Search Results

Thyroid carcinoma has a unique biologic behavior characterized by early spread to regional lymph nodes and occasional extrathyroidal soft tissue extension but a low incidence of distant metastasis and infrequent disease-related death. Therefore, controversy exists over the proper extent of thyroidectomy and regional lymph node dissection in patients with differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). The modest disease-specific mortality makes it unlikely that the extent of surgery will ever be the subject of a prospective randomized trial. Although more extensive cervical surgery may have only a limited effect on the duration of survival in patients with DTC, it may significantly improve quality of life by minimizing cervical recurrence. The high rates of cervical recurrence in patients with DTC and MTC have alerted physicians to the importance of fine-needle aspiration biopsy and ultrasonography for the diagnosis, preoperative staging, and follow-up of thyroid cancer. In patients with MTC, death caused by disease is uncommon in the absence of radiographically evident distant metastasis at the time of thyroidectomy. Cervical recurrence is even more common with MTC, and the need for compartment-oriented lymphadenectomy is accepted as standard surgical treatment to minimize disease recurrence. Postoperatively, calcitonin (CT) levels can be used to guide clinical management, but basal CT levels should not be used to direct the timing of prophylactic thyroidectomy in affected high-risk patients with familial MTC.

T-cell large granular lymphocytic (T-LGL) leukemia after hematopoietic stem cell transplantation (SCT) is rare and its natural history and clinical outcome have not been well described. We report the clinical, morphologic, immunophenotypic, and molecular features of a case of donor-derived T-LGL leukemia in a 16-year-old man who received allogeneic SCT for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The patient presented with persistent neutropenia and splenomegaly 9 months after SCT when the chimerism study showed a 100% donor pattern. A splenectomy revealed T-LGL leukemia. Flow cytometric analysis showed an aberrant T-cell population positive for CD3, CD5 (dim, subset), CD7, CD8, CD16 (subset), CD57, CD94 (dim, partial), and T-cell receptor (TCR) αβ, and negative for CD4, CD26, CD56, and TCRγδ. Molecular studies showed monoclonal TCRβ and TCRγ gene rearrangements. Both the immunophenotype and molecular profile of the T-LGL leukemia were different from the pre-SCT PTCL. Sequencing analysis for STAT3 exon 21 did not reveal any mutation in both pre-SCT and post-SCT specimens. The patient did not receive any treatment for T-LGL leukemia; however, his count progressively increased after splenectomy, despite the presence of persistent T-LGL leukemia in the bone marrow. There was no evidence of recurrent PTCL. We propose an algorithm to diagnose this rare post-SCT neoplasm.

Background: JAK2 V617F mutation (mut) in acute myeloid leukemia (AML) is rare. We describe the clinicopathologic findings of a single-institution series of 11 de novo AML cases with JAK2 V617. Methods: We identified cases of de novo AML with JAK2 V617F over a 10-year period. We reviewed diagnostic peripheral blood and bone marrow (BM) morphologic, cytogenetic, and molecular studies, including next-generation sequencing. The control group consisted of 12 patients with JAK2 wild-type (wt) AML matched for age, sex, and diagnosis. Results: We identified 11 patients (0.5%) with JAK2 V617F, with a median age at diagnosis of 72.5 years (range, 36–90 years). Ten neoplasms were classified as AML with myelodysplasia-related changes and 1 as AML with t(8;21)(q22;q22). All JAK2mut AML cases showed at least bilineage dysplasia, 7 of 11 showed fibrosis, 8 of 11 had an abnormal karyotype, and 5 had deletions or monosomy of chromosomes 5 and 7. Using the European LeukemiaNet (ELN) classification, 9 patients (82%) with JAK2mut AML were intermediate-2 and adverse risk. Cases of JAK2mut AML did not have mutations in other activating signaling pathways (P=.013); 7 (64%) showed additional mutations in at least one gene involving DNA methylation and/or epigenetic modification. Patients with JAK2mut AML had a significantly higher median BM granulocyte percentage (12% vs 3.5%; P=.006) and a higher frequency of ELN intermediate-2 and adverse risk cytogenetics (P=.04) compared with those with JAK2wt AML. JAK2mut AML showed higher circulating blasts, but this difference was not significant (17% vs 5.5%; P=not significant). No difference was seen in the median overall survival rate of patients with JAK2mut AML versus those with JAK2wt AML (14 vs 13.5 months, respectively). Conclusions: De novo JAK2mut AML is rare and frequently found in patients with dysplasia, BM fibrosis, and abnormal karyotype with intermediate- or high-risk features; gene mutations in DNA methylation and epigenetic-modifying pathways; and absence of gene mutations in activating signaling pathways.

Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.

Background: This study aimed to determine the clinical relevance of putative radiographic and serologic metrics of chemotherapy response in patients with localized pancreatic cancer (LPC) who do not undergo pancreatectomy. Studies evaluating the response of LPC to systemic chemotherapy have focused on histopathologic analyses of resected specimens, but such specimens are not available for patients who do not undergo resection. We previously showed that changes in tumor volume and CA 19-9 levels provide a clinical readout of histopathologic response to preoperative therapy. Methods: Our institutional database was searched for patients with LPC who were treated with first-line chemotherapy between January 2010 and December 2017 and did not undergo pancreatectomy. Radiographic response was measured using RECIST 1.1 and tumor volume. The volume of the primary tumor was compared between pretreatment and posttreatment images. The percentage change in tumor volume (%Δvol) was calculated as a percentage of the pretreatment volume. Serologic response was measured by comparing pretreatment and posttreatment CA 19-9 levels. We established 3 response groups by combining these metrics: (1) best responders with a decline in %Δvol in the top quartile and in CA 19-9, (2) nonresponders with an increase in %Δvol and in CA 19-9, and (3) other patients. Results: This study included 329 patients. Individually, %Δvol and change in CA 19-9 were associated with overall survival (OS) (P≤.1), but RECIST 1.1 was not. In all, 73 patients (22%) were best responders, 42 (13%) were nonresponders, and there were 214 (65%) others. Best responders lived significantly longer than nonresponders and others (median OS, 24 vs 12 vs 17 months, respectively; P<.01). A multivariable model adjusting for type of chemotherapy regimen, number of chemotherapy doses, and receipt of radiotherapy showed that best responders had longer OS than did the other cohorts (hazard ratio [HR], 0.35; 95% CI, 0.21–0.58 for best responders, and HR, 0.55; 95% CI, 0.37–0.83 for others). Conclusions: Changes in tumor volume and serum levels of CA 19-9—but not RECIST 1.1—represent reliable metrics of response to systemic chemotherapy. They can be used to counsel patients and families on survival expectations even if pancreatectomy is not performed.

Background: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. Methods: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. Results: A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, “molecular profiling/diagnostics” was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)–certified laboratory. Conclusions: Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care.

Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.

Background: Among patients with localized esophageal cancer (LEC), 35% or more develop distant metastases (DM) as first relapse, most in the first 24 months after local therapy. Implementation of novel strategies may be possible if DM can be predicted reliably. We hypothesized that clinical variables could help generate a DM nomogram. Patients and Methods: Patients with LEC who completed multimodality therapy were analyzed. Various statistical methods were used, including multivariate analysis to generate a nomogram. A concordance index (c-index) was established and validated using the bootstrap method. Results: Among 629 patients analyzed (356 trimodality/273 bimodality), 36% patients developed DM as first relapse. The median overall survival from DM was only 8.6 months (95% CI, 7.0–10.2). In a multivariate analysis, the variables associated with a higher risk for developing DM were poorly differentiated histology (hazard ratio [HR], 1.76; P<.0001), baseline T3/T4 primary (HR, 3.07; P=.0006), and baseline N+ LEC (HR, 2.01; P<.0001). Although variables associated with a lower risk for DM were age of 60 years or older (HR, 0.75; P=.04), squamous cell carcinoma (HR, 0.54; P=.013), and trimodality therapy (HR, 0.58; P=.0001), the bias-corrected c-index was 0.67 after 250 bootstrap resamples. Conclusions: Our nomogram identified patients with LEC who developed DM with a high probability. The model needs to be refined (tumor and blood biomarkers) and validated. This type of model will allow implementation of novel strategies in patients with LEC.

Current algorithms for surveillance of patients with esophageal adenocarcinoma (EAC) after chemoradiation and surgery (trimodality therapy [TMT]) remain empiric. The authors hypothesized that the frequency, type, and timing of relapses after TMT would be highly associated with surgical pathology stage (SPS), and therefore SPS could be used to individualize the surveillance strategy. Between 2000 and 2010, 518 patients with EAC were identified who underwent TMT at The University of Texas MD Anderson Cancer Center and were frequently surveyed. Frequency, type, and timing of the first relapse (locoregional and/or distant) were tabulated according to SPS. Standard statistical approaches were used. The median follow-up time after esophageal surgery was 55.4 months (range, 1.0-149.2 months). Disease relapse occurred in 215 patients (41.5%). Higher SPS was associated with a higher rate of relapse (0/I vs II/III, P≤.001; 0/I vs II, P=.002; SPS 0/I vs III, P≤.001; and SPS II vs III, P=.005) and with shorter time to relapse (P<.001). Irrespective of the SPS, approximately 95% of all relapses occurred within 36 months of surgery. The 3- and 5-year overall survival rates were shorter for patients with a higher SPS than those with a lower SPS (0/I vs II/III, P≤.001; 0/I vs II, P≤.001; 0/I vs III, P≤.001; and II vs III, P=.014). The compelling data show an excellent association between SPS and frequency/type/timing of relapses after TMT in patients with EAC. Thus, the surveillance strategy can potentially be customized based on SPS. These data can inform a future evidence-based surveillance strategy that can be efficient and cost-effective.