Disparities in survival by insurance status in patients with Hodgkin lymphoma.

BACKGROUND: The association between insurance status and outcomes has not been well established for patients with Hodgkin lymphoma (HL). The purpose of this study was to examine the disparities in overall survival (OS) by insurance status in a large cohort of patients with HL. METHODS: The National Cancer Data Base (NCDB) was used to evaluate patients with stage I to IV HL from 1998 to 2011. The association between insurance status, covariables, and outcomes was assessed in a multivariate Cox proportional hazards model. Survival was estimated with the Kaplan-Meier method. RESULTS: Among the 76,681 patients within the NCDB, 45,777 patients with stage I to IV HL were eligible for this study (median follow-up, 6.0 years). The median age was 39 years (range, 18-90 years). The insurance status was as follows: 3247 (7.1%) were uninsured, 7962 (17.4%) had Medicaid, 30,334 (66.3%) had private insurance, 3746 (8.2%) had managed care, and 488 (1.1%) had Medicare. Patients with an unfavorable insurance status (Medicaid/uninsured) were at a more advanced stage, had higher comorbidity scores, had B symptoms, and were in a lower income/education quartile (all P < .01). These patients were less likely to receive radiotherapy and start chemotherapy promptly and were less commonly treated at academic/research centers (all P < .01). Patients with unfavorable insurance had a 5-year OS of 54% versus 87% for those favorably insured (P < .01). When adjustments were made for covariates, an unfavorable insurance status was associated with significantly decreased OS (hazard ratio, 1.60; 95% confidence interval, 1.34-1.91; P < .01). The unfavorable insurance status rate increased from 22.8% to 28.8% between 1998 and 2011. CONCLUSIONS: This study reveals that HL patients with Medicaid and uninsured patients have outcomes inferior to those of patients with more favorable insurance. Targeting this subset of patients with limited access to care may help to improve outcomes. Cancer 2015;121:3435-43. © 2015 American Cancer Society.

Vitamin D and breast cancer.

In addition to its role in calcium homeostasis and bone health, vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer. The discovery that breast epithelial cells possess the same enzymatic system as the kidney, allowing local manufacture of active vitamin D from circulating precursors, makes the effect of vitamin D in breast cancer biologically plausible. Preclinical and ecologic studies have suggested a role for vitamin D in breast cancer prevention. Inverse associations have also been shown between serum 25-hydroxyvitamin D level (25(OH)D) and breast cancer development, risk for breast cancer recurrence, and mortality in women with early-stage breast cancer. Clinical trials of vitamin D supplementation, however, have yielded inconsistent results. Regardless of whether or not vitamin D helps prevent breast cancer or its recurrence, vitamin D deficiency in the U.S. population is very common, and the adverse impact on bone health, a particular concern for breast cancer survivors, makes it important to understand vitamin D physiology and to recognize and treat vitamin D deficiency. In this review, we discuss vitamin D metabolism and its mechanism of action. We summarize the current evidence of the relationship between vitamin D and breast cancer, highlight ongoing research in this area, and discuss optimal dosing of vitamin D for breast cancer prevention.

Characterization of Second Primary Malignancies in Mucosa-Associated Lymphoid Tissue Lymphomas: A SEER Database Interrogation.

INTRODUCTION: Second primary malignancies (SPMs) are long-term complications in cancer survivors. Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent extra-nodal marginal zone lymphomas, the majority of which typically have long-term survival. In this study, we investigated the incidence and pattern of SPMs in adult patients diagnosed with MALT lymphomas between January 2000 and December 2016. METHODS: Using the SEER-18 database and multiple primary standardized incidence ratio (MP-SIR) session of SEER stat software for statistical analysis, we assessed SPMs in MALT lymphomas. RESULTS: During this time, a total of 12,500 cases of MALT lymphomas were diagnosed, of which 1466 patients developed 1626 SPMs (O/E ratio: 1.48, 95% CI:1.41-1.55, P<.001). The median latency period for development of SPMs was 54 months (range 6-201 months). Secondary non-Hodgkin lymphomas, as defined by SEER as distinct from the primary lymphoma, was the most common SPM with 299 cases, followed by lung cancer (O/E ratio: 6.15, 95% CI:5.47-6.89, P<.0001). There were 898 SPMs that developed between 6- 59 months (O/E ratio: 1.47, 95% CI:1.37-1.57, P<.0001) and 728 after 60 months latency (O/E ratio: 1.5, 95% CI:1.39-1.61, P<.0001) after diagnosis of the primary MALT lymphomas. An increased incidence of both solid and hematologic cancers occurred in patients as early as 6 months after diagnosis of MALT lymphoma. CONCLUSION: These findings indicate that despite the indolent nature of most MALT lymphomas, there is an increased risk for SPMs warranting long-term follow up.

Impaired Humoral Immunity to SARS-CoV-2 Vaccination in Non-Hodgkin Lymphoma and CLL Patients.

Patients with hematologic malignancies are a high priority for SARS-CoV-2 vaccination, yet the benefit they will derive is uncertain. We investigated the humoral response to vaccination in 53 non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or CLL patients. Peripheral blood was obtained 2 weeks after first vaccination and 6 weeks after second vaccination for antibody profiling using the multiplex bead-binding assay. Serum IgG, IgA, and IgM antibody levels to the spike specific receptor binding domain (RBD) were evaluated as a measure of response. Subsequently, antibody-positive serum were assayed for neutralization capacity against authentic SARS-CoV-2. Histology was 68% lymphoma and 32% CLL; groups were: patients receiving anti-CD20-based therapy (45%), monitored with disease (28%), receiving BTK inhibitors (19%), or chemotherapy (all HL) (8%). SARS-CoV-2 specific RBD IgG antibody response was decreased across all NHL and CLL groups: 25%, 73%, and 40%, respectively. Antibody IgG titers were significantly reduced (p < 0.001) for CD20 treated and targeted therapy patients, and (p = 0.003) for monitored patients. In 94% of patients evaluated after first and second vaccination, antibody titers did not significantly boost after second vaccination. Only 13% of CD20 treated and 13% of monitored patients generated neutralizing antibodies to SARS-CoV-2 with ICD50s 135 to 1767, and 445 and > 10240. This data has profound implications given the current guidance relaxing masking restrictions and for timing of vaccinations. Unless immunity is confirmed with laboratory testing, these patients should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals. STATEMENT OF TRANSLATIONAL RELEVANCE: Non Hodgkin lymphoma (NHL) and Chronic Lymphocytic leukemia (CLL) patients who are treated with anti-CD20 antibody therapy, BTK inhibitor therapy, or who are monitored with active disease, have decreased antibody response to SARS-CoV-2 vaccination and decreased antibody titers compared to healthy controls. Antibody titers do not boost following second vaccination, and very few patients generate neutralizing antibodies against SARS-CoV-2. This data is of particular importance, given the recent guidance from the CDC that vaccinated patients no longer need to be masked indoors as well as outdoors. Patients with NHL or CLL who fall into these categories should not consider their immunity from vaccination to be assured. If infected with SARS-CoV-2, they should be a high priority for monoclonal antibody directed therapy. Unless immune response to vaccination is confirmed with laboratory testing, they should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.

Systemic approaches for multifocal bronchioloalveolar carcinoma: is there an appropriate target?

Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features. While the incidence of pure BAC is rare, comprising only 1% to 4% of non-small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas--and that figure may be increasing. Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies. Current options for multifocal BAC include both surgery and systemic therapies. Unfortunately, prospective data on systemic approaches are limited by study design and small patient numbers; there are only seven phase II studies involving four therapies. This article evaluates key characteristics of BAC, including the current understanding of histopathology and tumor biology. In addition, it comprehensively reviews the systemic phase II studies in an attempt to clarify the therapeutic challenges in this disease. It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.

Radiation Dose Reduction in Early-Stage Hodgkin Lymphoma.

INTRODUCTION: Treatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010. PATIENTS AND METHODS: The National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease. RESULTS: Of 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P < .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P < .001). The use of doses > 36 Gy decreased over a corresponding time period (OR 0.44, P < .001). CONCLUSION: Analysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses > 36 Gy.

Phase II trial of erlotinib and capecitabine for patients with previously untreated metastatic colorectal cancer.

BACKGROUND: This Simon 2-stage phase II trial was designed to document antitumor activity of capecitabine in combination with erlotinib in patients with previously untreated metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Time to tumor progression, objective response rate, and time to treatment failure were to be assessed. Secondary objectives included determination of toxicity. This trial was closed prematurely because of slower-than-expected accrual. Thirteen patients were enrolled, and all are off protocol treatment at the time of this report. RESULTS: Notably, 4 subjects discontinued therapy because of adverse events. Of 10 evaluable patients, 1 attained a complete response, 1 attained a partial response, 3 had stable disease, and 5 had progressive disease. Median time to disease progression was 21 weeks, with a range of 8-85 weeks. Overall survival ranged from 12 weeks to 182 weeks, with a median of 76 weeks. CONCLUSION: The toxicities and challenge to complete accrual observed in this trial are consistent with the experience of others attempting to develop erlotinib as part of combination treatment for advanced CRC.

Survival of Asian Females With Advanced Lung Cancer in the Era of Tyrosine Kinase Inhibitor Therapy.

INTRODUCTION: We examined the effect of access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on survival for Asian female (AF) EGFR mutation-enriched patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results database to study patients with stage IV lung adenocarcinoma diagnosed from 1998 to 2012. We compared survival (lung cancer-specific survival [LCSS] and overall survival) between AFs and non-Asian males (NAMs), an EGFR mutation-enriched and EGFR mutation-unenriched population, respectively, with a diagnosis in the pre-EGFR TKI (1998-2004) and EGFR TKI (2005-2012) eras. We used Cox proportional hazards models to examine the interaction of access to TKI treatment and EGFR enrichment status. RESULTS: Among 3029 AF and 35,352 NAM patients, we found that LCSS was best for AFs with a diagnosis in the TKI era (median, 14 months), followed by AFs with a diagnosis in the pre-TKI era (median, 8 months), NAMs with a diagnosis in the TKI era (median, 5 months), and NAMs with a diagnosis in the pre-TKI era (median, 4 months; log-rank P < .0001). In a multivariable model, the effect of a diagnosis in the TKI era on survival was greater for AFs than for NAMs (LCSS, P = .0020; overall survival, P = .0007). A lung cancer diagnosis in the TKI era was associated with an overall mortality decrease of 26% for AFs (hazard ratio, 0.740; 95% confidence interval, 0.682-0.80) and 15.9% for NAMs (hazard ratio, 0.841; 95% confidence interval, 0.822-0.860). CONCLUSIONS: We found increased survival for lung adenocarcinoma diagnoses made after widespread access to EGFR TKIs, with the greatest increase among AF patients enriched for EGFR mutations. The present analysis eliminated the effect of crossover, which has complicated assessments of the survival advantage in EGFR TKI randomized trials.

Association of intensity-modulated radiation therapy on overall survival for patients with Hodgkin lymphoma.

PURPOSE: The purpose of this study was to compare outcomes with Hodgkin lymphoma (HL) patients receiving IMRT (intensity-modulated radiation therapy), versus those receiving 2D/3D-CRT (3-dimensional conformal RT) in a large observational cohort. PATIENTS AND METHODS: We evaluated patients diagnosed with stage I-IV HL from 1998 to 2011 from the National Cancer Database (NCDB). The association between IMRT use vs. 2D/3D-CRT, co-variables, and outcome was assessed in a Cox proportional hazards model. Propensity score (PS) matching was performed to balance known confounding factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 76,672 patients with HL within the NCDB, 12,393 patients with stage I-IV HL received RT (median dose=30.6 Gy) and were eligible for this study, and 6013 patients analyzed for overall survival. The cohort had a median follow-up of 6.2 years and median age of 37 years (range: 18-90). The RT modalities used were: 2D/3D-CRT (n=11,491, 92.7%) or IMRT (n=902, 7.3%). Patients were more likely to receive IMRT if they were of male gender, early stage, no "B" symptoms, and treated at comprehensive cancer programs (all p<0.05). During this time period, there was a significant decrease in use of 2D/3D-CRT from 100% to 81.5%, with a subsequent increase in IMRT utilization from 0% to 18.5%. Five-year overall survival for patients receiving 2D/3D-CRT (n=5844) was 89.9% versus 95.2% for those receiving IMRT (n=169; HR=0.45; 95% CI, 0.23-0.91, p=0.02). After PS-matching based on clinicopathologic characteristics, IMRT use remained associated with improved overall survival (HR=0.40; 95% CI, 0.16-0.97, p=0.04). CONCLUSIONS: Our study reveals that HL patients receiving modern RT techniques were associated with an improvement in overall survival. This may have been related to patient selection, access to improved staging and management, or improvements in treatment technology. This represents the only study examining survival outcomes of advanced RT modalities, which may be considered on a case-by-case basis for highly selected patients with HL.

Impact of delays in definitive treatment on overall survival: a National Cancer Database study of patients with Hodgkin lymphoma.

The purpose of this large observational study was to examine outcomes in patients with Hodgkin lymphoma (HL) by timing to definitive chemotherapy (TTC) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998-2011, 56,457 patients with stage I-IV HL were studied, with a median follow-up of 6.0 years (median age=39). Median TTC was 26 days from diagnosis. The cohort of "early" (<60 days from diagnosis) TTC patients included 45,307 (80.3%) patients and "late" (≥60 days) TTC was 11,150 (19.7%). Patients were more likely to experience early TTC if they were of a younger age, at an advanced stage, with "B" symptoms, favorably insured, favorable socioeconomic status, and treated at comprehensive cancer center (all p<0.05). Ten-year overall survival for patients with early TTC was 73.2% vs. 70.0% for those with late TTC (HR=0.87; 95%CI, 0.83-0.92, p<0.0001). After PS-matching for co-variates, early TTC was not associated with overall survival (HR=0.96; 95%CI, 0.85-1.08, p=0.51). This represents the only study to evaluate overall survival by time to definitive treatment for HL.

Early-stage nodular lymphocyte-predominant Hodgkin lymphoma: the impact of radiotherapy on overall survival.

The purpose of this study was to use the National Cancer Database to examine the association between radiation therapy (RT) and overall survival (OS) in early-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998-2011, 1915 patients with stage I/II NLPHL were studied, with a median follow-up of 6.6 years (median age = 44). Of the cohort, 1224(64%) received RT (alone or with chemotherapy) to a median dose of 30.6 Gy. Patients were more likely to receive RT if male, younger age, lower stage, no "B"-symptoms, favorably insured, and treatment at comprehensive centers (all p < 0.05). Patients administered RT had an improved 5-year OS (HR = 0.62; 95%CI, 0.43-0.89, p = 0.01). After PS-matching (n = 868) based on all known co-variates, RT use trended towards improved OS (HR = 0.49; 95%CI, 0.23-1.05, p = 0.06). This study represents one of the largest prospective datasets examining the role of RT for stage I/II NLPHL and inclusion of RT may be considered.

Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival.

PURPOSE: To evaluate the efficacy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) induction therapy in patients with newly diagnosed mantle-cell lymphoma (MCL). PATIENTS AND METHODS: From March 1997 to May 1999, 40 previously untreated patients with stage II through IV MCL were treated with six cycles of rituximab and CHOP chemotherapy in a phase II trial. Pretreatment and interval peripheral-blood (PB) and bone marrow (BM) specimens were also analyzed by polymerase chain reaction (PCR) for tumor-specific BCL-1/immunoglobulin H (IgH) translocations and clonal IgH rearrangements. Study end points included clinical and molecular response rates and long-term progression-free survival (PFS). RESULTS: Forty-eight percent of patients achieved a complete response (CR)/CR unconfirmed (CRu), and 48% of patients obtained a partial response (PR). However, 28 of the 40 patients have already relapsed or developed progressive disease with a median PFS of 16.6 months. Twenty-five patients had PCR-detectable BCL-1/IgH or clonal IgH products in PB or BM at diagnosis. Nine of the 25 informative patients had no evidence of PCR-detectable disease in PB or BM after rituximab and CHOP therapy. However, patients who achieved molecular remissions in PB or BM had PFS similar to patients without molecular remissions (16.5 v 18.8 months, P =.51). CONCLUSION: Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibody-based in vivo purging in subsequent clinical trials.

Empowering targeted therapy: lessons from rituximab.

Rituximab, a monoclonal antibody directed against the B cell-specific protein CD20, has revolutionized lymphoma treatment by providing a highly effective form of therapy with relatively mild toxic side effects. Effective as a single agent against some forms of B cell lymphoma, rituximab also has a chemosensitizing effect, enhancing the efficacy of chemotherapy against other forms of the disease. Although the mechanisms whereby rituximab achieves its effects remain incompletely understood, these seem to involve at least three distinct phenomena: (i) antibody-dependent cell-mediated cytotoxicity, (ii) complement-mediated cell lysis, and (iii) stimulation of apoptosis in target cells. The latter occurs through interaction of complexes of rituximab and CD20 in lipid rafts, with elements of a signaling pathway involving Src kinases. Effector molecules trigger various gene expression events, leading to sensitization of malignant cells to proapoptotic stimuli. Lessons learned from the research on rituximab may be applied to the rational development of antibody-based therapies against other forms of cancer.

The horizon of antiangiogenic therapy for colorectal cancer.

Vascular endothelial growth factor (VEGF) plays a crucial role in the growth and metastatic spread of cancer. Bevacizumab (Avastin) is the first commercially available VEGF inhibitor, earning U.S. Food and Drug Administration (FDA) approval in February 2004. In combination with fluorouracil (5-FU)-based chemotherapy, this agent significantly prolongs overall and progression-free survival of patients with metastatic colorectal cancer. This review details the emerging role of the drug, its unique side effects, and other practical considerations related to bevacizumab therapy. Ongoing trials attempting to define additional indications for bevacizumab as well as the development of other promising angiogenesis inhibitors are also reviewed.

Early-Stage Classic Hodgkin Lymphoma: The Utilization of Radiation Therapy and Its Impact on Overall Survival.

PURPOSE: To examine the association between radiation therapy (RT) utilization and overall survival (OS) for patients with early-stage Hodgkin lymphoma (HL). METHODS AND MATERIALS: Using the National Cancer Database, we evaluated clinical features and survival outcomes among patients diagnosed with stage I/II HL from 1998 to 2011. The association between RT use, covariables, and outcome was assessed in a Cox proportional hazards regression model. Propensity score matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Among the 41,943 patients in the National Cancer Database with stage I/II HL, 29,752 patients were analyzed for this study. Radiation therapy use was associated with younger age (≤40 years), favorable insured status, higher socioeconomic status (income, education), and treatment at comprehensive community cancer centers (all P<.05). Five-year OS for patients receiving RT was 94.5%, versus 88.9% for those not receiving RT (P<.01). Radiation therapy use was a significant predictor of OS in the "As-Treated" cohort (hazard ratio 0.53, 95% confidence interval 0.49-0.58, P<.01) and intention-to-treat analysis (P<.01). After propensity score matching based on clinicopathologic characteristics, RT use remained associated with improved OS (hazard ratio 0.46, 95% confidence interval 0.38-0.56, P<.01). Over the study period, RT utilization for this cohort decreased from 55% to 44%, most commonly because it was not part of the planned initial treatment strategy. CONCLUSIONS: Consolidation RT was associated with improved OS for patients with early-stage classic HL. We also have identified patient-specific variations in the use of RT that may be targeted to improve patient access to care.

Long-term outcomes and patterns of failure in orbital lymphoma treated with primary radiotherapy.

The purpose of this study was to evaluate the long-term outcome and patterns of failure in patients treated with primary radiotherapy (RT) for orbital lymphoma (OL). Seventy-nine patients diagnosed with stage IE OL between 1995 and 2012 were included. Fifty-nine patients (75%) had mucosa-associated lymphoid tissue lymphoma and 20 patients (25%) had follicular lymphoma subtype. The median follow-up was 49.7 months. Major tumor sites were conjunctiva (29%), orbit (47%) and lacrimal gland (24%). After treatment to a median dose of 30.6 Gy, there were a total of no local, one contralateral orbital, two regional and two distant recurrences, all outside of the treatment fields. The 10-year local relapse-free, distant metastasis-free and overall survival rates were 100%, 94.2% and 98.2%, respectively. Definitive RT to 30 Gy was shown to be highly effective for indolent OL, and this study represents one of the largest single-institution studies using primary RT for stage IE OL.

The role of rituximab and chemotherapy in aggressive B-cell lymphoma: a preliminary report of dose-adjusted EPOCH-R.

Accumulating evidence suggests that the ability to activate apoptotic pathways may be an important determinant of chemotherapy sensitivity and presents a potentially important new therapeutic strategy. Monoclonal antibodies against the CD20 antigen directly induce apoptosis and may serve to modulate the threshold for chemotherapy-induced apoptosis. Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA), a monoclonal antibody against CD20, was combined with dose-adjusted EPOCH (infusional etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) chemotherapy and tested in 38 untreated or relapsed poor-prognosis aggressive lymphomas. Twenty-three patients were untreated. Of these patients, all had large B-cell histologies, a median age of 52 years, Eastern Cooperative Oncology Group performance status > or = 2 in 30%, and high-intermediate or high International Prognostic Index scores in 61%. Fifteen patients had relapsed or refractory lymphomas. These patients had received a median of two (range, one to four) prior regimens, 67% had aggressive histologies, and 60% had high-intermediate or high International Prognostic Index scores. Complete remissions were achieved in 85% and 64% of untreated and previously treated patients, respectively; additionally 42% of patients with disease refractory before therapy achieved complete remission. At a median follow-up of 12 months, progression-free and overall survival in the previously untreated group was 85% and 79%, respectively, and no patient in complete remission has relapsed. These results suggest that rituximab may modulate the sensitivity of B-cell lymphomas to chemotherapy.

A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer.

This study was designed to evaluate the efficacy and toxicity of the immunotoxin N901-blocked ricin (bR) in patients with small-cell lung cancer (SCLC) who achieved a complete or near-complete response following chemotherapy and/or radiation. Treatment consisted of a 7-day continuous infusion of N901-bR at a dose of 30 mg/kg/day followed by patient evaluation with repeat scans. Serum immunotoxin levels, human antimurine antibodies, and antiricin antibodies were determined during the course of the infusion. Nine patients enrolled in the study before it closed following a treatment-related death. Seven patients had extensive-stage disease and entered the study with a more than 90% reduction of their original tumor. Two patients with limited-stage SCLC had no evidence of disease at study entry. Maximum plasma levels of N901-bR ranged from 72-371 ng/mL. Laboratory toxicity consisted of transient transaminitis in 8 patients and creatine kinase elevation in 3 patients, 1 of whom developed premature ventricular contractions. One patient experienced progressive capillary leak syndrome following immunotoxin infusion, which proved fatal. All patients developed antibodies to the infused murine antibody as well as to the toxin. Six patients died of progressive SCLC and 1 patient died of presumed radiation pneumonitis. One patient with limited-stage disease is still alive more than 6 years after therapy. N901-bR therapy was associated with a fatal incident of capillary leak syndrome and a nearly universal development of human antimouse and antiricin antibodies, which limited its further clinical development.

Gallbladder and biliary tract carcinoma: A comprehensive update, Part 2.

Gallbladder carcinoma and carcinoma of the bile ducts are relatively rare cancers in the United States. These cancers are often diagnosed in an advanced stage due to their nonspecific symptomatology and until recently have been associated with a dismal prognosis. Recent advances in imaging and surgical techniques along with emerging options in palliative chemotherapy have improved the outlook in these cancers. While complete surgical resection remains the only hope of cure in both these cancers, palliative biliary decompression and chemotherapy result in substantial improvement in quality of life. Part 1 of this review, which appeared in last month's issue, provided a relevant and comprehensive update of molecular pathology, imaging modalities, and surgical care. In part 2, we examine palliative care and systemic therapy in gallbladder and biliary tract carcinomas, as well as the use of liver transplantation in the treatment of cholangiocarcinomas. These strategies are of relevance to internists as well as oncologists caring for these patients.