Catherine E Devine

Phase 2 Trial of Neoadjuvant Axitinib in Patients with Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma

BACKGROUND Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery. OBJECTIVE To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC). DESIGN, SETTING, AND PARTICIPANTS This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible. INTERVENTION Patients received axitinib 5mg for up to 12 wk. Axitinib was continued until 36h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS AND LIMITATIONS A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers. CONCLUSIONS Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC. PATIENT SUMMARY In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use. TRIAL REGISTRATION This clinical trial was registered with clinicaltrials.gov (NCT01263769).

Role of Salvage Targeted Therapy in Differentiated Thyroid Cancer Patients Who Failed First-Line Sorafenib

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.

Imaging of primary and secondary renal lymphoma

OBJECTIVE This article reviews the CT and MRI patterns of primary and secondary renal lymphomas and discusses the role of percutaneous biopsy in diagnosis and management. CONCLUSION Renal lymphoma has a variable imaging spectrum and may mimic renal cell carcinoma. An awareness of the typical and atypical imaging features of both primary and secondary renal lymphomas can help the radiologist to suggest these diagnoses and recommend biopsy when appropriate.

Role of magnetic resonance imaging as an adjunct to clinical staging in cervical carcinoma.

Magnetic resonance imaging depicts the morphological details of the female pelvis and is useful for evaluating both benign and malignant cervical masses. Clinical assessment of the extent of cervical cancer is crucial in determining the optimal treatment strategy, but clinical staging by itself has limitations. Clinical staging, as defined by FIGO (International Federation of Gynecologic Oncology), is based on the findings of physical examination, lesion biopsies, chest radiography, cystoscopy, and renal sonography and can be erroneous, depending on the stage of the disease, by 16% to 65%. The prognosis of cervical cancer is determined not only by stage, but also by nodal status, tumor volume, and depth of invasion, none of which are included in the FIGO guidelines. Magnetic resonance imaging has been described as the most accurate, noninvasive imaging modality in staging cervical carcinoma. This review outlines the magnetic resonance features of normal cervix, primary disease (by stage), and recurrent disease and discusses the role of magnetic resonance imaging in staging and clinical decision making.

PET/CT and cross sectional imaging of gynecologic malignancy

Abstract Gynecologic cancers are a common cause of morbidity and mortality in women of all ages. While many gynecologic cancers are staged clinically using the International Federation of Gynecology and Obstetrics (FIGO) staging system, imaging can be a useful adjunct to clinical staging. Cross sectional imaging techniques such as ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) have been used to detect and follow patients with gynecologic cancer. These imaging modalities can show anatomic detail and morphologic changes in the female genitourinary tract to good advantage. Positron emission tomography (PET) differs in that it shows functional information that is not easily obtained by the other cross sectional imaging techniques. The fusion of PET with CT allows anatomic localization of functional abnormalities in the female genital tract and thereby allows the detection of gross disease in many malignant conditions both within and outside the confines of the female pelvis. The utility and limitations of imaging common gynecologic tumors such as cervical, ovarian and endometrial cancer are discussed with particular emphasis on PET/CT imaging.

Imaging in endometrial carcinoma

Endometrial carcinoma (EC) is the most common gynecologic malignancy in the United States. Prognosis depends on patient age, histological grade, depth of myometrial invasion and/or cervical invasion, and the presence of lymph node metastases. Although EC is staged surgically according to the International Federation of Gynecology and Obstetrics (FIGO) system, preoperative imaging can assist in optimal treatment planning. Several imaging techniques such as transvaginal ultrasonography (TVUS), computed tomography (CT), and magnetic resonance imaging (MRI) have been used as diagnostic tools for preoperative staging of EC. Recently, positron emission tomography (PET), PET/CT, and PET/MRI have also been used in staging these patients. In this article, we review the value of imaging in diagnosis, staging, treatment planning, and detection of recurrent disease in patients with EC.

Radiation Safety With Positron Emission Tomography and Computed Tomography

Combined positron emission tomography and computed tomography (PET/CT) has proven clinical utility, particularly in the diagnosis, staging, and management of cancer. The use of PET/CT has grown substantially in the past few years, with an increasing number of hospitals and imaging centers installing PET/CT systems each year. The combination of 2 procedures, which each imparting a radiation dose and hence the potential for deleterious health effects, creates unique radiation safety issues. This article addresses the radiation safety issues posed by PET/CT with regard to the protection and safety of PET/CT personnel, the public, and adult and pediatric patients.

Variability of inter-observer agreement on feasibility of partial nephrectomy before and after neoadjuvant axitinib for locally advanced renal cell carcinoma (RCC): Independent analysis from a phase II trial

To evaluate how many patients could have undergone partial nephrectomy (PN) rather than radical nephrectomy (RN) before and after neoadjuvant axitinib therapy, as assessed by five independent urological oncologists, and to study the variability of inter‐observer agreement.

Multimodality Imaging of Vulvar Cancer: Staging, Therapeutic Response, and Complications

OBJECTIVE Vulvar carcinoma is a rare malignancy, most commonly seen in elderly women. Survival depends on the lymph node status. Lymph node-negative patients have a 5-year survival of 90%, whereas survival drops to about 50% in patients with positive lymph nodes. The purpose of this article is to familiarize the reader with the revised International Federation of Gynecology and Obstetrics (FIGO) staging of vulvar cancer and incorporate it into daily practice when interpreting cross-sectional imaging studies. CONCLUSION Although vulvar cancer is diagnosed clinically, cross-sectional imaging plays an important complimentary role in staging of the tumor, assessing extent of disease, and selecting operable versus inoperable candidates to ultimately help in decreasing morbidity and increasing survival in these patients.

Primary vaginal cancer: role of MRI in diagnosis, staging and treatment

Primary carcinoma of the vagina is rare, accounting for 1-3% of all gynaecological malignancies. MRI has an increasing role in diagnosis, staging, treatment and assessment of complications in gynaecologic malignancy. In this review, we illustrate the utility of MRI in patients with primary vaginal cancer and highlight key aspects of staging, treatment, recurrence and complications.