 patients with spinal LM, 5 patients with intracranial LM, and 1 with both. Neurologic symptoms correlated with site of the lesions, with headache, cranial nerve palsy, lower extremity weakness, and gait disturbance among the most frequently reported. However, not all patients had neurologic findings, with LM lesions found incidentally in 2 cases. Seven patients (78%) had palliative radiotherapy for LM. Three patients continued to receive systemic chemotherapy after diagnosis of LM. Median survival after LM diagnosis was 7 weeks (range, 2‐39 weeks). Conclusions LM is an exceedingly rare development in the natural course of CRC. It confers a poor prognosis with limited treatment options. At our institution, most patients had their disease addressed by palliative means, with many receiving radiotherapy to control their neurologic symptoms. Based on our series, supportive care remains a sensible approach to the management of LM in CRC. Micro‐Abstract Leptomeningeal carcinomatosis is an uncommon metastatic progression of colorectal cancer. A database search of 17,095 primary colorectal cancers in a 15‐year period returned 10 cases of leptomeningeal metastasis in these patients. Our series describes their disease course and outcomes. Leptomeningeal carcinomatosis confers a poor prognosis, with most patients receiving palliative therapies after the diagnosis was made.