A single case of rosai-dorfman disease marked by pathologic fractures, kidney failure, and liver cirrhosis treated with single-agent cladribine.

Rosai-Dorfman disease (RDD) is a proliferative histiocytic disorder of unknown etiology, which is characterized by sinus histiocytosis with massive lymphadenopathy (1). In most cases, RDD has a benign course and treatment is not necessary. However, severe cases of RDD require treatment, and the treatment strategy is determined on the basis of the severity of the disease or the extranodal involvement of vital organs. We report a single case of RDD with atypical presentation of persistent constitutional symptoms, progressing pathologic fractures, and end-organ dysfunction, including acute kidney failure and liver cirrhosis with esophageal varices.

Positron emission tomography/computed tomography findings during therapy predict outcome in patients with diffuse large B-cell lymphoma treated with chemotherapy alone but not in those who receive consolidation radiation.

PURPOSE: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). METHODS AND MATERIALS: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. RESULTS: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET-) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET- versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET- vs 52% PET+ [P=.012], OS 78% for PET- and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET- vs 81% PET+ [P=.88]; OS 90% PET- vs 81% PET+ [P=.39]). CONCLUSION: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update.

PURPOSE: To provide evidence-based recommendations to practicing oncologists, surgeons, and radiation therapy clinicians to update the 2005 clinical practice guideline on the use of sentinel node biopsy (SNB) for patients with early-stage breast cancer. METHODS: The American Society of Clinical Oncology convened an Update Committee of experts in medical oncology, pathology, radiation oncology, surgical oncology, guideline implementation, and advocacy. A systematic review of the literature was conducted from February 2004 to January 2013 in Medline. Guideline recommendations were based on the review of the evidence by Update Committee. RESULTS: This guideline update reflects changes in practice since the 2005 guideline. Nine randomized clinical trials (RCTs) met systematic review criteria for clinical questions 1 and 2; 13 cohort studies informed clinical question 3. RECOMMENDATIONS: Women without sentinel lymph node (SLN) metastases should not receive axillary lymph node dissection (ALND). Women with one to two metastatic SLNs planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND (in most cases). Women with SLN metastases who will undergo mastectomy should be offered ALND. These three recommendation are based on RCTs. Women with operable breast cancer and multicentric tumors, with ductal carcinoma in situ (DCIS) who will undergo mastectomy, who previously underwent breast and/or axillary surgery, or who received preoperative/neoadjuvant systemic therapy may be offered SNB. Women who have large or locally advanced invasive breast cancer (tumor size T3/T4), inflammatory breast cancer, or DCIS (when breast-conserving surgery is planned) or are pregnant should not undergo SNB. These recommendations are based on cohort studies and/or informal consensus. In some cases, updated evidence was insufficient to update previous recommendations.

NCCN Task Force Report: Bone Health In Cancer Care.

Bone health and maintenance of bone integrity are important components of comprehensive cancer care. Many patients with cancer are at risk for therapy-induced bone loss, with resultant osteoporotic fractures, or skeletal metastases, which may result in pathologic fractures, hypercalcemia, bone pain, and decline in motility and performance status. Effective screening and timely interventions are essential for reducing bone-related morbidity. Management of long-term bone health requires a broad knowledge base. A multidisciplinary health care team may be needed for optimal assessment and treatment of bone-related issues in patients with cancer. Since publication of the previous NCCN Task Force Report: Bone Health in Cancer Care in 2009, new data have emerged on bone health and treatment, prompting NCCN to convene this multidisciplinary task force to discuss the progress made in optimizing bone health in patients with cancer. In December 2012, the panel members provided didactic presentations on various topics, integrating expert judgment with a review of the key literature. This report summarizes issues surrounding bone health in cancer care presented and discussed during this NCCN Bone Health in Cancer Care Task Force meeting.

Clinical implications of positron emission tomography-negative residual computed tomography masses after chemotherapy for diffuse large B-cell lymphoma.

Response to primary treatment in diffuse large B-cell lymphoma (DLBCL) is highly predictive of long-term outcome. We evaluated the value of computed tomography (CT) findings relative to positron emission tomography (PET) findings, after the completion of chemotherapy. We retrospectively reviewed records from 491 patients with DLBCL at M. D. Anderson in 2001-2007; 22 patients were excluded for uncertain pathology and 169 for having received consolidative radiation, leaving 300 patients for the present analysis (median age, 61 years; 53% men, 47% women; 27% stage I-II, 73% stage III-IV; 73% completed 6-8 cycles of doxorubicin-based therapy). Factors associated with outcome on univariate analysis were response according to PET/CT and CT (p < 0.0001 for overall survival [OS], disease-specific survival [DSS] and progression-free survival [PFS]); number of chemotherapy cycles received (p < 0.0001 OS, p < 0.0001 DSS, p < 0.002 PFS); the combined presence of Ki-67 > 50%, PET SUV ≥ 13 and bulky (> 5 cm) disease (p = 0.005 OS, p = 0.001 DSS, p = 0.001 PFS); and International Prognostic Index (IPI) score (p = 0.004 OS, p = 0.005 DSS, p = 0.004 PFS). On multivariate analysis, PET/CT-negative, CT residual mass (> 2 cm) significantly influenced OS, DSS and PFS (p < 0.0001). The presence of a residual mass >2 cm on CT, coupled with negative findings on PET/CT, has prognostic value in DLBCL.

Multimodality therapy: bone-targeted radioisotope therapy of prostate cancer.

Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy.

PET/CT Imaging in Gynecologic Malignancies Other than Ovarian and Cervical Cancer.

Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is an imaging modality used for staging, assessing response to therapy, and diagnosis of recurrent cervical and ovarian cancer. The potential role of FDG-PET/CT in other gynecologic malignancies such as endometrial cancer, uterine sarcomas, vaginal, and vulvar cancer has not been fully explored.

Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates.

Point mutations in the KIT receptor tyrosine kinase gene have recently been identified in mucosal, acral lentiginous, and chronically sun-damaged melanomas. We have identified the first human melanoma cell line with an endogenous L576P mutation, the most common KIT mutation in melanoma ( approximately 30-40%). In vitro testing showed that the cell viability of the L576P mutant cell line was not reduced by imatinib, nilotinib, or sorafenib small molecule KIT inhibitors effective in nonmelanoma cells with other KIT mutations. However, the viability of the mutant cells was reduced by dasatinib at concentrations as low as 10 nM (P = 0.004). Molecular modeling studies found that the L576P mutation induces structural changes in KIT that reduce the affinity for imatinib (DeltaDeltaGbind = -2.52 kcal/mol) but not for dasatinib (DeltaDeltaGbind = +0.32 kcal/mol). Two metastatic melanoma patients with the L576P KIT mutation were treated with dasatinib, including one patient previously treated with imatinib. Both patients had marked reduction (>50%) and elimination of tumor F18-fluorodeoxyglucose (FDG)-avidity by positron emission tomography (PET) imaging after dasatinib treatment. These data support the selective inhibitory effect of dasatinib against cells harboring the most common KIT mutation in melanoma, and thus has therapeutic implications for acrallentiginous, chronic sun-damaged, and mucosal melanomas.

Pilot study of targeted skeletal radiation therapy for bone-only metastatic breast cancer.

PURPOSE: Bone-targeted radiation therapy is an attractive strategy for addressing bone disease with minimal systemic toxicity. This pilot study was designed to determine the safety and efficacy of (166)Holmium (Ho)-DOTMP for irradiating malignant cells and adjacent marrow in women with bone-only metastatic breast cancer. PATIENTS AND METHODS: Subjects included 6 women aged < or = 65 years with breast cancer and bone-only metastases at M. D. Anderson Cancer Center. The activity of (166)Ho-DOTMP was calculated to deliver a therapeutic absorbed dose of 22 Gy (n = 3) or 28 Gy (n = 3) to the marrow. Treatment was followed by autologous stem cell transplantation to circumvent the anticipated myelosuppresion. Median follow-up time was 40 months. RESULTS: All subjects showed prompt hematologic recovery. No patient experienced grade 3/4 acute toxicity aside from myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy. One patient developed myelodysplastic syndrome but was found to have had pre-existing trisomy 8. Two patients remained progression free without evidence of disease for more than 6 years. Five women experienced disease relapse (4 at extraosseous sites) and died of progressive disease. Median time to progression was 10.4 months. CONCLUSION: The approach of bone-targeted radiation therapy with (166)Ho-DOTMP had an acceptable toxicity profile, and sustained complete response was obtained in 2 of 6 patients. We are conducting a phase II study to evaluate the efficacy of targeted skeletal radiation therapy for treating bone-only metastases.

NCCN task force: clinical utility of PET in a variety of tumor types.

Use of PET is widespread and increasing in the United States, mainly for oncologic applications. In November 2006, the National Comprehensive Cancer Network (NCCN) gathered a panel of experts to review the literature and develop clinical recommendations for using PET scans in lymphoma and non-small cell lung, breast, and colorectal cancers. However, because its use is not restricted to these diseases, and evidence is accumulating for its application in other types of cancers, NCCN convened a second meeting in December 2008 to expand on the initial report. A multidisciplinary panel met to discuss the current data on PET application for various tumor types, including genitourinary, gynecologic, pancreatic, hepatobiliary, thyroid, brain, small cell lung, gastric, and esophageal cancers, and sarcoma and myeloma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, the role of PET in oncology, principles of PET use, emerging applications, and possible future developments.

Radiation dosimetry and biodistribution of (99m)Tc-ethylene dicysteine-deoxyglucose in patients with non-small-cell lung cancer.

PURPOSE: To assess the radiation dosimetry and biodistribution of (99m)Tc-labeled ethylene dicysteine deoxyglucose ((99m)Tc-EC-DG) in patients with non-small-cell lung cancer (NSCLC). METHODS: Serial whole-body scans were acquired 0, 2, 4, 6 and 24 h after injection of (99m)Tc-EC-DG (925 MBq) in seven NSCLC patients. Radiation dosimetry, blood clearance and SPECT imaging of the primary tumor were assessed. RESULTS: The critical organ was the bladder wall, with average radiation absorbed dose over all seven patients of 2.47x10(-2) mGy/MBq. The average effective dose equivalent and effective dose were 6.20x10(-3) mSv/MBq (6.89 mSv/1,110 MBq) and 5.90x10(-3) mSv/MBq (6.54 mSv/1,110 MBq), respectively. The primary tumor was visualized with SPECT in six patients. On final pathology, one patient had a granuloma, which did not enhance with (99m)Tc-EC-DG. CONCLUSION: (99m)Tc-EC-DG has acceptable dosimetric and biodistribution properties as a diagnostic tumor-imaging agent. Future studies are planned to evaluate its diagnostic potential.

PET/CT and occult primary tumors.

Within the past 5 years, F-18 fluorodeoxyglucose (FDG) PET/CT has become one of the more frequent imaging modalities in the management of patients with cancer of unknown primary origin. FDG PET/CT detects more sites of metastasis than other modalities, and in 20% to 40% of cases it discloses the site of the primary tumor. Its exact role is yet to be defined because of a lack of prospective clinical trials comparing the performance of PET/CT with conventional anatomic imaging modalities. This article reviews the available literature, attempts to place PET/CT using F-18-labeled FDG in clinical perspective and compares the combined modality with conventional anatomic imaging technologies.

Imaging of gastrointestinal stromal tumors and assessment of benefit from systemic therapy.

While gastrointestinal stromal tumors have been increasingly recognized with the prolonged survival and highly effective new targeted treatments, the role of imaging has become important not only for diagnosing and staging the tumors, but also for monitoring the effects of treatment and surveillance. Computed tomography is the imaging modality of choice for these purposes. Fluorine-18 fluorodeoxyglucose positron emission tomography is primarily used in problem solving when there are inconsistencies between CT and clinical findings or inconclusive CT images. The roles of MRI and ultrasound are also described.

PET and PET/CT in management of the lymphomas.

Within recent years, F-18 fluorodeoxyglucose (FDG) PET has become the most important nuclear medicine and radiology imaging modality in the management of lymphoma. FDG-PET detects more disease sites and involved organs than conventional staging procedures, including CT, and has a large influence on staging. FDG-PET performed during and after therapy seems to provide considerable prognostic information. The impact on patient outcome is not clear, however, because no controlled trials have yet been conducted and follow-up periods are generally short.

NCCN task force report: positron emission tomography (PET)/computed tomography (CT) scanning in cancer.

The use of positron emission tomography (PET) is increasing rapidly in the United States, with the most common use of PET scanning related to oncology. It is especially useful in the staging and management of lymphoma, lung cancer, and colorectal cancer, according to a panel of expert radiologists, surgeons, radiation oncologists, nuclear medicine physicians, medical oncologists, and general internists convened in November 2006 by the National Comprehensive Cancer Network. The Task Force was charged with reviewing existing data and developing clinical recommendations for the use of PET scans in the evaluation and management of breast cancer, colon cancer, non-small cell lung cancer, and lymphoma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, possible future developments, and the role of PET in oncology.

Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria.

PURPOSE: Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating gastrointestinal stromal tumors (GISTs) treated with imatinib. This study evaluates whether computed tomography (CT) findings of GIST after imatinib treatment correlate with tumor responses by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and develops reliable, quantitative, CT response criteria. PATIENTS AND METHODS: A total of 172 lesions selected by RECIST were evaluated in 40 patients with metastatic GISTs treated with imatinib. All patients had pretreatment and 2-month follow-up CTs and FDG-PETs. Multivariate analysis was performed using tumor size and density (Hounsfield unit [HU]) on CT and maximum standardized uptake value (SUVmax) on FDG-PET. Patients were observed up to 28 months. RESULTS: Mean baseline tumor size and density on CT were 5.3 cm and 72.8 HU, respectively, and mean baseline SUVmax on FDG-PET was 5.8. Thirty-three patients had good response on FDG-PET. A decrease in tumor size of more than 10% or a decrease in tumor density of more than 15% on CT had a sensitivity of 97% and a specificity of 100% in identifying PET responders versus 52% and 100% by RECIST. Good responders on CT at 2 months had significantly longer time to progression than those who did not respond (P = .01). CONCLUSION: Small changes in tumor size or density on CT are sensitive and specific methods of assessing the response of GISTs. If the prognostic value of our proposed CT response criteria can be confirmed prospectively, the criteria should be employed in future studies of patients with GIST.

We should desist using RECIST, at least in GIST.

PURPOSE: Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating imatinib-treated gastrointestinal stromal tumors (GISTs). Response by Choi criteria, a 10% decrease in size or a 15% decrease in density on contrast-enhanced CT, correlated well in a small training set of patients who showed response as measured by positron emission tomography, and was more predictive of time to tumor progression (TTP) than response by RECIST. This study was designed to validate these observations in an independent data set. PATIENTS AND METHODS: Fifty-eight patients with imatinib-treated GISTs were evaluated by RECIST and Choi criteria. TTP was compared with TTP in the training set. Patients were analyzed initially with follow-up to 28 months, extended to 60 months for survival analysis. RESULTS: Patients who met Choi response criteria on CT at 2 months had significantly better TTP than those who did not (P = .0002), whereas response group by RECIST was not significantly correlated with TTP. Even when the 98 patients from both sets were analyzed together, the response group by RECIST did not correlate significantly with TTP, whereas response group by Choi criteria did correlate significantly with TTP. Disease-specific survival (DSS) was also significantly correlated with response group by Choi criteria (P = .04), but not with response group by RECIST. CONCLUSION: Choi response criteria are reproducible, more sensitive, and more precise than RECIST in assessing the response of GISTs to imatinib mesylate. Response by Choi criteria, unlike response by RECIST, correlates significantly with TTP and DSS. Response by Choi criteria should be incorporated routinely into future studies of GIST therapy. We should desist using RECIST, at least in GIST.

Results of a retrospective single institution analysis of targeted skeletal radiotherapy with (166)Holmium-DOTMP as conditioning regimen for autologous stem cell transplant for patients with multiple myeloma. Impact on transplant outcomes.

(166)Holmium-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high-dose radiation to the bone marrow. Phase I/II trials showed feasibility and tolerability when combined with high-dose melphalan with or without total-body irradiation (TBI) in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). The purpose of this study was to define the potential impact of (166)Holmium-DOTMP on outcomes in patients with MM undergoing ASCT. Retrospective review of transplant outcomes among patients with MM who received an ASCT between January 1998 to December 2001 with either melphalan 200 mg/m(2) or a (166)Holmium-DOTMP containing regimen as part of their initial therapy. Univariate analysis was performed for response, overall survival (OS), and event free survival (EFS). One hundred four patients were identified, of which 41 received a (166)Holmium-DOTMP containing regimen and 63 received melphalan alone. The (166)Holmium-DOTMP patients were divided into 2 groups according to the dose received (<2400 mCi versus > or = 2400 mCi). The (166)Holmium-DOTMP group had a trend towards a higher complete remission (CR) rate compared to patients receiving melphalan alone (51% versus 32%). The median EFS for the low-dose (166)Holmium-DOTMP, the high-dose (166)Holmium-DOTMP, and melphalan alone was 30, 23, and 19 months, respectively; the OS rate at 5 years for the 3 groups was 61%, 40%, and 43%, respectively. (166)Holmium-DOTMP, in combination with high-dose melphalan, can result in higher CR rates when given in optimal doses (<2400 mCi) when compared to melphalan alone, and should be further tested in phase III trials in patients with MM undergoing ASCT.

Incidental findings on integrated PET/CT that do not accumulate 18F-FDG.

OBJECTIVE: The purpose of this study was to report the prevalence of abnormalities that do not show increased 18F-FDG uptake on the CT component of integrated PET/CT in patients with non-small cell lung cancer. MATERIALS AND METHODS: Images from all PET/CT studies performed consecutively between April and October 2003 on patients with non-small cell lung cancer were retrospectively reviewed. All abnormalities present on the CT component of the PET/CT scans that did not show abnormally increased 18F-FDG uptake were documented. RESULTS: Three hundred twenty-one patients with non-small cell lung cancer (179 men, 142 women; mean age, 67 years; age range, 38-91 years) underwent initial staging (198/321 [62%]) or restaging (123/321 [38%]) PET/CT imaging during the study period. In 263 (82%) of the patients, CT showed 1,231 abnormalities that were not 18F-FDG avid. The abnormalities were located in the thorax (n = 650), abdomen and pelvis (n = 444), head and neck (n = 69), and bony skeleton (n = 68). In total, 298 (24%) of the abnormalities that were not 18F-FDG avid were located outside the range of a standard thoracic CT scan. The clinical importance of these abnormalities was classified as major (n = 48 [4%]), moderate (n = 465 [38%]), or minor (n = 718 [58%]). Four (1%) of the patients had findings of major clinical importance that did not show increased 18F-FDG uptake and were previously unsuspected. CONCLUSION: Among patients with non-small cell lung cancer undergoing PET/CT, there is a high prevalence of CT abnormalities that do not show correlative 18F-FDG avidity but that may be clinically important.

Interobserver and intraobserver variability of standardized uptake value measurements in non-small-cell lung cancer.

OBJECTIVES: To assess interobserver and intraobserver variabilities in measuring the maximal standardized uptake value (SUV) of non-small-cell lung cancer. METHODS: Positron emission tomography-computed tomography examinations of 20 consecutive patients referred for initial evaluation of newly diagnosed non-small-cell lung cancer were retrospectively reviewed by 5 experienced positron emission tomography-computed tomography readers, who independently measured the maximal SUV/body weight of the primary tumors. Interobserver and intraobserver variabilities were assessed by using 4 statistical methods: correlation, regression analysis, Bland-Altman analysis, and analysis of variance. The SUV measurements derived in the study were compared with the SUV measurements documented in the original reports using correlation and regression analysis. The percentages of tumors whose retrospective SUV measurements were more than 20% different and more than 25% different from those in the original report were assessed. RESULTS: Both interobserver and intraobserver SUV measurements were highly reproducible. Pearson correlation coefficients were greater than 0.95 and 0.94, respectively. Good interobserver and intraobserver agreement was shown with regression analysis (F test P value >0.05), the Bland-Altman analysis, and analysis of variance (F test P value >0.95). The mean original SUV was much less than the mean study SUV (P<0.05). The study SUV differed from the SUV of the original report by more than 20% in 50% of the tumors, and by more than 25% in 45% of the tumors. CONCLUSIONS: There was excellent interobserver and intraobserver agreement in SUVs measured in the study environment but poor agreement between study SUVs and those documented in original reports, which can affect treatment decisions substantially.