Pathology and genetics of tumors of soft tissue and bone

Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.

Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for ana...

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Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

A preliminary study: The sequential use of the risk malignancy index and contrast-enhanced ultrasonography in differential diagnosis of adnexal masses.

To be most effective anticancer drugs must penetrate tissue efficiently, reaching all the cancer cells that comprise the target population in a concentration sufficient to exert a therapeutic effect. Most research into the resistance of cancers to chemotherapy has concentrated on molecular mechanisms of resistance, whereas the role of limited drug distribution within tumours has been neglected. We summarize the evidence that indicates that the distribution of many anticancer drugs in tumour tissue is incomplete, and we suggest strategies that might be used either to improve drug penetration through tumour tissue or to select compounds based on their abilities to penetrate tissue, thereby increasing the therapeutic index.

Drug penetration in solid tumours

Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.

A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

Context: There are few large series of patients with ectopic, nonpituitary, corticotropin (ACTH) secretion (EAS). Objective: The objective of this study was to analyze the clinical, biochemical, and radiological features, management, and treatment outcome of patients with EAS. Design: This was a retrospective case-record study. Setting: The setting for this study was a tertiary referral hospital center. Patients: Forty patients with EAS were studied. Main Outcome Measures: Clinical, biochemical, and radiological features and response to therapy and survival were measured. Results: The median follow-up was 5 yr (range, 2–30 yr). None of the dynamic tests achieved 100% accuracy, but bilateral inferior petrosal sinus sampling showed an absent central gradient in all but one case (one of 12). Imaging correctly identified the lesion at first investigation in 65% of cases. Bronchial carcinoid tumors were the most common cause of EAS (n = 12; 30%), followed by other neuroendocrine tumors (n = 13, 32.5%). In 12.5...

The Ectopic Adrenocorticotropin Syndrome: Clinical Features, Diagnosis, Management, and Long-Term Follow-Up

Purpose Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node–specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. Methods Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients. Results Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 o...

Diagnostic Performance of Nanoparticle-Enhanced Magnetic Resonance Imaging in the Diagnosis of Lymph Node Metastases in Patients With Endometrial and Cervical Cancer

OBJECTIVE: To investigate visceral fat distribution in patients with schizophrenia. DESIGN: Cross sectional study using CT scanning in patients with drug-naive and drug-free schizophrenia. SUBJECTS: Fifteen (13 men and two women) subjects with schizophrenia (mean age 33.7 y; mean body mass index (BMI)=26.7 kg/m2), and 15 age- and sex-matched controls (mean age 30.5 y; mean BMI=22.8 kg/2). MEASUREMENTS: Various fatness and fat distribution parameters (by CT scanning and anthropometry) and 16:00 h plasma cortisol. RESULTS: In comparison to controls, patients with schizophrenia had central obesity and had significantly higher levels of plasma cortisol. Furthermore, previous neuroleptic exposure did not appear to influence these findings as both drug-naive and drug-free patients had equally high levels of visceral fat deposition. CONCLUSION: Central obesity is a well recognized risk factor in developing certain general medical conditions. This study shows that patients with schizophrenia have increased intra-abdominal fat which may provide one explanation for why they die prematurely.

Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia.

https://www.rcpjournals.org/content/clinmedicine/8/4/451.full.pdf

Rodney H. Reznek

Papers

A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

The Ectopic Adrenocorticotropin Syndrome: Clinical Features, Diagnosis, Management, and Long-Term Follow-Up

Diagnostic Performance of Nanoparticle-Enhanced Magnetic Resonance Imaging in the Diagnosis of Lymph Node Metastases in Patients With Endometrial and Cervical Cancer

Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia.

Cancer of unknown primary site