Cancer, diabetes, survival and glycemic control: a large multisite analysis.

Aim: To determine overall survival (OS) and glycemic control in patients with cancer and diabetes. Materials & methods: Patients of our institution with breast, colon, lung, pancreas and prostate cancer were retrospectively reviewed. OS was compared between matched patients with and without diabetes, and changes in glucose value over time were assessed. Results: For 3934 patients each with and without diabetes, adjusted analysis showed no difference in OS according to diabetes status (hazard ratio: 1.07; 95% CI: 0.96-1.20). Mean glucose values decreased over time in patients with and without diabetes (p = 0.01). Conclusion: In this large study of patients with five common cancers, the co-occurrence of diabetes did not affect OS. Cancer did not adversely affect glucose levels.

The aim of this study was to evaluate survival and glucose control in patients with cancer and diabetes at three separate geographic locations in a single health system. From an institutional cancer registry, we identified patients with breast, colon, lung, pancreas and prostate cancers. Patients with and without diabetes were matched by age, sex, cancer type, staging, geographic location and year of cancer diagnosis. In this study, the co-occurrence of diabetes did not affect overall survival. Cancer did not adversely affect glucose levels.

Radiotherapeutic Management of Synchronous Prostate and Rectal Cancers Using Proton Beam Therapy.

Treatment of synchronous prostate and rectal cancers is a rare yet challenging problem with compounded toxicities. We report a case of a 65-year-old man who underwent proton beam therapy (PBT) with concurrent capecitabine and hormonal therapy for his synchronously found prostate (intermediate-risk) and rectal (cT2, N2b, stage IIIB) cancers; he also received low anterior resection. Before PBT, the patient experienced hematochezia. His baseline American Urological Association symptom score was a total of 0, and he was not sexually active. He completed PBT with grade 1 acute toxicities including fatigue, nausea, and increased urinary and bowel frequencies. He also developed mild anemia (10.7), which was resolved. Subsequent surgical pathology showed a pathologic complete response in his rectum. At follow-up of 2.5 years, he remained disease-free on surveillance imaging for both malignancies and reported increased bowel urgency and frequency, minimal urinary leakage when having urgency, and peripheral neuropathy. This case, along with a succinct literature review, demonstrates that PBT can be successful in the definitive treatment of synchronous prostate and rectal cancers with minimal toxicities. Further research is required to evaluate the efficacy and side effect profiles of PBT.

Survival and glycemic control in patients with co-existing squamous cell carcinoma and diabetes mellitus.

AIM: This study examined the impact of diabetes mellitus (DM) on survival in squamous cell carcinoma (SCC) patients, and the impact of SCC on glycemic control. MATERIALS & METHODS: Patients with newly diagnosed SCC with and without DM were matched 1:1 (2007-2017). Overall survival and recurrence-free survival were estimated using the Kaplan-Meier method. Hemoglobin A1c (HbA1c) and glucose level during the year following cancer diagnosis were compared using mixed models. RESULTS: HbA1c decreased over time in DM patients (p = 0.04). The 5-year overall survival was 61% in DM patients, compared with 78% in patients without DM (p = 0.004). CONCLUSION: The presence of co-existing DM adversely impacted survival in patients with SCC. SCC did not affect glycemic control.

Implications of neuroendocrine tumor and diabetes mellitus on patient outcomes and care: a matched case-control study.

AIM: We aimed to determine the impact of diabetes mellitus (DM) on survival of patients with neuroendocrine tumors (NETs) and of NETs on glycemic control. PATIENTS & METHODS: Patients with newly diagnosed NETs with/without DM were matched 1:1 by age, sex and diagnosis year (2005-2017), and survival compared (Kaplan-Meier and Cox proportional hazards). Mixed models compared hemoglobin A1c (HbA1c) and glucose during the year after cancer diagnosis. RESULTS: Three-year overall survival was 72% (95% CI: 60-86%) for DM patients versus 80% (95% CI: 70-92%) for non-DM patients (p = 0.82). Hazard ratio was 1.33 (95% CI: 0.56-3.16; p = 0.51); mean DM HbA1c, 7.3%. CONCLUSION: DM did not adversely affect survival of patients with NET. NET and its treatment did not affect glycemic control.

Panniculitis in a patient with metastatic renal cell carcinoma on a tyrosine kinase inhibitor.

A 71-year-old female was diagnosed with localized renal cell carcinoma in July 2008 with subsequent metastasis in 2012 to the right adrenal gland, lungs, and brain. Due to disease progression, she was started on pazopanib 800 mg daily in October 2012. In November 2016, the patient developed an ill-defined, red, 10 × 15 cm indurated plaque on the left lateral upper thigh with a discrete 3 cm firm tender tumor without ulceration. An incisional biopsy was performed and showed panniculitis with features resembling sclerosing lipogranuloma. Alternative causes including rheumatologic disease and trauma were ruled out. We report the first case of pazopanib-induced panniculitis. Key clinical and histopathological features include tender subcutaneous nodules, exclusion of other causes, and fatty microcysts within a densely sclerotic background on pathology. As targeted therapies are becoming increasingly common in the field of oncology, prompt identification and reporting of adverse reactions is critical for proper management.

Assessing the relationship between institutional cancer and diabetes mortality rates using National Death Index data.

AIM: To evaluate overall survival (OS), glycemic control in cancer patients with and without diabetes mellitus (DM). PATIENTS & METHODS: Patients (2010-2015) with newly diagnosed prostate, breast, lung, colorectal and pancreatic cancers were identified in institutional cancer registry. Data linked to National Death Index for vital status. 5-year OS estimated; glucose and hemoglobin A1c assessed during year postdiagnosis. RESULTS: We identified 1404 patients (non-DM, n = 936; DM, n = 468). DM cohort had 168 deaths (36%); non-DM, 267 (29%). 5-year OS estimated at 58% (95% CI: 53-64%) for DM and 67% (95% CI: 64-71%) for controls; for matched pairs, hazard ratio: 1.35 (95% CI: 1.02-1.79). Cancer did not harm glycemic control. CONCLUSION: OS among cancer patients with DM was lower than without DM.

Management and outcomes of primary vaginal Cancer.

OBJECTIVE: To analyze clinical characteristics and survival of patients with primary vaginal cancer. METHODS: Retrospective analysis of patients with primary squamous, adenocarcinoma and adenosquamous cell carcinoma of the vagina identified from the Mayo Clinic Cancer Registry between 1998 and 2018. RESULTS: A total of 124 patients were identified: stage I, 39 patients; stage II, 44, stage III, 20 and stage IV, 21. Patients with stage III and IV were older as compared to stage I and II. (mean ages 61 vs 67) (p = 0.024). Squamous cell carcinoma made up 71% of tumors. History of other malignancy was present in 24% patients. Median follow-up time was 60 months (range 1-240). Five-year PFS in stage I, II, III and IV was 58.7%, 59.4%, 67.3% and 31.8%, respectively (p = 0.039). Five-year DSS was 84.3%, 73.7%, 78.7% and 26.5% respectively (p < 0.001). Advanced stage, tumor size >4 cm, entire vaginal involvement, and lymph node (LN) metastasis were poor prognosticators in univariate analysis. Primary surgery in stage I/II patients had similar survival outcomes as compared to primary radiation, but post-operative RT rate was 55%. Brachytherapy alone was associated with a high local recurrence (80%) in stage I/II patients. The addition of brachytherapy had improved 5-year PFS and DSS than EBRT alone in patients with stage III/IVA. (p < 0.001). CONCLUSION: Surgery or radiation is effective treatment for vaginal cancer stage I and II. The addition of brachytherapy to external pelvic radiation increases survival in stages III-IV.

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.

Foundation One Genomic Interrogation of Thyroid Cancers in Patients With Metastatic Disease Requiring Systemic Therapy.

CONTEXT: Clinical applications of genomic assessment of thyroid cancers are rapidly evolving. OBJECTIVES, DESIGN, AND SETTING: We studied tumor samples from patients with imminently threatening and rare thyroid cancers to identify genomic alterations that might correlate with outcomes and/or be productively therapeutically targetable. PATIENT CONTEXT: Progressive and metastatic, and/or rare, thyroid cancers were studied, 2012 to 2016, at Mayo Clinic sites. INTERVENTION: The intervention was Foundation One tumor interrogation. MAIN OUTCOME MEASURES: Main outcome measures included genomic alterations, patient characteristics, and overall survival. RESULTS: Samples from 55 patients were evaluated: 20 anaplastic thyroid cancers (ATCs) (36%), 25 radioactive iodine-refractory differentiated thyroid cancers (DTCs)/poorly differentiated thyroid cancers (PDTCs) (45%; 14 papillary thyroid cancer [PTCs], 6 PDTCs, 5 Hürthle cell cancers), 8 medullary thyroid cancers (MTCs) (15%), and 2 others (a spindle epithelial tumor with thymus-like differentiation, and a primary thyroid sarcoma). Overall, 72% of DTCs, 79% of ATCs, and 75% of MTCs were deemed to have potentially productively targetable alterations. The most commonly encountered mutation was of TERT promoter (56% of DTCs, 68% of ATCs)-but this is not presently targetable. Targetable BRAFV600E mutations were found in 40% of DTCs/PDTCs (83% of PTCs) and 32% of ATCs; of MTCs, 75% had targetable RET mutations, and 25% HRAS mutations. Of patient tumors with nonmutated BRAFV600E, 53% of DTC/PDTCs and 69% of ATCs had other potentially productively targetable mutations. Genomic alterations in our series of poor prognosis metastatic DTC/PDTCs also closely resembled those seen in ATC. CONCLUSIONS: Whereas genomic interrogation of favorable prognosis thyroid cancer seems ill advised, potentially productively targetable mutations were demonstrated in the majority of tumors from patients with metastatic thyroid cancers requiring systemic therapy, suggesting a rationale for the selective application of this technology.

Mortality and glycemic control among patients with acute and chronic myeloid leukemia and diabetes: a case-control study.

AIM: We examined the association between diabetes and survival in patients with acute and chronic myeloid leukemia and the association of leukemia with glycemic control. PATIENTS & METHODS: Patients with leukemia with and without diabetes (2007-2015) were retrospectively identified and matched 1:1 (n = 70 per group). Overall survival was estimated by the Kaplan-Meier method. Hemoglobin A1c and glucose levels the year after leukemia diagnosis were compared by mixed models. RESULTS: Among 25 of 70 patients with diabetes, mean hemoglobin A1c during the year after leukemia diagnosis was 6.8%. Kaplan-Meier-estimated 3-year survival was 46% for diabetes patients versus 45% for controls (p = 0.79). CONCLUSION: No associations were found between leukemia, diabetes, survival and glycemic control.

Survival and glycemic control in patients with coexisting lymphoma and diabetes: a case-control analysis.

AIM: We examined the effect of diabetes on survival in patients with lymphoma and the effect of lymphoma on glycemic control. PATIENTS & METHODS: Patients with lymphoma with and without diabetes (2005-2016) were retrospectively identified and matched 1:1. Overall survival and progression-free survival were estimated by the Kaplan-Meier method. Hemoglobin A1c (HbA1c) and glucose levels during the year after cancer diagnosis were compared by mixed models. RESULTS: For patients with diabetes, mean HbA1c during the year after lymphoma diagnosis was 6.7%. Estimated 5-year progression-free survival for patients with versus without diabetes was 63% (95% CI: 53-76%) versus 58% (95% CI: 46-71%) (p = 0.42). CONCLUSION: Lymphoma and its treatment did not affect glycemic control. Diabetes did not decrease lymphoma-specific survival.

Mortality and glycemic control among patients with diabetes mellitus and uterine or ovarian cancer.

AIM: To evaluate associations between survival and glycemic control in age-matched patients with endometrial or ovarian cancer, with/without diabetes mellitus (DM). PATIENTS & METHODS: Patients with newly diagnosed ovarian or endometrial cancer with and without DM were compared. RESULTS: The study included 84 patients with ovarian cancer (28, DM); 96 with endometrial cancer (48 with, 48 without DM). DM patients did not have worse overall or progression-free survival than non-DM patients. Glycemic control was not associated with either cancer. CONCLUSION: There was no association between DM and survival for patients with uterine or ovarian cancer. In addition, there was no association between uterine and ovarian cancer and glycemic control. Additional studies to confirm these observations in larger populations are required.

Glycemic control and survival of patients with coexisting diabetes mellitus and gastric or esophageal cancer.

AIM: To examine effects of diabetes mellitus (DM) on survival in gastric or esophageal (GE) cancer and the cancers' effects on glycemic control. MATERIALS & METHODS: Patients with GE cancer with and without DM were matched 1 to 1 (2006-2016). Characteristics were compared and survival assessed with Kaplan-Meier method and Cox regression. Mixed models compared hemoglobin A1c and glucose over time. RESULTS: Among DM cases, mean hemoglobin A1c was 6.8% in the year after cancer diagnosis. Three-year overall survival was 46% with DM versus 52% without DM (hazard ratio [95% CI]: 1.95 [1.14-3.34]; p = 0.02). CONCLUSION: GE cancer and its treatment did not affect glycemic control. Risks of death and progression were greater for patients with DM than patients without DM.

Survival and glycemic control in patients with coexisting melanoma and diabetes mellitus.

AIM: Given the lack of data in the literature, we examined the impact of diabetes mellitus (DM) on melanoma survival and the impact of melanoma on glycemic control. MATERIALS & METHODS: Patients with melanoma with and without DM were matched 1:1 (2005-2016). Kaplan-Meier analysis was used to estimate overall survival and progression-free survival (PFS). Mixed models compared hemoglobin A1c (HbA1c) and glucose measures over time. RESULTS: Mean HbA1c during the year after cancer diagnosis was 6.7%. The 5-year PFS rate was 89% (95% CI: 81-99%) for patients with DM and 63% (95% CI: 51-79%) for patients without DM (p = 0.02). CONCLUSION: Melanoma did not adversely impact glycemic control. The DM did not adversely impact survival of patients with melanoma, although increased PFS for melanoma was seen in individuals with DM.

Palliative radiotherapy for hepatobiliary obstruction caused by colorectal metastases.

Hyperbilirubinemia in the setting of stent-intolerant biliary obstruction is a challenging problem and can prevent cancer patients from pursuing additional treatments such as further systemic therapies. We report a case of a 75-year-old female who underwent treatment with palliative radiotherapy (RT) for relieving persistent biliary obstruction secondary to liver metastases from colorectal disease, despite prior appropriate stent placement. Prior to RT, the patient's total bilirubin was 14.6 mg/dL, and she experienced fatigue, diarrhea, nausea, vomiting, and severe jaundice. After treatment with 37.5 Gy in 15 once daily fractions, total bilirubin decreased to 3.9 mg/dL, with resolution of previous symptoms including jaundice and pruritus. The patient did not experience any significant treatment-related toxicities. This case, along with a succinct literature review, demonstrates that palliative RT can be successful in relieving biliary obstruction unrelieved by biliary stent. Further research is required to evaluate the efficacy of RT in palliating biliary obstruction for liver metastases in a general population.

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.

Genomic Profiling Reveals Medullary Thyroid Cancer Misdiagnosed as Lung Cancer.

Mutations or other alterations in the RET gene have been implicated in a variety of malignancies - most commonly thyroid, but also chronic myelomonocytic leukemia, acute myeloid leukemia, and lung, breast, pancreatic, and colon cancers. Here we present a case of a gentlemen initially diagnosed with and treated for non-small cell lung adenocarcinoma. Genomic profiling of his tumor specimen revealed a RET point mutation with a known association with medullary thyroid cancer (MTC). Further pathological and molecular diagnostic evaluation confirmed a diagnosis of MTC, leading to a change in treatment from standard chemotherapy for non-small cell lung cancer to targeted therapy against RET and potential implications regarding inherited cancer risk for his offspring. The patient experienced a clinical response to treatment and several months of improved quality of life. This case illustrates the capacity of genomic profiling to uncover molecular drivers of disease and help ensure proper diagnosis and management of cancer.

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.

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.

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.