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1.
J Natl Compr Canc Netw ; 22(2D)2024 May 10.
Article in English | MEDLINE | ID: mdl-38729204

ABSTRACT

BACKGROUND: The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center. METHODS: In October 2016, universal HCV screening with HCV antibody (anti-HCV) was initiated for all new outpatients. Universal screening was promoted through widespread provider education, orders in the Epic electronic health records (EHRs), SmartSets, and automated EHR reminders. The effort focused on patients with solid tumors, because universal screening in patients with hematologic malignancies was already standard practice. Primary outcomes were the proportion of patients screened and the proportion of patients with reactive anti-HCV test results linked to HCV care. The secondary outcome was the incidence of HCV-associated hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in patients with a history of other cancers before HCC diagnosis. Epic's Reporting Workbench Business Intelligence tools were used. Statistical significance was defined as P<.05 on chi-square analysis. RESULTS: From April 2016 through April 2023, 56,075 patients with solid tumors were screened for HCV, of whom 1,300 (2.3%) had reactive anti-HCV test results. The proportion of patients screened was 10.1% in the 6 months before study implementation and 34.4% in the last 6 months of the study (P<.001). HCV screening was ordered using SmartSets in 39,332 (45.8%) patients and in response to automated EHR reminders in 10,972 (12.8%) patients. Most patients with reactive anti-HCV test results were linked to care (765/1,300; 59%), most with proven HCV infection were treated (425/562; 76%), and most treated patients achieved sustained virologic response (414/425; 97%). The incidence of HCC-SPMs was 15% in historical controls treated from 2011 to 2017 and 5.7% following implementation of universal screening (P=.0002). CONCLUSIONS: Universal HCV screening can be successfully implemented in cancer hospitals using an EHR-based multipronged approach to eliminate HCV and prevent HCV-associated HCC-SPMs.


Subject(s)
Mass Screening , Tertiary Care Centers , Humans , Male , Mass Screening/methods , Female , Middle Aged , Hepacivirus/isolation & purification , Hepacivirus/immunology , Aged , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/virology , Hepatitis C, Chronic/complications , Hepatitis C/epidemiology , Hepatitis C/diagnosis , Hepatitis C/virology , Hepatitis C Antibodies/blood , Liver Neoplasms/epidemiology , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Incidence , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Electronic Health Records
2.
Article in English | MEDLINE | ID: mdl-38441533

ABSTRACT

CONTEXT: Sporadic medullary thyroid carcinoma (sMTC) rarely occurs in childhood and no studies have specifically focused on this entity. OBJECTIVE: To describe the clinical presentations and long-term outcomes of a large cohort of children and young adults with sMTC compared with hereditary MTC (hMTC). METHODS: Retrospective study of 144 patients diagnosed with MTC between 1961-2019 at an age ≤21 years and evaluated at a tertiary referral center. RESULTS: In contrast to hMTC (n=124/144, 86%), patients with sMTC (n=20/144, 14%) are older (p<0.0001), have larger tumors (p<0.0001), a higher initial stage grouping (p=0.001) and have more structural disease (p=0.0045) and distant metastases (DM) (p=0.00084) at last follow up, but are not more likely to die from MTC (p=0.42). Among 77 patients diagnosed clinically, not by family history (20/20 sMTC and 57/124 hMTC), there was no difference in the initial stage (p=0.27), presence of DM at diagnosis (p=1.0), disease status at last follow-up (p=0.13), overall survival (p=0.57), or disease specific survival (p=0.87). Of the twelve sMTC tumors that underwent somatic testing, eleven (91%) had an identifiable alteration: ten RET gene alterations and one ALK fusion. CONCLUSIONS: sMTC is primarily a RET-driven disease that represents 14% of childhood-onset MTC in this cohort. Pediatric sMTC patients are older, present with clinical disease at a more advanced TNM classification, and have more persistent disease at last follow up compared with hMTC, but these differences disappear when comparing those presenting clinically. Somatic molecular testing should be considered in sMTC patients who would benefit from systemic therapy.

3.
NPJ Digit Med ; 5(1): 67, 2022 Jun 02.
Article in English | MEDLINE | ID: mdl-35654885

ABSTRACT

The strategies of academic medical centers arise from core values and missions that aim to provide unmatched clinical care, patient experience, research, education, and training. These missions drive nearly all activities. They should also drive digital health activities - and particularly now given the rapid adoption of digital health, marking one of the great transformations of healthcare; increasing pressures on health systems to provide more cost-effective care; the pandemic-accelerated funding and rise of well-funded new entrants and technology giants that provide more convenient forms of care; and a more favorable regulatory and reimbursement landscape to incorporate digital health approaches. As academic medical centers emerge from a pandemic-related reactionary digital health posture, where pressures to adopt more digital health technologies mount, a broad digital health realignment that leverages the strengths of such centers is required to accomplish their missions.

4.
Cancer ; 126(16): 3708-3718, 2020 08 15.
Article in English | MEDLINE | ID: mdl-32484922

ABSTRACT

BACKGROUND: Although there are a growing number of survivors of adolescent and young adult (AYA) cancer, to the authors' knowledge the long-term overall survival (OS) patterns for AYA cancer survivors are underreported. The objective of the current study was to assess the long-term survival of AYA cancer survivors and identify factors associated with diminished long-term survival. METHODS: The authors used The University of Texas MD Anderson Cancer Center's tumor registry to identify 5-year survivors of cancer diagnosed as AYAs (ages 15-39 years) between the years 1970 and 2005, and who were alive 5 years after diagnosis. Kaplan-Meier curves were used to estimate OS rates over time, and Cox proportional hazards models were fitted to evaluate the association of covariates with OS. RESULTS: The authors identified 16,728 individuals who were 5-year survivors of cancer and were diagnosed as AYAs with a median follow-up of 20.0 years. The 10-year, 20-year, and 25-year OS rates were 86% (95% confidence interval [95% CI], 85%-86%), 74% (95% CI, 73%-75%), and 68% (95% CI, 67%-68%), respectively, all of which were lower than the age-adjusted estimated survival rates of the general population. Long-term OS improved for AYAs diagnosed between 2000 and 2005 compared with those diagnosed in the prior decades (P < .001). Older age at the time of diagnosis, receipt of radiation, and diagnoses including central nervous system tumors and breast cancer each were associated with diminished long-term survival. CONCLUSIONS: AYA cancer survivors have inferior long-term survival compared with the general population. Studies investigating the prevalence and types of late treatment effects and causes of death among AYA survivors are needed to more accurately identify AYAs who are at highest risk of early or late mortality.


Subject(s)
Age Factors , Cancer Survivors , Neoplasms/epidemiology , Adult , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Neoplasms/pathology , Proportional Hazards Models , Risk Factors , Survival Rate , Young Adult
5.
Head Neck ; 42(6): 1325-1328, 2020 06.
Article in English | MEDLINE | ID: mdl-32437031

ABSTRACT

BACKGROUND: In the face of the COVID-19 pandemic, cancer care has had to adapt rapidly given the Centers for Disease Control and Prevention and the American College of Surgeons (ACS) issuing recommendations to postpone nonurgent surgeries. METHODS: An institutional multidisciplinary group of Head and Neck Surgical Oncology, Surgical Endocrinology, and Medical Endocrinology devised Surgical Triaging Guidelines for Endocrine Surgery during COVID-19, aligned with phases of care published by the ACS. RESULTS: Phases of care with examples of corresponding endocrine cases are outlined. Most cases can be safely postponed with active surveillance, including most differentiated and medullary thyroid cancers. During the most acute phase, all endocrine surgeries are deferred, except thyroid tumors requiring acute airway management. CONCLUSIONS: These guidelines provide context for endocrine surgery within the spectrum of surgical oncology, with the goal of optimal individualized multidisciplinary patient care and the expectation of significant resource diversion to care for patients with COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Endocrine System Diseases/surgery , Patient Selection , Pneumonia, Viral/epidemiology , Triage , Algorithms , COVID-19 , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Endocrine System Diseases/pathology , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Practice Guidelines as Topic , SARS-CoV-2
6.
Pediatr Hematol Oncol ; 37(5): 375-379, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32347770

ABSTRACT

We report a patient who developed chronic myelogenous leukemia (CML) at 12 months of age. She was treated aggressively with stem cell transplant (SCT), interferon, donor lymphocytes and imatinib, with subsequent molecular progression. She received dasatinib, achieving a complete molecular response. Dasatinib was discontinued at 3 years but she had a molecular recurrence. Dasatinib was restarted and continued for 5 additional years with a second major molecular remission (MMR). While on dasatinib therapy she suffered growth failure and was treated with concurrent growth hormone (GH). After discontinuing dasatinib and GH, catch-up growth continues and she remains in MMR. Discontinuation of TKI therapy and the toxicity of long-term TKI therapy is discussed.


Subject(s)
Child Development , Dasatinib/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/therapeutic use , Dasatinib/adverse effects , Female , Humans , Imatinib Mesylate/therapeutic use , Infant , Neoplasm Recurrence, Local , Protein Kinase Inhibitors/adverse effects , Remission Induction , Treatment Outcome , Withholding Treatment
7.
Thyroid ; 30(9): 1288-1296, 2020 09.
Article in English | MEDLINE | ID: mdl-32216548

ABSTRACT

Background: The BRAFV600E mutation is the most common driver mutation in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC). This mutation is considered actionable and, for BRAFV600E-mutated ATC, a BRAF inhibitor (dabrafenib) in combination with an MEK inhibitor (trametinib) is FDA approved. BRAF inhibitors have also shown efficacy in BRAFV600E-mutated PTC. However, as with all targeted therapies, resistance to these drugs eventually develops. It is essential that we understand the mechanisms of resistance to the BRAF inhibitors in thyroid cancer to develop future strategies to effectively treat these patients and improve survival. Patients: Herein, we describe four patients with thyroid cancer treated with selective BRAF inhibitors, who developed a RAS mutation in addition to the BRAFV600E mutation at progression. Results: Patients 1 and 3 acquired a KRASG12V mutation in the progressive tumor, patient 2 acquired a NRASQ61K mutation in a progressive lymph node, and patient 4 acquired NRASG13D mutation on liquid biopsy performed at the time of radiographic disease progression. Conclusion: Similar to the melanoma experience, the emergence of RAS mutations appears to act as a mechanism of resistance to BRAF inhibitors in thyroid cancers.


Subject(s)
Mutation, Missense , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/genetics , Thyroid Cancer, Papillary/drug therapy , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/genetics , Data Collection , Disease Progression , Genes, ras , Humans , Immunotherapy , Liquid Biopsy , Male , Middle Aged , Mutation , Positron Emission Tomography Computed Tomography , Protein Kinase Inhibitors/therapeutic use , Thyroid Cancer, Papillary/mortality , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Neoplasms/mortality , Treatment Outcome
8.
Thyroid ; 29(2): 229-236, 2019 02.
Article in English | MEDLINE | ID: mdl-30759052

ABSTRACT

BACKGROUND: Primary malignant thyroid teratomas are very rare tumors (fewer than 35 previously reported cases in the literature) typically affecting young adult women. While prognosis is poor, there have been some reports of successful treatment regimens. Four cases treated successfully are reported, and a review of the existing literature is provided. PATIENT FINDINGS: Medical records of four patients with histopathologically confirmed malignant thyroid teratomas treated at the University of Texas MD Anderson Cancer Center between 1994 and 2017 were reviewed. The patients were treated with variable treatment regimens consisting of surgical excision with or without aggressive combination chemotherapy (bleomycin, etoposide, and cisplatin; cyclophasphamide, adriamycin, and cisplatin; actinomycin-D, cyclophosphamide, and etoposide; bleomycin, vincristine, and cisplatin; or vincristine, methotrexate, bleomycin, and cisplatin). SUMMARY: All four patients were young women <40 years of age. One patient had thyroid surgery alone, another had surgery with postoperative adjuvant chemotherapy, and two patients underwent neoadjuvant chemotherapy with significant tumor regression prior to definitive thyroid surgery. No patients had postoperative radiation therapy. All patients remained alive and disease free a median of 172 months (range 52-282 months) following completion of therapy. CONCLUSIONS: This case series represents the largest and longest follow-up from a single institution in the literature to date on primary malignant thyroid teratomas. Based on the existing literature and the authors' experience with these four patients, it is suggested that neoadjuvant chemotherapy combined with surgical excision is a promising approach for patients with gross extrathyroidal extension, cervical lymph node metastases, and/or distantly metastatic disease.


Subject(s)
Teratoma/therapy , Thyroid Gland/pathology , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Neoadjuvant Therapy , Pregnancy , Pregnancy Complications, Neoplastic , Prognosis
10.
Ann Surg Oncol ; 25(5): 1395-1402, 2018 May.
Article in English | MEDLINE | ID: mdl-29427212

ABSTRACT

BACKGROUND: No guidelines exist regarding physicians' duty to inform former patients about novel genetic tests that may be medically beneficial. Research on the feasibility and efficacy of disseminating information and patient opinions on this topic is limited. METHODS: Adult patients treated at our institution from 1950 to 2010 for medullary thyroid cancer, pheochromocytoma, or paraganglioma were included if their history suggested being at-risk for a hereditary syndrome but genetic risk assessment would be incomplete by current standards. A questionnaire assessing behaviors and attitudes was mailed 6 weeks after an information letter describing new genetic tests, benefits, and risks was mailed. RESULTS: Ninety-seven of 312 (31.1%) eligible patients with an identified mailing address returned the questionnaire. After receiving the letter, 29.2% patients discussed genetic testing with their doctor, 39.3% considered pursuing genetic testing, and 8.5% underwent testing. Nearly all respondents (97%) indicated that physicians should inform patients about new developments that may improve their or their family's health, and 71% thought patients shared this responsibility. Most patients understood the letter (84%) and were pleased it was sent (84%), although 11% found it upsetting. CONCLUSIONS: Patients believe it is important for physicians to inform them of potentially beneficial developments in genetic testing. However, physician-initiated letters to introduce new information appear inadequate alone in motivating patients to seek additional genetic counseling and testing. Further research is needed regarding optimal methods to notify former patients about new genetic tests and corresponding clinical and ethical implications.


Subject(s)
Adrenal Gland Neoplasms/genetics , Carcinoma, Neuroendocrine/genetics , Communication , Genetic Testing , Paraganglioma/genetics , Pheochromocytoma/genetics , Physician's Role , Thyroid Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Genetic Counseling/psychology , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Motivation , Surveys and Questionnaires
11.
Head Neck ; 39(7): 1291-1295, 2017 07.
Article in English | MEDLINE | ID: mdl-28452157

ABSTRACT

BACKGROUND: Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Several treatment trials are available, but the number of eligible patients to participate is very low because of the rarity and aggressiveness of the disease. METHODS: Facilitating Anaplastic Thyroid Cancer Specialized Treatment (FAST) is a quality improvement project aimed at decreasing time from referral to disposition (scheduling of first appointment) to our institution. After identifying reasons for delays, we created a new process flow specifically for patients with ATC allowing patients to be scheduled immediately. RESULTS: Historical data revealed a mean referral to disposition time for patients with ATC of 8.7 days before our intervention. After the intervention, the mean referral to disposition time was reduced to 0.5 days. Participation in treatment trials for all patients with ATC was 34%. CONCLUSION: Since the implementation of FAST, the access time has decreased and the number of successful referrals for ATC has increased significantly.


Subject(s)
Patient Care Planning/organization & administration , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/pathology , Thyroid Neoplasms/therapy , Academic Medical Centers , Biopsy, Needle , Combined Modality Therapy , Critical Pathways , Disease-Free Survival , Female , Humans , Immunohistochemistry , Interdisciplinary Communication , Male , Quality Improvement , Radiotherapy, Adjuvant , Risk Assessment , Survival Analysis , Thyroid Carcinoma, Anaplastic/mortality , Thyroid Neoplasms/mortality , Thyroidectomy/methods , Thyroidectomy/mortality , Treatment Outcome , United States
12.
J Clin Endocrinol Metab ; 101(12): 4871-4877, 2016 12.
Article in English | MEDLINE | ID: mdl-27662441

ABSTRACT

CONTEXT: Bone metastases (BM) can lead to devastating skeletal-related events (SREs) in cancer patients. Data regarding medullary thyroid carcinoma (MTC) with BM are lacking. OBJECTIVE: We evaluated the natural history of BM and SREs in MTC patients identified by a cancer center tumor registry. SETTING: The study was conducted at a tertiary cancer center. PATIENTS AND MAIN OUTCOME MEASURES: We retrospectively reviewed the charts of MTC patients with BM who received care from 1991 to 2014 to characterize BM and SREs. RESULTS: Of 1008 MTC patients treated, 188 were confirmed to have BM (19%), of whom 89% (168 of 188) had nonosseous distant metastases. Median time from MTC to BM diagnosis was 30.9 months (range 0-533 mo); 25% (45 of 180) had BM identified within 3 months of MTC diagnosis. Median follow-up after detecting BM was 1.6 years (range 0-23.2 y). Most patients (77%) had six or more BM lesions, most often affecting the spine (92%) and pelvis (69%). Many patients (90 of 188, 48%) experienced one or more SREs, most commonly radiotherapy (67 of 90, 74%) followed by pathological fracture (21 of 90, 23%). Only three patients had spinal cord compression. Patients with more than 10 BM lesions were more likely to experience SREs (odds ratio 2.4; P = .007), with no difference in 5-year mortality after MTC diagnosis between patients with (31%) and without SREs (23%) (P = .11). CONCLUSIONS: In this large retrospective series, BM in MTC was multifocal, primarily involving the spine and pelvis, supporting screening these regions for metastases in at-risk patients. SREs were common but spinal cord compression was rare. Antiresorptive therapies in this population should be investigated further with prospective trials.


Subject(s)
Bone Neoplasms/complications , Bone Neoplasms/pathology , Carcinoma, Neuroendocrine/pathology , Registries , Spinal Cord Compression/etiology , Spinal Fractures/etiology , Thyroid Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/epidemiology , Bone Neoplasms/secondary , Carcinoma, Neuroendocrine/epidemiology , Child , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Retrospective Studies , Spinal Cord Compression/epidemiology , Spinal Fractures/epidemiology , Thyroid Neoplasms/epidemiology , Young Adult
13.
Thyroid ; 25(10): 1085-90, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26200040

ABSTRACT

INTRODUCTION: Medullary thyroid cancer (MTC)-related diarrhea can be debilitating, reduces quality of life (QOL), and may be the only indication for initiating systemic therapy. Conventional antidiarrheal drugs are not always helpful and may have side effects. Calcium aluminosilicate antidiarrheal (CASAD), a natural calcium montmorrilonite clay, safely adsorbs toxins and inflammatory proteins associated with diarrhea. It was hypothesized that CASAD would reduce the severity of diarrhea and improve QOL in MTC patients. METHODS: This was a prospective pilot trial (NCT01739634) of MTC patients not on systemic therapy with self-reported diarrhea of three or more bowel movements (BMs) per day for a week or more. The study design included a one-week run-in period followed by one week of CASAD ± a two-week optional continuation period. The primary endpoint was efficacy of one week of CASAD treatment in decreasing the number of BMs per day by ≥20% when compared with the baseline run-in period. Secondary objectives included tolerability and safety and the impact on QOL using the MD Anderson Symptom Inventory-Thyroid questionnaire (MDASI-THY). RESULTS: Ten MTC patients (median age = 52 years, 70% female, 80% white) were enrolled. All had distant metastases, and median calcitonin was 5088 ng/mL (range 1817-42,007 ng/mL). Ninety percent had received prior antidiarrheals, and 40% of these had used two or more drugs, including tincture of opium (30%), loperamide (50%), diphenoxylate/atropine (20%), colestipol (10%), or cholestyramine (10%). Of seven evaluable patients, four (56%) had ≥20% reduction in BMs per day. Six out of seven patients discontinued their prior antidiarrheals. Best response ranged from 7% to 99% reduction in mean BMs/day from baseline. Five out of seven patients considered CASAD a success, and they opted for the two-week continuation period. Improvements in diarrhea and all six interference items assessed by MDASI-THY were noted at weeks 1 and 3. Total interference score was significantly improved at three weeks compared with baseline (p = 0.05). An oral levothyroxine absorption test was performed in one patient; malabsorption of levothyroxine was not observed. Adverse events included flatulence (40%), bloating (10%), heartburn (10%), and constipation (10%). CONCLUSIONS: CASAD is a promising strategy for treatment of MTC-related diarrhea. In this small pilot study, improvements in frequency and quality of diarrhea as well as QOL were noted. Further studies in this population are warranted.


Subject(s)
Aluminum Silicates/therapeutic use , Antidiarrheals/therapeutic use , Carcinoma, Medullary/complications , Diarrhea/drug therapy , Thyroid Neoplasms/complications , Adult , Aged , Clay , Diarrhea/etiology , Female , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Quality of Life , Treatment Outcome
15.
J Clin Endocrinol Metab ; 100(1): E77-81, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25353071

ABSTRACT

CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation. OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial. DESIGN: A retrospective review at MD Anderson Cancer Center. METHODS: The best responses were evaluated using RECIST v1.1. A single radiologist reviewed all images. Adverse events (AEs) were evaluated using CTCAE v.4.0. RESULTS: We identified 17 patients with advanced PTC harboring the BRAF(V600E) mutation who were treated with vemurafenib outside of a clinical trial. Median age at diagnosis was 63 years, and 53% were male. At vemurafenib start, 3 (18%) patients had disease confined to the neck, and 14 (72%) had distant metastases. Tyrosine kinase inhibitors had been previously administered to 4 (24%) patients. Two (12%) patients discontinued vemurafenib because of AEs before restaging. Best response: partial response (PR) in 7/15 (47%) and stable disease (SD) in 8/15(53%) patients. The rate of durable response (PR plus SD ≥ 6 months) was 67%. Median time to treatment failure was 13 months. There was no association between change in thyroglobulin and tumor size. Drug discontinuation, drug interruptions, and dose reductions were needed in 5 (29%), 13 (76%), and 10 (59%) patients, respectively. Most common AEs were fatigue (71%), weight loss (71%), anorexia (65%), arthralgias (59%), hair loss (59%), rash (59%), hand-foot syndrome (53%), calluses (47%), diarrhea (47%), fever (41%), dry mouth (35%), nausea (35%), and verrucous keratosis (35%). Grade ≥ 3 AEs were present in 8 (47%) patients. CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation. Our results are similar to those reported in a phase II clinical trial and support the potential role of vemurafenib in this patient population.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Indoles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Sulfonamides/therapeutic use , Thyroid Neoplasms/drug therapy , Aged , Antineoplastic Agents/adverse effects , Carcinoma/genetics , Carcinoma/pathology , Carcinoma, Papillary , Female , Humans , Indoles/adverse effects , Male , Middle Aged , Off-Label Use , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , Sulfonamides/adverse effects , Thyroid Cancer, Papillary , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Treatment Outcome , Vemurafenib
16.
Endocrinol Metab Clin North Am ; 43(2): 423-42, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24891170

ABSTRACT

Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer, demonstrating variable behavior from indolent disease to highly aggressive, progressive disease. There are distinguishing phenotypic features of sporadic and hereditary MTC. Activation or overexpression of cell surface receptors and up-regulation of intracellular signaling pathways in hereditary and sporadic MTC are involved in the disease pathogenesis. There has been an exponential rise in clinical trials with investigational agents, leading to approval of 2 medications for progressive, advanced MTC. Developments in understanding the pathogenesis of MTC will hopefully lead to more effective and less toxic treatments of this rare but difficult to treat cancer.


Subject(s)
Carcinoma, Medullary/pathology , Thyroid Neoplasms/pathology , Antineoplastic Agents/therapeutic use , Carcinoma, Medullary/drug therapy , Carcinoma, Medullary/metabolism , Humans , Prognosis , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/metabolism
17.
Oncologist ; 19(5): 477-82, 2014 May.
Article in English | MEDLINE | ID: mdl-24733667

ABSTRACT

Sorafenib has proven efficacy in advanced differentiated thyroid cancer (DTC), but many patients must reduce the dose or discontinue treatment because of toxicity. The tolerability and efficacy of lower starting doses of sorafenib for DTC remain largely unstudied. Methods. We retrospectively examined overall survival, time to treatment failure, time to progression, discontinuation rates, and dose-reduction and interruption rates in patients with metastatic DTC treated with first-line sorafenib outside of a clinical trial. Two patient groups were compared; group 1 received the standard starting dose of 800 mg/day, and group 2 received any dose lower than 800 mg/day. Results. We included 75 adult patients, with 51 in group 1 and 24 in group 2. Mean age at diagnosis was 54 years, and 56% were male. The most common histologies included 43% papillary thyroid cancer of the conventional type, 15% papillary thyroid cancer of the follicular variant, and 15% Hürthle cell carcinoma. Time to treatment failure was 10 months (95% confidence interval [CI]: 5.6-14.3) in group 1 and 8 months (95% CI: 3.4-12.5) in group 2 (p = .56). Median overall survival was 56 months (95% CI: 30.6-81.3) in group 1 and 30 months (95% CI: 16.1-43.8) in group 2 (p = .08). Rates of discontinuation due to disease progression were 79% in group 1 and 91% in group 2, and 21% in group 1 and 9% in group 2 (p = .304) stopped treatment because of toxicity. Dose-reduction rates were 59% and 43% (p = .29), and interruption rates were 65% and 67% (p = .908) in group 1 and group 2, respectively. Conclusion. Efficacy and tolerability of sorafenib in treatment-naïve DTC patients does not appear to be negatively influenced by lower starting daily doses.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Thyroid Neoplasms/drug therapy , Adenoma, Oxyphilic , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Carcinoma/mortality , Carcinoma, Papillary , Disease Progression , Disease-Free Survival , Female , Humans , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/adverse effects , Niacinamide/therapeutic use , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/adverse effects , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , Sorafenib , Thyroid Cancer, Papillary , Thyroid Neoplasms/mortality
18.
Thyroid ; 24(7): 1096-106, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24617864

ABSTRACT

BACKGROUND: Age-related risk of medullary thyroid carcinoma (MTC) development in presymptomatic carriers of lower risk germline RET mutations is uncertain; such data may aid counseling patients regarding timing of thyroidectomy. METHODS: From an institutional database and an exhaustive literature review, we identified 679 patients with American Thyroid Association (ATA) level A or B mutations who were identified because of family screening (index cases of MTC were excluded to minimize selection bias). We evaluated age at thyroidectomy or last evaluation if no thyroidectomy, preoperative calcitonin level (elevated or not), the mutated codon, and outcome (MTC vs. no MTC after thyroidectomy or no clinical evidence of MTC if thyroid intact). Data were used to estimate the cumulative prevalence of MTC and/or assess likelihood of MTC stratified by codon. After exclusion of cases with missing data or small representation, 503 patients with mutations in codons 533, 609, 611, 618, 620, 791, and 804 were analyzed. RESULTS: 236 patients had MTC. Cumulative prevalence and median time to MTC varied by codon and within ATA risk levels (p<0.0001). Patients with a codon 620 mutation were 2.8-6.9 times more likely to have MTC than other level B mutation carriers, and 5.1-21.7 times more likely than level A mutation carriers included in our focus population. The youngest median time to MTC was 19 years for codon 620 and the oldest was 56 years for codon 611. Cumulative prevalence of MTC by age 20 was 10% or lower for codons 533, 609, 611, 791, and 804. By age 50, it ranged from 18% for codon 791 to 95% for codon 620. An elevated preoperative calcitonin level strongly predicted MTC on final pathology, though false-negative rates varied by codon (p<0.0001). Positive predictive values ranged from 76% to 100% by codon with an overall positive predictive value of 87% across codons. CONCLUSIONS: This study offers a better understanding of the age-related development of MTC in lower risk RET mutation carriers, provides evidence of further distinctions between lower risk mutations within ATA subgroups, and clarifies the clinical significance of codon 791 mutations. The data support individualized "codon-based" management approaches coupled with clinical data such as calcitonin levels.


Subject(s)
Carcinoma, Medullary/epidemiology , Germ-Line Mutation , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Carcinoma, Medullary/genetics , Carcinoma, Medullary/pathology , Child , Child, Preschool , Databases, Factual , Female , Humans , Infant , Male , Middle Aged , Prevalence , Proto-Oncogene Mas , Risk , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Young Adult
19.
J Clin Endocrinol Metab ; 99(6): 2086-94, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24628550

ABSTRACT

CONTEXT: Sorafenib, a tyrosine kinase inhibitor, is a common first-line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem. OBJECTIVE: The objective of the study was to determine the efficacy of salvage therapy after first-line sorafenib failure. DESIGN: This was a retrospective review at M. D. Anderson Cancer Center from January 2005 to May 2013. PATIENTS: The study included patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). PATIENTS who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS). OUTCOME MEASURES: Progression-free survival, best response, and median OS were measured. RESULTS: Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients receiving first line sorafenib was 37 months; median OS was significantly longer with salvage therapy compared with sorafenib alone (58 vs 28 months, P = .013). In group 2, 17 patients were evaluable for best response, although two patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response in 2 of 15 (13%), stable disease in 10 of 15 (67%), and progressive disease in 3 of 15 (20%) patients. With salvage therapy, partial responses were seen in 7 of 17 (41%) and stable disease in 10 of 17 (59%) patients. Median progression-free survival was 7.4 months with first-line sorafenib and 11.4 months with salvage therapy. Salvage therapy included sunitinib (n = 4), pazopanib (n = 3), cabozantinib (n = 4), lenvatinib (n = 3), and vemurafenib (n = 3). CONCLUSIONS: Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Papillary, Follicular/drug therapy , Molecular Targeted Therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Salvage Therapy/methods , Thyroid Neoplasms/drug therapy , Adult , Aged , Carcinoma, Papillary, Follicular/mortality , Carcinoma, Papillary, Follicular/pathology , Chemotherapy, Adjuvant , Drug Resistance, Neoplasm/drug effects , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Metastasis , Niacinamide/therapeutic use , Retrospective Studies , Sorafenib , Thyroid Neoplasms/mortality , Thyroid Neoplasms/pathology , Treatment Failure
20.
Surg Endosc ; 27(11): 4026-32, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23765427

ABSTRACT

BACKGROUND: For patients with known or suspected adrenocortical carcinoma (ACC), considerable controversy exists over the use of laparoscopic adrenalectomy. The purpose of this study was to assess recurrence and survival patterns in patients with a pathologic diagnosis of ACC treated with laparoscopic versus open adrenalectomy. METHODS: All patients referred to our center with a diagnosis of ACC from April 1, 1993 to May 1, 2012 were reviewed. Three groups of patients were compared: patients referred after laparoscopic resection elsewhere, patients referred after open resection elsewhere, and patients treated primarily at our center (all resected by the open approach). Clinical factors and overall, recurrence-free, and peritoneal recurrence-free survivals were compared between groups. RESULTS: During the study period, 46 patients presented after laparoscopic resection at an outside institution, 210 patients after open resection at an outside institution, and 46 patients were treated at our institution with open resection. Despite a smaller tumor size, patients treated laparoscopically developed peritoneal carcinomatosis more frequently compared to those treated with an open approach (p = 0.006 for number with peritoneal recurrence). When controlling for tumor stage, open-approach patients experienced superior recurrence-free and overall survival. CONCLUSION: Despite typically being performed in patients with smaller tumors, laparoscopic adrenalectomy for ACC is associated with higher rates of recurrence, particularly peritoneal recurrence. For patients with known or suspected ACC, the oncologic benefits of open resection outweigh the short-term benefits of minimally invasive surgery.


Subject(s)
Adrenal Cortex Neoplasms/surgery , Adrenalectomy/adverse effects , Adrenocortical Carcinoma/surgery , Laparoscopy/adverse effects , Neoplasm Recurrence, Local/etiology , Adrenal Cortex Neoplasms/pathology , Adrenocortical Carcinoma/pathology , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Survival Analysis , Treatment Outcome , Young Adult
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