Search

Purpose: Iron deficiency (ID) is a complication of gastrointestinal (GI) cancers that may manifest as iron deficiency anemia (IDA). Serum ferritin monitoring and oral iron supplementation have the limitations of being falsely elevated and poorly absorbed, respectively. This study aims to assess the discordance in surveillance, treatment practices, and awareness of ID/IDA in GI cancer patients by Canadian physicians treating these patients., Methods: From February 2020 to September 2021, a 22-question electronic survey was sent to medical oncologists (MOs), surgical oncologists (SOs), and gastroenterologists (GEs). The survey collected information about four domains: physician demographics, surveillance practices, treatment practices, and awareness of ID/IDA in GI cancer patients and ASCO/ASH guidelines., Results: A total of 108 (34 MOs, 19 SOs, and 55 GEs) of the 872 (12.4%) invited physicians completed the survey. Of these, 26.5% of MOs, 36.8% of SOs, and 70.9% of GEs measured baseline iron parameters, with few continuing surveillance throughout treatment. Ferritin was widely measured by MOs (88.9%), SOs (100%), and GEs (91.4%). Iron was supplemented if ID/IDA was identified pre-treatment by 66.7% of MOs, 85.7% of SOs, and 94.2% of GEs. Parenteral iron was prescribed by SOs (100%), while oral iron was prescribed by MOs (83.3%) and GEs (87.9%). Only 18.6% of physicians were aware of the ASCO/ASH guidelines regarding erythropoiesis-stimulating agents with parenteral iron for treating chemotherapy-induced anemia., Conclusion: Results illustrate variations in practice patterns for IDA management across the different physician specialties. Moreover, there appeared to be gaps in the knowledge and care surrounding evidence-based IDA management principles which may contribute to poor clinical outcomes.

Purpose: Plasma detection of EGFR T790M mutations is an emerging alternative to tumor rebiopsy in acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Validation of analytical sensitivity and clinical utility is required before routine diagnostic use in clinical laboratories., Patients and Methods: Sixty-three patients with advanced EGFR -mutant lung cancer at 7 Canadian centers, who were being screened for the ASTRIS trial (ClinicalTrials.gov identifier: NCT02474355), participated in this companion study. Plasma T790M mutation was detected using droplet digital polymerase chain reaction, Cobas (Roche Diagnostics, Indianapolis, IN), or next-generation sequencing in 4 laboratories. T790M concordance was assessed between plasma and tumor samples., Results: Assessment of T790M in tumor biopsy tissue was successful in 81% of patients; 49% had confirmed T790M results (tumor or plasma) for ASTRIS. Plasma testing in this companion study yielded T790M results in 97% of patients; 62% had T790M-positive results, 36% had negative results, and 2% had indeterminate results. Of 38 patients with negative or indeterminate biopsy results, 55% had positive plasma T790M results, increasing the proportion with T790M-positive results to 73%. Sensitivity of plasma T790M testing was 75%. Overall concordance between tissue and plasma was 64%, and concordance among laboratories was 90.3%. Response to osimertinib and duration of therapy were similar irrespective of testing method (overall response rate, 62.5% for tissue, 66.7% for plasma, and 70.6% for both)., Conclusion: This multicenter validation study demonstrates that plasma EGFR T790M testing can identify significantly more patients than biopsy alone who may benefit from targeted therapy.

Background: Locally recurrent rectal cancer (LRRC) is a complex problem requiring multidisciplinary consultation and specialized surgical care. Given the paucity of published longer-term survival data, skepticism persists regarding the benefit of major extirpative surgery. We investigated ultra-long-term (~15 years) outcomes following radical resection of LRRC and sought relevant clinicopathologic prognostic variables., Methods: A cohort of 52 consecutive patients who underwent resection of LRRC at our institution between 1997 and 2005 were followed with serial exams and imaging up to the point of death, or 30/06/2019., Results: Median follow-up time was 16.5 years (9.9-18.3) for patients who were alive at last follow-up; only one patient was lost to follow-up, at 9.9 years. For the entire cohort of 52 patients, disease-specific survival (DSS) at 5, 10, and 15 years following salvage surgery was 41%, 33%, and 31%, respectively. All patients who had distant metastatic disease at the time of LRRC resection (n = 6) subsequently died of cancer, at a median of 21 months (4-46). In those without distant metastases at time of salvage surgery (n = 46), DSS at 5, 10, and 15 years was 47%, 38%, and 35%, respectively, median 60 months. Negative resection margin (R0) was independently predictive of superior outcomes. In patients with M0 disease who had R0 resection (n = 37), DSS at 5, 10 and 15 years was 58%, 47%, and 44%, respectively, median 73 months. No patient developed re-recurrence after 5.5 years., Conclusions: This study demonstrates exceptionally durable long-term cancer-free survival following salvage surgery for LRRC, indicating that cure is possible., Competing Interests: Declaration of competing interest The authors have no conflicts of interest or funding source to declare., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Molecular aberrations in KRAS, NRAS, BRAF, and PIK3CA have been well-described in advanced colorectal cancer. The incidences of other mutations are less known. We report results of molecular profiling of advanced colorectal cancer in an academic cancer center., Patients and Methods: Patients with advanced colorectal were enrolled in an institution-wide molecular profiling program. Profiling was performed on formalin-fixed paraffin embedded archival tissues using a customized MassArray panel (23 genes, 279 mutations) or the Illumina MiSeq TruSeq Cancer Panel (48 genes, 212 amplicons, ≥ 500× coverage) in a Clinical Laboratory Improvement Amendments-certified laboratory. PTEN was determined by immunohistochemistry., Results: From March 2012 to April 2014, 245 patients were enrolled. At least one mutation was found in 54% (97/178) and 91% (61/67) of patients using MassArray or MiSeq platforms, respectively (P < .01). Of all patients, KRAS G12/13 mutation was identified in 39%, and non-G12/13 KRAS, BRAF, or NRAS mutations were present in 9%, 6%, and 4%, respectively. Other common mutations included TP53 (68.7%), APC (41.8%), and PIK3CA (13.5%). Co-mutation with KRAS, NRAS, or BRAF was found in 75% of patients with PIK3CA mutation. Of 106 patients with known PTEN immunohistochemistry status, 16% were negative. A higher average number of mutations were observed in right versus left colorectal cancer (P < .01), with 13 of 14 BRAF mutations located in right colon cancer., Conclusion: Mutations are common in advanced colorectal cancer. Right colon cancers harbor more genetic aberrations than left colon or rectal cancers. These aberrations may contribute to differential outcomes to anti-epidermal growth factor receptor therapy among patients with right colon, left colon, or rectal cancers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is a leading cause of tumor-related morbidity and mortality worldwide, with mortality most often attributable to metastatic disease. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, has a significant role in the treatment of metastatic CRC (mCRC). However, patient access to bevacizumab may be limited in some regions or circumstances, owing to factors related to insurance coverage, reimbursement, patient out-of-pocket costs, or availability. As a result, outcomes for patients with mCRC may be worsened. Additionally, counterfeit bevacizumab has infiltrated legitimate supply chains, exposing patients to risk. Oncologists may also be affected detrimentally, since resolving access issues can be time-consuming and demoralizing. The imminent expiry of patents protecting bevacizumab provides other manufacturers with the opportunity to produce highly similar versions known as biosimilars. High-quality, safe, and effective biosimilars have the potential to expand access to bevacizumab. Most of the bevacizumab biosimilars currently in development are in clinical trials in patients with non-small-cell lung cancer, and future authorization for mCRC indications will, therefore, be based on extrapolation. This article reviews the current role of bevacizumab in the management of mCRC, the possible barriers associated with diminished access to bevacizumab, and the potential bevacizumab biosimilars in development. How biosimilars may impact the treatment of mCRC is also discussed.

Introduction: Lung cancer is associated with higher levels of symptom distress and unmet needs than other cancer types. We assessed changes in symptoms, function, understanding, and preferences of patients with advanced lung cancer over a 10-year period., Materials and Methods: A 26-item self-administered questionnaire was used to assess symptom burden, functional impairment, knowledge of disease and treatment, and information preferences. The survey was administered to consecutive outpatients with advanced lung cancer first in 2002 and a second cohort in 2012., Results: A total of 108 patients with advanced lung cancer were surveyed in 2002, and 100 in 2012. Rates of severe physical symptoms were similar over the 10-year period. The most common symptoms remained fatigue, cough, and dyspnea. One-third perceived major impairment of daily activities from lung cancer. Significant anxiety was reported by at least 20%; nearly a quarter reported being unable to meet family needs. More patients in 2012 received information on treatment benefits, side effects, and clinical trials. Only 40% reported having end-of-life wishes, and fewer than half had discussed these with their oncologist. Over time, more patients expressed a preference for treatment associated with increased survival even if it compromised quality of life. Half were interested in Internet-based resources, most in print media, and a growing number in telephone support., Conclusion: Patients with advanced lung cancer continue to experience significant symptom distress and unmet needs despite advances in treatment. Comprehensive assessment and symptom, psychological, financial, and information support remain key areas for improvement in the care of patients with advanced lung cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Erlotinib is an epidermal growth factor receptor inhibitor approved for patients with advanced non-small-cell lung cancer (NSCLC) whose epidermal growth factor receptor expression status is positive or unknown. Although it is efficacious, erlotinib can cause skin toxicity. This prospective, randomized phase III trial examined the effect of prophylactic treatment of erlotinib-induced skin rash., Patients and Methods: Patients receiving erlotinib in the second- or third-line setting for advanced NSCLC were randomly assigned to prophylactic minocycline (100 mg twice per day for 4 weeks), reactive treatment (after rash developed, per grade of rash), or no treatment unless severe (grade 3). Rash incidence and severity, time to maximal rash, time to resolution, and overall survival (OS) were compared among treatment groups., Results: In all, 150 patients were randomly assigned, 50 to each of three treatment arms. The incidence of skin toxicity was 84% regardless of treatment arm. Prophylactic treatment with minocycline significantly lengthened the time to the most severe grade of rash. Grade 3 rash was significantly higher in the no-treatment arm. OS was not significantly different among treatment arms, but patients receiving prophylactic or reactive treatments had a longer OS (7.6 and 8 months, respectively) than those who received no rash treatment (6 months). Rash was not self-limiting., Conclusion: The incidence of all grades of rash did not differ statistically among the three arms, so the trial was negative. The incidence of grade 3 skin toxicities was reduced in patients who were treated with prophylactic minocycline or reactive treatment. Efficacy was not compromised. Prophylactic minocycline and reactive treatment are both acceptable options for the necessary treatment of erlotinib-induced rash in the second- or third-line setting of metastatic NSCLC., (© 2015 by American Society of Clinical Oncology.)

Background: Testing for EGFR mutations and ALK rearrangement has become standard in managing advanced nonsmall-cell lung cancer (NSCLC). However, many institutions in Europe, North America and other world regions continue to face a common challenge of facilitating timely molecular testing with rapid result turnaround time. We assessed the prevalence of biomarker testing for advanced NSCLC patients and whether testing affected the timeliness of treatment decisions., Methods: We conducted a retrospective chart review of a random sample of one-quarter of all patients with advanced NSCLC referred to the Princess Margaret Cancer Centre from 1 April 2010 to 31 March 2013., Results: Of 300 patients reviewed, 175 seen by medical oncology had nonsquamous NSCLC, 72% of whom had biomarker testing carried out. Patients tested for biomarkers were more likely to be female (47% versus 21%, P = 0.002), Asian (27% versus 6%, P = 0.005) and never smokers (42% versus 8%, P < 0.0001). Only 21% of patients with biomarker testing had results available at their initial oncology consultation. This group had a shorter median time from consultation to treatment decision (0 versus 22 days, P = 0.0008) and time to treatment start (16 versus 29, P = 0.004). Thirteen percent underwent repeat biopsy for molecular testing after the initial consultation. Of those with positive EGFR or ALK results, 19% started chemotherapy before biomarker results became available., Conclusions: Awaiting biomarker testing results can delay treatment decisions and treatment initiation for patients with advanced NSCLC. This may be avoided by incorporating reflex biomarker testing into diagnostic algorithms for NSCLC at the level of the pathologist, and further education of specialists involved in obtaining diagnostic cancer specimens to ensure they are sufficient for molecular testing., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The management of non-small cell lung cancer (NSCLC) has evolved into a multidisciplinary team approach that traditionally has involved medical oncology, radiation oncology, and thoracic surgery. However, in the era of personalized medicine the importance of molecular diagnostics requires adequate tissue for histologic subtyping and molecular testing and thus requires the engagement of other subspecialties such as pathology, respirology, and interventional radiology. Unfortunately in 2014, the majority of patients presenting with NSCLC will succumb to their disease and the early integration of palliative care into the treatment strategy will improve the quality of life and end-of-life care of our patients and may in fact improve their overall survival.

Background: Cetuximab-induced hypomagnesemia has been associated with improved clinical outcomes in advanced colorectal cancer (CRC). We explored this relationship from a randomized clinical trial of cetuximab plus best supportive care (BSC) versus BSC alone in patients with pretreated advanced CRC., Patients and Methods: Day 28 hypomagnesemia grade (0 versus ≥1) and percent reduction (<20% versus ≥20%) of Mg from baseline was correlated with outcome., Results: The median percentage Mg reduction at day 28 was 10% (-42.4% to 63.0%) for cetuximab (N = 260) versus 0% (-21.1% to 25%) for BSC (N = 251) [P < 0.0001]. Grade ≥1 hypomagnesemia and ≥20% reduction from baseline at day 28 were associated with worse overall survival (OS) [hazard ratio, HR 1.61 (95% CI 1.12-2.33), P = 0.01 and 2.08 (95% CI 1.32-3.29), P = 0.002, respectively] in multivariate analysis including grade of rash (0-1 versus 2+). Dyspnea (grade ≥3) was more common in patients with ≥20% versus < 20% Mg reduction (68% versus 45%; P = 0.02) and grade 3/4 anorexia were higher in patients with grade ≥1 hypomagnesemia (81% versus 63%; P = 0.02)., Conclusions: In contrast to prior reports, cetuximab-induced hypomagnesemia was associated with poor OS, even after adjustment for grade of rash.

An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4-ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc.

Introduction: GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase II dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC)., Patients and Methods: Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and >or=1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days., Results: Twenty-nine patients were treated, (24 NSCLC, 3 hormone-refractory prostate cancer, 1 head and neck, and 1 small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m(2) intravenously every 21days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase I, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D., Conclusions: Activity of the combination at RP2D, GTI-2040 5 mg/kg/d x 14 days by CVI plus docetaxel 75 mg/m(2) does not seem superior to docetaxel alone in previously treated NSCLC.

We developed a decision aid (DA) for patients with metastatic non-small cell lung cancer (NSCLC), to better inform patients of their prognosis and treatment options, and facilitate involvement in decision-making. In a pilot study, 20 patients with metastatic NSCLC attending outpatient clinics at a major cancer centre, who had already made a treatment decision, reviewed acceptability of the DA. The median age of the patients was 61 years (range 37-77 years), 35% were male, 20% had a university education, and most (75%) had English as a first language. Most had received chemotherapy, with 65% currently on treatment. Patients were not anxious at baseline and had clear understanding of the goals and toxicity of chemotherapy in advanced NSCLC. After reviewing the DA, patients' anxiety decreased slightly (P=0.04) and knowledge scores improved by 25% (P<0.001). Most improvements in understanding were of prognosis with and without chemotherapy, although patients still believed advanced NSCLC to be curable. Patients rated the DA highly with respect to information clarity, usefulness and were positive about its use in practice, although 40% found the prognostic information slightly upsetting. The DA for advanced NSCLC is feasible, acceptable to patients and improves understanding of advanced NSCLC without increasing patient anxiety.

Background: Tumor nodules are occasionally found in adjacent mesentery of colorectal cancer specimens and are felt to reflect a worse prognosis. The clinical significance of mesenteric tumor nodules was investigated., Methods: A review of 786 patients with stage III colorectal cancer referred between 1995 and 1999 was undertaken. TNM staging was standardized by considering mesenteric nodules separately and not assigning them to T or N categories. Survival analyses were performed., Results: Mesenteric tumor nodules were found in 116 (14.8%) patients: 48 (41.4%) with colon cancer and 68 (58.6%) rectal cancer. Mean age at surgery was 63 years. Adjuvant chemotherapy was given to 84.8% of colon cancer patients. Two (2.9%) rectal cancer patients received neoadjuvant chemoradiation, and 63 (92.6%) received adjuvant therapy (chemotherapy and/or radiation). In the cohort with mesenteric nodules, the median time to progression was 23.1 months, the median 5-year disease-free survival was 35%, and the median overall survival (OS) was 47.9 months, with 44% OS at 5 years. In the 19 (16.4%) patients with mesenteric nodules and no lymph nodes the 5-year OS was 60% (SEER stage II 5-year survival 82.5%), whereas in 97 patients who were lymph node-positive the 5-year OS was 40% (SEER 5-year survival stage IIIc 44.3%; stage IV 8.1%)., Conclusions: In comparison to SEER survival data, the presence of mesenteric nodules appears to worsen the prognosis of any T/N0 disease to that of overall stage III disease. Mesenteric nodules with any T/N+ disease had prognosis similar to that of stage IIIC disease, but the prognosis was better than M1 disease. ., (2007 American Cancer Society)

Background: Despite chemotherapy and radiotherapy for small cell lung cancer (SCLC), most patients die within 2 years. Response rates for second-line chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated liposomal formulation of doxorubicin, may be better tolerated and has activity in SCLC., Patients and Methods: Thirty-two patients were enrolled in a phase II study of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles., Results: Thirty patients were evaluable for response, with a response rate of 10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2 cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis, plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required transfusions. All patients on study have now expired, with a median survival of 28 weeks (7 months). For patients with SD or partial response, median time to progression was 15 weeks., Conclusion: The combination of Caelyx, cyclophosphamide and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest activity in relapsed SCLC with acceptable toxicity.

Background: Small bowel adenocarcinoma is a rare cancer that has generally been considered resistant to chemotherapy, although little has been published on the role of chemotherapy. A retrospective analysis was conducted of patients with advanced small bowel adenocarcinoma to explore chemotherapy use, and gain knowledge for ongoing management and future clinical trials., Patients and Methods: All patients with advanced adenocarcinoma of the small bowel treated at Princess Margaret Hospital (PMH) between 1986 and 2004 were identified through the cancer registry. The medical records were reviewed for patient characteristics, treatment and outcome data. Survival statistics were estimated using the Kaplan Meier survival curves and Cox proportional regression model., Results: Data on 113 patients was reviewed. Forty-four patients received palliative chemotherapy with an overall response rate (ORR) of 36% during a first or second line regimen (9% complete responses and 27% partial responses). Newer chemotherapy regimens including gemcitabine and irinotecan combinations appeared to have higher ORR, than older fluorouracil-based regimens. Some patients responded to more than one line of chemotherapy. Palliative chemotherapy predicted for overall survival (OS) in a multivariate analysis (HR 0.47, P = 0.035)., Conclusion: Chemotherapy appears to have activity in adenocarcinoma of the small bowel. Prospective trials evaluating patient benefit are required to confirm this activity using newer systemic therapies, until such time retrospective reviews such as this will continue to guide treatment decisions.

Purpose: This is a phase II study to assess the role of induction chemotherapy in the management of stage IIIA non-small-cell lung cancer (NSCLC). We are now reporting the long-term follow-up of the Toronto phase II trial., Methods: Sixty five patients with mediastinoscopy proven stage IIIA NSCLC received two cycles of preoperative MVP or VLB/P followed by thoracotomy followed by two further courses of chemotherapy., Results: The overall response rate was 67.7% with three complete and 41 partial responders. Forty seven patients went on to thoracotomy with 35 complete resections. Pathologically 4.6% of patients had no tumour remaining. There were three postop deaths as well as five chemotherapy related deaths. Of the 35 patients completely resected 19 have recurred including eight in brain. The median survival for the entire 65 patients is 18.6 months with a 1 year survival of 66%, 5 year survival of 29% and a 10 year survival of 22%., Conclusions: The long-term survival of induction chemotherapy is maintained. The high incidence of brain recurrences warrants assessment of the role of prophylactic cranial radiation. The role of surgery for stage IIIA NSCLC following induction chemotherapy awaits further study.

The purpose of this study was to determine the recommended phase II dose of liposomal doxorubicin (Caelyx ; Doxil in the United States) in combination with cyclophosphamide and vincristine for previously treated patients with good performance status with relapsed or refractory small-cell lung cancer. Twenty-one eligible patients were enrolled between November 1999 and September 2001 and received liposomal doxorubicin 25-40 mg/m2, cyclophosphamide 750-1000 mg/m2, and vincristine 1.2 mg/m2 intravenously (I.V.) every 21 days. At doses of liposomal doxorubicin 40 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V., 1 of 6 patients had dose-limiting neutropenia and fever in cycle 2 and 2 of 6 developed grade 3 hand-foot syndrome during cycle 3. Therefore, the recommended phase II doses are liposomal doxorubicin 35 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V. every 21 days. Antitumor activity was seen at all dose levels. This combination is well tolerated and has evidence of antitumor activity. A phase II evaluation is ongoing.

Purpose: To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non-small-cell lung cancer., Methods: A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada's public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data., Results: The incremental survival benefit in the docetaxel arm over BSC was 2 months (P =.047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m(2), the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of drugs, investigations, radiotherapy, and community care. BSC patients had fewer hospitalizations than patients in the chemotherapy arm and were more often palliated at home., Conclusion: Although the decision to treat should not be based on economic considerations alone, our CE estimate of $31,776 per year of life gained (at the currently recommended dose of docetaxel) is within an acceptable range of health care expenditures, and the total costs of therapy are similar to those of second-line palliative chemotherapy for other solid tumors.

Acute tumor lysis syndrome (ATLS) is a constellation of metabolic complications that typically occurs in the setting of treatment of hematologic malignancies. On occasion, it has been reported to occur after therapy for solid tumors associated with large tumor burdens and aggressive therapy. We herein report the occurrence of spontaneous acute tumor lysis syndrome in a man with untreated metastatic adenocarcinoma of the lung, and briefly discuss the literature.

Primary non-Hodgkin's lymphoma of bone (PLB) constitutes approximately 5% of all extranodal non-Hodgkin's lymphoma (NHL) and 7% of primary bone tumors. The peak incidence for PLB is in the fifth decade, with a slight preponderance of males over females. The presenting symptoms usually consist of localized bone pain and occasionally a palpable mass. Most patients with PLB have B-cell tumors with a diffuse mixed-cell or diffuse large cell histology. While most patients present with early-stage disease, it is not clear whether such patients benefit from combined-modality therapy (CMT) consisting of radiation therapy (RT) and chemotherapy (CT) compared with either RT or CT alone. However, there is strong evidence that CMT is beneficial in the treatment of localized NHL, and these results might be applicable to the therapy for PLB. Nevertheless, only a phase III randomized, controlled clinical trial will determine whether CMT is superior to either CT or RT alone.

Objective: To determine the prevalence of tearing and canalicular fibrosis in patients receiving systemic 5-fluorouracil (5-FU) therapy and the reversibility of the symptoms when treatment is stopped., Design: Prospective study., Setting: University-affiliated tertiary care hospital in Toronto., Patients: Thirty patients (17 men and 13 women aged 38 to 81 years) with advanced gastrointestinal carcinoma receiving intravenous 5-FU therapy as palliative (weekly) treatment (20 patients) or adjunctive (cycle) treatment (10 patients)., Outcome Measures: Tearing, eyelid changes and canalicular fibrosis during and after treatment. Patients who experienced tearing were advised to massage and wipe the lower eyelids in an upward direction., Results: Tearing and canalicular fibrosis developed in 10 patients (50%) and 3 patients (15%) respectively in the palliative treatment group; no patient in the adjunctive treatment group experienced these side effects. In the palliative treatment group, the patients who experienced tearing received double the dose of 5-FU (p = 0.03) and received treatment for twice as long (p = 0.042) as those who did not experience tearing. Of the patients with tearing, those in whom canalicular fibrosis developed received treatment for three times as long as those without fibrosis and received 2.6 times the total dose (p < 0.000). Of the seven patients with tearing in whom canalicular fibrosis did not develop, four stopped 5-FU treatment, and 2 to 4 weeks later the epiphora disappeared., Conclusions: Our findings suggest that the prevalence of tearing and canalicular fibrosis in patients receiving systemic 5-FU therapy as palliative treatment is related to the total dose and duration of treatment. Such side effects are less likely in those receiving adjunctive therapy. The epiphora is often reversible on stopping therapy if canalicular fibrosis has not yet developed.

Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle). All the 161 patients included were evaluable for toxicity and 151 of them were evaluable for efficacy. The majority of patients had a stage IIIb (31.1%) or stage IV (64.6%) disease; 10.6%, 83.2% and 6.2% of patients had a WHO performance status (PS) 0, 1, and 2, respectively. Adenocarcinoma accounted for 52.2% of cases and squamous cell carcinoma for 43.5% of cases. Three complete responses and 30 partial responses gave an objective response (OR) rate of 21.8% (95% confidence interval; 15.5-29.3%). All responses were validated by an independent Oncology Review Board. Median duration of response was 7.6 months. Median time to progression was 4.6 months (3.3 months in non responders and 7.6 months in responders). Median survival was 7.3 months in non responders and 13.4 months in responders (p < 0.001), which gave an overall median survival of 8.9 months (95% CI: 0.1-21.9 months) in the entire study population. An improvement of symptoms and personal state was also observed. Treatment was well tolerated. Neutropenia was the only dose limiting toxicity. WHO grade 3 or 4 neutropenia occurred in 19.6% and 5.7% of patients, respectively. With a 21.8% OR rate, this multicentre study confirms the activity of gemcitabine as a single agent in patients with inoperable NSCLC. Its good tolerance and original mode of action make gemcitabine a drug of choice in the therapeutic strategy of these tumors.

When given at doses of > or = 1,250 mg2 weekly x 3 with a 1-week break, single-agent gemcitabine induces responses in more than 20% of previously untreated patients with non-small cell lung cancer (NSCLC). This study was undertaken to determine the maximum tolerated doses for a 4-week cycle of gemcitabine and cisplatin given in combination weekly x 3 with a 1-week rest. Patients younger than 75 years were eligible if they had stage III/IV NSCLC, life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 2 x 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes < or = 3 times the upper limit of normal, and serum creatinine < or = 130 mumol/L. The starting doses for gemcitabine and cisplatin were 1,000 mg/m2 and 25 mg/m2 per week x 3, respectively. At dose level 2 cisplatin was increased to 30 mg/m2/week x 3. Thereafter only the gemcitabine was increased, by 250 mg/m2/wk at each dose level, to a maximum of 2,250 mg/m2/wk at dose level 7. The median nadir granulocyte and platelet counts decreased with each dose level, but dose-limiting toxicity in two or more patients was not encountered in the first treatment cycle, even at dose level 7. Cumulative bone marrow toxicity was seen at all dose levels, and this resulted in frequent dose reductions or omissions. Dose delivery was well maintained over time only at dose level 1. Grade 3-4 nonhematologic toxicity was infrequent and rarely dose limiting. An assessment of all toxicities seen during the treatment cycles was undertaken using continual reassessment methodology. This model suggested that dose level 4 (cisplatin 30 mg/m2/wk and gemcitabine 1,500 mg/m2/wk) would be the maximum dose at which grade 4 toxicity would be expected in up to 33% of patients at any time over four treatment cycles. Of 47 patients evaluable for response, partial remission was seen in 14, with an overall response rate of 30% (confidence interval, 17% to 43%). The median duration of response was 16 weeks and the median survival time was 24 weeks (range, 3.5 to 64+ weeks). A phase II trial is planned in which dose level 4 will be evaluated in a larger cohort of patients with NSCLC.

Gemcitabine is a novel nucleoside analogue with activity in solid tumours. This study assessed the objective response rate to gemcitabine given weekly intravenously at a dose of 1250 mg/m2 for 3 weeks followed by 1 week of rest (one cycle) in chemonaive patients with inoperable non-small cell lung cancer (NSCLC). 161 patients with NSCLC were recruited from 10 sites in nine countries. Most patients had stage IIIb (31.3%) or IV (64.6%) disease, and 93.8% had a performance status of 0 or 1 according to the WHO scale. Of 151 evaluable patients, there were 3 complete responses and 30 partial responses lasting at least 4 weeks for an objective response rate of 21.8% (95% CI 15.5-29.3%). All responses were validated by an extramural Oncology Review Board. The mean duration of response was 8.8 months. The mean survival for all patients (16.1% of patients still alive 26 months after last patient started treatment) was 11.5 months. Improvements were also observed in secondary efficacy parameters such as performance status, weight, analgesic requirement, pain, and other disease-related symptoms including cough, dyspnoea, haemoptysis, anorexia, somnolence and hoarseness. Haematological and non-haematological toxicity was mild given the biological activity of gemcitabine. This study confirms gemcitabine as one of the most active agents in NSCLC with the added benefit of a modest toxicity profile and ease of administration on an out-patient basis. Gemcitabine is a suitable candidate for combination chemotherapy in patients with NSCLC.

Gemcitabine is a nucleoside analogue with activity in non-small-cell lung cancer (NSCLC). Phase I trials have determined the best tolerated dose of gemcitabine in chemotherapy-naive patients to be 1250 mg/m2 given as a 30-minute infusion weekly x 3 every 4 weeks. The single-agent efficacy of gemcitabine has been assessed in 4 phase II trials (361 patients) at dose of 800-1250 mg/m2/weekly x 3 every 4 weeks. Single-agent response rates (externally verified by Oncology Review Board) were > 20%, with duration of response 7.6-12.7 months and median survival 8-9 months. Dose-limiting toxicity was neutropenia, but this was rare, even at the highest dose levels. In 3 Japanese studies, response rates of 16.3%, 26% and 20.9% were seen in untreated patients. Pooled data from all NSCLC studies shows that responses were seen in stages IIIA, IIIB and IV disease, and were similar in adeno and squamous cell types. Gemcitabine has also been studied in combination with other drugs active in NSCLC. In one study 50 patients were treated with gemcitabine and cisplatin given weekly x 3 every 4 weeks, cisplatin at a dosage of 25-30 mg/m2 and gemcitabine at doses escalating from 1000 mg/m2 in steps of 250 mg/m2 per cycle, 38 of 50 patients have been evaluated to date, with an overall response rate of 31.6%. Dose limiting toxicity was rare, but there was evidence of cumulative haematological toxicity with grade 4 granulocytopenia and thrombocytopenia becoming more frequent with repeated administration. Similar activity was seen when gemcitabine (1000 mg/m2) was combined with monthly cisplatin (60, 75, 100 mg/m2). Other studies have shown that gemcitabine can enhance radiosensitivity in NSCLC and other solid tumour types such as pancreas/breast and colorectal cancer cell lines.

The incidence of mediastinal tumors is increasing throughout North America. The benign variants are usually managed by relatively simple surgical procedures. Malignant mediastinal tumors can be among the most challenging of medical and surgical conditions and may require the expertise of medical, radiation, and surgical oncologists. Thymomas, germ-cell tumors, and lymphomas comprise the majority of the malignant mediastinal neoplasms. Some variants are managed entirely medically while others are extirpated initially. Many require multimodality therapies, either according to an accepted protocol or, more challengingly, off protocol.

Background: This study relates our experience in the diagnosis and treatment of a rare clinical entity, non-Hodgkin's primary lymphoma of bone., Methods: Seventeen cases of patients with primary lymphoma of bone diagnosed and treated at a single institution between 1975 and 1992 are reviewed. Ten patients received combined-modality therapy, consisting of an anthracycline-containing combination chemotherapy (CT) regimen, followed by adjuvant radiotherapy (RT) to the primary site of disease. Five patients were treated with CT alone; one patient received RT alone; and one patient was treated with CT after emergency RT for spinal cord compression., Results: Thirteen patients presented with Stage I disease, two with Stage II; and two with Stage IV disease (multiple bony sites only). Thirteen patients had an intermediate-grade diffuse large cell lymphoma; two had an intermediate-grade mixed small and large cell lymphoma; and two had a high-grade lymphoma (one immunoblastic and one small non-cleaved cell lymphoma). The overall response rate was 94% (18% complete response, 58% partial response 1, and 18% partial response 2). Thirteen patients are alive and disease-free at a median of 29 months; 10 of these received CT+RT, and 3 received CT alone. Three patients have died; one of these received CT+RT and one CT alone, and one relapsed immediately after CT. One patient, who was initially treated with RT and then with CT+RT after relapse, was lost to follow-up 40 months from the start of treatment., Conclusions: Because experience in the literature suggests a 50% distant relapse rate in primary lymphoma of bone treated with RT alone, our policy is to treat all patients with combined-modality therapy (CT+RT). However, only a Phase III randomized, controlled clinical trial will determine whether CT+RT is superior to either modality alone.

Objective: To evaluate the diagnosis and management of patients with malignant lymphoma of bone., Design: A case series review in which the minimum follow-up was 24 months and the mean follow-up was 49 months., Setting: All patients were managed at a tertiary care centre, although initial biopsies were often done in community centres., Patients: Selected for review were 15 of 18 consecutive patients who were referred to the Musculoskeletal Oncology Unit at the Mount Sinai Hospital, Toronto, between 1984 and 1989, with a bone lesion as the presenting symptom of lymphoma. The three excluded patients included two with diffuse nodal disease at presentation and one who had a second, unrelated malignant tumour., Interventions: Staging studies (hematologic investigations, radiography, technetium bone scanning and computed tomography), surgical biopsies of the lesion, chemotherapy, radiotherapy and in some cases surgical resection of the lesion., Main Outcome Measures: The number of biopsies required for diagnosis and the incidence of complications that required operative intervention., Results: Seven of the 15 patients required more than one biopsy to establish the diagnosis. Five patients required surgical procedures for late complications that included pathologic fractures, wound infection and osteonecrosis. At 24 months' follow-up, 13 patients were disease free and 2 had died., Conclusions: Proper biopsy and pathological evaluation are crucial in the diagnosis of lymphoma of bone. These measures will decrease the necessity for repeat biopsies. Lymphoma is best managed medically. Surgery should be reserved for biopsy and for treatment of the complications of therapy.

Thirty-nine patients with mediastinoscopy stage IIIA, N2 non-small cell lung cancer received two cycles of MVP (mitomycin C, vindesine, cisplatin). Responders underwent thoracotomy for resection and two further courses of MVP. Overall response rate was 64% (25/39) with three complete and 22 partial responses. Twenty-two patients were resected, which included radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no remaining tumor. Toxicity included two postoperative deaths with B-P fistula, mitomycin pulmonary toxicity in two patients, and four septic deaths. Twenty-eight patients have died, 20 with recurrent or progressive disease. Of the 18 patients completely resected, eight have recurred with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain) and one in both. Median survival of the entire 39 patients is 18.6 months, with a three year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%.

Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.

Purpose: The 5-year survival rates with surgical resection for preoperatively identified stage IIIA N2 non-small-cell lung cancer (NSCLC) are less than 10%. A pilot study of mitomycin, vindesine, and cisplatin (MVP) induction chemotherapy was undertaken in an attempt to improve the curative potential of surgery in this group of patients., Patients and Methods: Thirty-nine patients with mediastinoscopy stage IIIA N2 NSCLC received two cycles of MVP. Responding patients underwent thoracotomy for resection and two further courses of MVP., Results: The overall response rate was 64% (25 of 39) with three complete and 22 partial responses. Twenty-two patients were resected, which included a radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no tumor remaining. Toxicity included two postoperative deaths secondary to a bronchopleural (BP) fistula, mitomycin pulmonary toxicity in two patients, and septic deaths in four patients. Twenty-eight patients have died; 20 have recurrent or progressive disease. Eight of the 18 patients completely resected have recurred, with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain), and one in both. Median survival of all 39 patients is 18.6 months, with a 3-year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%., Conclusions: We conclude (1) that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC; (2) the median survival seems to be prolonged; and (3) the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a phase III randomized trial to compare it with other treatment modalities.

Twenty-six patients with poor-risk Kaposi's sarcoma and AIDS were treated with epirubicin 90 mg/m2 intravenously every 3 weeks. One patient achieved complete response and 10 achieved partial response (overall response rate 42.3%). The median time to treatment failure was 22 weeks. The dose-limiting toxicity was neutropenia.

We describe the histologic and clinical features of non-Hodgkin's lymphoma diagnosed between January 1980 and December 1983 in 90 homosexual men from San Francisco, Los Angeles, Houston, and New York. The median age was 37 years, with an age distribution identical to that for cases of AIDS reported to the Centers for Disease Control. Sixty-two per cent of the patients had high-grade (aggressive) subtypes of lymphoma, 29 per cent had subtypes of intermediate grade, and 7 per cent had low-grade subtypes. Histologic subtypes and malignant cell phenotypes were consistent with a B-cell origin. All but two men had extranodal lymphoma: central-nervous-system, bone-marrow, bowel, and mucocutaneous sites were most commonly involved. Thirty-five of 66 evaluable men (53 per cent) had complete responses to combination chemotherapy or radiotherapy or both, and thus far, 19 (54 per cent) of them have had a relapse. Mortality and morbidity were closely related to prodromal manifestations; death or illness have occurred in 19 (91 per cent) of the 21 men who presented with AIDS, in 26 (79 per cent) of the 33 who presented with generalized lymphadenopathy, and in 5 (42 per cent) of the 12 who had no prodromal manifestations. Mortality rates analyzed according to histologic grade were higher than currently reported rates in other patient populations. Kaposi's sarcoma or severe opportunistic infections characteristic of AIDS developed in 14 of 33 men (42 per cent) who presented with generalized lymphadenopathy and in 3 of 12 (33 per cent) without prodromal manifestations. We conclude that non-Hodgkin's lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and the AIDS-related complex.

Lymphoma of the rectum is a rare tumor and in most studies is not separated from other lymphomas of the large intestine. We have recently examined four homosexual men with lymphoma presenting in the rectum. Symptoms included rectal bleeding in three, pain on defecation in two, and mucoid rectal discharge in two. Systemic "B" symptoms (ie, fever, night sweats, and/or weight loss), as well as a rectal mass, were present in all four. All were high-grade tumors, with B-cell immunoblastic sarcoma in two and small noncleaved Burkitt-like lymphoma in two. Intracytoplasmic immunoperoxidase staining revealed monoclonal kappa light chains in three tumors, whereas the fourth was nonstaining. Immunologic abnormalities were similar to those reported in patients with acquired immunodeficiency syndrome. Antibodies to human T-cell lymphotropic virus type III were found in the three cases tested, and retrovirus was cultured from lymphomatous tissue in one. Despite multiagent chemotherapy, two patients died within six months of diagnosis and a third has recently suffered relapse within the central nervous system.

Opportunistic infections and malignant neoplasms have been described in homosexual men in association with immunologic abnormalities. We observed the development of malignant B-cell lymphomas in two homosexual men who had had a monogamous relationship for two years. Patient 1 had an aggressive, monoclonal, small, noncleaved, non-Burkitt's lymphoma ("undifferentiated lymphoma"), associated with severe immunocompromise. Patient 2 manifested a monoclonal, small, cleaved, follicular center cell lymphoma, with a follicular pattern, two months later. No common acute infection was detected. Staining for Epstein-Barr nuclear antigen in malignant tissue was negative in the second patient. However, the possibility of a transmissible agent as a causative factor cannot be excluded, and further study of similar patients is warranted.

Persistent, generalized lymphadenopathy (PGL) is considered part of the acquired immunodeficiency syndrome (AIDS)-related complex. The clinical course is usually benign, although some patients may evolve to AIDS. Characteristic features on lymph node biopsy have been described. Recently, large series of PGL have been reported in which many study patients have not undergone initial diagnostic biopsy. The value of such biopsy has been questioned. We report the clinical, pathologic, and laboratory findings in six homosexual men initially considered as potential candidates for study of the natural history of PGL. They were excluded by initial lymph node biopsy, which revealed small-cleaved lymphoma in two, focal Kaposi's sarcoma in two, disseminated mycobacterium tuberculosis in one, and histoplasma encapsulatum in one. The clinical and laboratory data from these six patients were compared with those from 34 patients with biopsy-proven PGL; no statistically significant difference in any prebiopsy clinical parameter was found. We conclude that initial lymph node biopsy may reveal changes other than reactive hyperplasia in homosexual men with generalized lymphadenopathy.

Primary central nervous system lymphoma constitutes one of the criteria for the acquired immune deficiency syndrome (AIDS), yet a paucity of information is currently available regarding the clinical, immunologic, or pathologic features of these patients. Six homosexual men presenting with primary central nervous system lymphoma were evaluated. Five of these patients presented with altered mental status. All lymphomas were intracranial. B cell immunoblastic sarcoma was found in five. Immune phenotyping studies performed in five patients revealed monoclonal lambda light chain in three, whereas one expressed only IgG heavy chain, and one demonstrated another B cell (LN-1) surface antigen. Hypodense, contrast-enhancing lesions were apparent on computed axial tomographic scanning of the brain, in sharp contrast to isodense or hyperdense lesions reported in primary central nervous system lymphomas without underlying immunodeficiency. Immunologic abnormalities in these patients were similar to those in AIDS presenting as Kaposi's sarcoma or with opportunistic infections. In spite of therapeutic interventions, survival was short, and only one patient is currently alive.

Low serum cobalamin levels in 10 patients with AIDS or AIDS-related complex led us to also prospectively survey 40 homosexual men in our AIDS clinic. 8 of the latter (20%) had low cobalamin values. We found no evidence of megaloblastic changes in the blood or bone marrow. Assessment disclosed malabsorption of cobalamin in only 1 of 6 cases tested for it. 6 of the patients were treated with cobalamin and had no hematologic response. It appears that low serum cobalamin levels in AIDS and related disorders do not usually represent overt cobalamin deficiency. While malabsorption is occasionally responsible for the low cobalamin level, in most cases the cause is unknown and may reflect a serum abnormality similar to that in multiple myeloma. AIDS and related disorders should be considered in the differential diagnosis of unexplained low cobalamin levels.

In order to investigate the nature of the immune disorders associated with the acquired immune deficiency syndrome (AIDS) and the AIDS-related condition of persistent, generalized lymphadenopathy (PGL), serum beta-2 microglobulin (beta 2-M) levels were determined in patients with AIDS and PGL and in asymptomatic homosexual and heterosexual controls. Sixteen of 20 (80%) patients with AIDS exhibited elevated beta 2-M levels. In contrast, 20 of 44 (45%) patients with PGL, 4 of 20 (20%) asymptomatic homosexuals, and only 3 of 46 (7%) heterosexuals had increased serum beta 2-M levels (P less than 0.001). When considering mean levels of beta 2-M, only the asymptomatic control individuals had normal values. AIDS patients had significantly higher mean beta 2-M levels when compared to all other groups (P less than 0.05). The mean level for PGL patients was greater than that in the homosexual and heterosexual controls (P less than 0.05). No relationship was found between presence of antibody to human T-lymphotropic retrovirus (HTLV-III) and beta 2-M levels in the patients with AIDS or PGL. The authors conclude that beta 2-M is elevated in patients with AIDS and PGL, suggesting an increased turnover of a certain subpopulation of lymphocytes in these patients. Beta 2-M levels also appear to parallel disease activity, as well as immune dysfunction, with the greatest elevation occurring in patients with AIDS, followed by those with PGL, and asymptomatic homosexuals. Beta 2-M levels may be a useful confirmatory marker in AIDS and its related disorders.

We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.

The most common manifestations of the acquired immunodeficiency syndrome include Pneumocystis carinii pneumonia and/or Kaposi's sarcoma. High-grade B-cell lymphomas have also been reported in homosexual men at risk for the acquired immunodeficiency syndrome. We herein present the case of a homosexual man, who presented simultaneously with Pneumocystis carinii pneumonia, acute cytomegalovirus infection, Kaposi's sarcoma, and B-cell immunoblastic sarcoma. Severe compromise of both the B- and T-cell arms of the immune system was documented. The patient had evidence of exposure to the human T-lymphotropic retrovirus III, evidence of reactivation of Epstein-Barr virus infection, and cytomegalovirus inclusions within Kaposi's sarcoma tissue. We conclude that exposure to these viral agents in the setting of severe immunocompromise may have led to the observed "opportunistic" neoplasms.

A syndrome of persistent, generalized lymphadenopathy (PGL), related to the acquired immune deficiency syndrome (AIDS), has been described in homosexual men. To further characterize and correlate the immunologic status of patients with PGL with those in AIDS, we studied spontaneous and pokeweed mitogen (PWM)-induced IgG synthesis by B-cells, T-cell subsets in peripheral blood (PB), natural cytotoxicity (NC), and Interleukins (IL)-1 and IL-2 production in 39 homosexual patients (21 PGL; 13 AIDS; five asymptomatic homosexual men), in whom 32 of 35 tested (91%) had antibodies to human T-lymphotropic virus-III (HTLV-III). A profound abnormality in B-cell function was found in AIDS and PGL, consisting of high spontaneous IgG production, with paradoxic suppression of IgG synthesis after PWM. IL-2 values were more often low in AIDS when compared with PGL (P less than 0.001). The PB lymphocyte count was normal in PGL and reduced in AIDS (P less than 0.001). OKT4 "helper" cells were decreased in PGL, but even lower in AIDS (P less than 0.001), while OKT8 "cytotoxic/suppressor" cells were normal in AIDS and increased in PGL (P less than 0.01). The T4:T8 ratio was reversed in both, but more abnormal in AIDS (P less than 0.001). A decrease in NC killing was observed in AIDS when compared with heterosexual controls. Thus, patients with PGL and AIDS both demonstrate a spectrum of immunologic dysfunction, involving the cellular and humoral arms of the immune system.