Causes of death among cancer patients.

Background: The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. Patients and methods: US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. Results: The greatest relative decrease in index-cancer death (generally from > 60% to < 30%) was among those with cancers of the testis, kidney, bladder, endometrium, breast, cervix, prostate, ovary, anus, colorectum, melanoma, and lymphoma. Index-cancer deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among <50-year olds (e.g. SMR >1,000 for lymphomas, P < 0.001). The highest SMRs were typically within the first year after cancer diagnosis (SMRs 10-10,000, P < 0.001). Prostate cancer patients had increasing SMRs from Alzheimer's disease, as did testicular patients from suicide. Conclusion: The risk of death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis.

Survival after HLA-identical allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials.

The impact of peripheral blood stem cell transplantation (PBSCT) on survival relative to bone marrow transplantation (BMT) remains poorly defined. Several randomized controlled trials (RCTs) comparing HLA-matched related PBSC- and BMT for patients with hematologic malignancies have been published, yielding differing results. We conducted a meta-analysis of published RCTs to more precisely estimate the effect of PBSCT on survival. Seven trials that assessed survival were identified and included in our analysis. Using a fixed effects model, and combining the results of all seven trials, the summary odds ratio for mortality after PBSCT was 0.81 (95% CI, 0.62-1.05) when compared to BMT. Subgroup analysis revealed no association between the median PBSCT 34+ cell dose and relative risk for morality after PBSCT. However, there was an association between the proportion of patients enrolled with advanced-stage disease and the summary odds ratio for mortality. The pooled estimate was 0.64 for studies where patients with intermediate/advanced disease comprised at least 25% of enrollment, and was 1.07 for the studies enrolling a smaller proportion. This finding substantiates results from previously published studies that have demonstrated a survival advantage with PBSCT limited to patients with advanced disease.

A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population.

BACKGROUND: A prospective multi-institutional phase II trial was undertaken to define the activity and toxicity of a unique decrescendo infusion of interleukin-2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal cell carcinoma. The identical regimen has shown promise in advanced melanoma. PATIENTS AND METHODS: Between February 1997 and March 1999, 47 patients with metastatic renal cell carcinoma, from five institutions, were treated with outpatient s.c. IFN (10 mU/m2/day) on days 1-5, followed by inpatient IL-2 via continuous i.v. decrescendo infusion [18 million International Units (MIU) (I mg)/m2/6 h, followed by 18 MIU/m2/12 h, then 18 MIU/m2/24 h and 4.5 MIU/m2/24 h for the following 3 days] on days 8-12, in a hospital ward without intensive care unit (ICU)-type monitoring. Treatment was repeated every 4 weeks. In contrast to high dose IL-2 protocols, patient eligibility did not require pulmonary function tests and allowed serum creatinine up to 2 mg/dl. RESULTS: Among 44 eligible patients, 57% (25) had their primary in place, 57% (25) had bone or visceral involvement, and only 4% (2) had lung as their only site of disease. The overall response rate in 43 response-evaluable patients was 16.3% [95% confidence interval (CI) 5.3 to 27.3], with three complete responses and four partial responses observed. The median survival was 13 months; nine patients remain alive at >23 months. The median duration of response is 36 months (range 11.5 to 48+ months). Toxicity was modest, consisting of typical cytokine-induced systemic symptoms and rare organ dysfunction. Severe grade 4 toxicity occurred in only 13% of the 130 cycles. CONCLUSIONS: This unique, reasonably well tolerated IL-2/IFN combination induced a modest response rate with a number of durable remissions. While the optimal IL-2-based regimen for the treatment of advanced renal cell carcinoma remains elusive, the present regimen should attract considerable interest. This is based on tumor activity very similar to high dose IL-2 in a patient population not as carefully selected for optimal organ function.

Outpatient care and morbidity reduction in diabetic foot ulcers associated with chronic pressure callus.

In a retrospective review of 233 cases of diabetic foot ulceration preceded by minor trauma, 192 ulcerations exhibited focal pressure keratosis as the preceding traumatic event. The frequency of outpatient visits and other foot care interventions were correlated with the occurrence and severity of ulceration. Patients seen more frequently in an outpatient foot clinic had less severe ulcers and were less likely to undergo surgical treatment than those with less frequent visits.

A murine model for the effects of pelvic radiation and cisplatin chemotherapy on human papillomavirus vaccine efficacy.

Therapeutic human papillomavirus (HPV) vaccines for cervical cancer depend on a competent immune system to be effective. However, cancer patients are often found to be immunosuppressed, which could be attributable to prior radiation, chemotherapy, or the tumor burden itself. This study investigated whether pelvic radiation or cisplatin treatment affected the efficacy of an HPV vaccine and how long these effects lasted. Mice were given pelvic radiation, 2 Gy/day to a total dose of 45 Gy, or 5 mg/kg/week of cisplatin for 3 weeks. Mice were then immunized with an HPV-16 peptide vaccine between 0 and 16 weeks after their treatment. An ELISPOT analysis revealed that a reduced level of peptide-specific, IFNgamma-producing spleen cells was present in immunized mice treated previously with pelvic radiation or cisplatin compared with immunized mice that had not been treated. However, when mice were challenged with HPV-16-expressing tumor cells, immunized mice developed no tumors, regardless of prior treatment, whereas nonimmunized mice did develop tumors. Our results suggest that pretreatment with pelvic radiation or cisplatin alone does not prevent the induction of an effective immune response by a peptide vaccine. These data will have important implications for immunotherapeutic treatment of pretreated cancer patients, especially in the adjuvant setting when immunosuppression by tumor burden would be low.

Double-blind comparative trial of oral ondansetron versus oral granisetron versus IV ondansetron in the prevention of nausea and vomiting associated with highly emetogenic preparative regimens prior to stem cell transplantation.

The optimal management of transplantation preparative regimen-induced nausea and vomiting remains unknown. We conducted a Phase III double-blind study to determine the efficacy and costs of oral ondansetron versus oral granisetron versus IV ondansetron and PRN rescue antiemetics for the prevention/control of nausea and vomiting associated with high-dose chemotherapy or chemoradiotherapy prior to stem cell transplantation. One hundred two patients were randomized to receive either 8 mg PO ondansetron every 8 hours, 1 mg PO granisetron every 12 hours, or 32 mg IV ondansetron every 24 hours plus 10 mg IV dexamethasone daily during and 1 day after the various preparative regimens. Study arms were compared in terms of emetic episodes, subjective nausea, amount and cost of rescue antiemetics used, and total costs. Response was defined as complete response (CR), no emesis with no or mild nausea and no rescue antiemetics; major response (MR), 1 episode of emesis or moderate nausea with or without rescue antiemetics; and major efficacy (ME), CR + MR. Subjective nausea was assessed using a 100-mm visual analog scale (VAS) with 0 = no nausea. Ninety-six patients completed the study; the trial was analyzed according to intention-to-treat. Overall CR rates were: 48% for oral ondansetron, 47% for oral granisetron, and 49% for IV ondansetron. Overall ME rates were 82% for oral ondansetron, 84% for oral granisetron, and 81% for IV ondansetron. Mean VAS scores were 32 for oral ondansetron, 32 for oral granisetron, and 27 for IV ondansetron. None of the differences were statistically significant. A cost analysis revealed significant differences among all arms (P = .0001, all comparisons). All 3 regimens had similar efficacy in this BMT population; oral ondansetron was the most cost-effective.

Recurrent basal cell carcinoma after incomplete resection.

BACKGROUND: Because the probability of basal cell carcinoma (BCC) recurrence was thought to be 30% to 50%, surgical tradition became not to perform additional resection when the margin was positive. OBJECTIVE: To determine whether there is an association among age or sex of the patient, anatomic location, histologic type, or reconstructive procedures and the signs and symptoms of the recurrence, interval between incomplete resection and Mohs micrographic surgery (MMS), or extent of MMS resection. DESIGN: During 20 years, all patients with incompletely excised BCC of the head referred for MMS were sequentially prospectively accrued into the cohort. SETTING: An outpatient MMS practice. PATIENTS: Nine hundred ninety-four patients. MAIN OUTCOME MEASURES: Interval to tumor recurrence, interval to MMS, and extent of MMS as determined by mean surface area resected, depth of resection, and number of tumor nests. RESULTS: The interval to signs or symptoms of recurrence and to MMS from incomplete resection was greater for men, patients older than 65 years, those having a tumor on the nose or cheek, those with aggressive or fibrosing BCC, and those who underwent flap reconstruction (P =.001). The extent of MMS resection was greater for those with flap and split-thickness skin graft repairs. The number of tumor nests identified by MMS was significantly greater in those treated with split-thickness skin graft and flap (P =.001). CONCLUSION: Because it is more difficult to control recurrent BCC, treating tumor remaining at the margin of resection in the immediate postoperative period could result in less extensive surgery.

Identification of new minimally lost regions on 18q in head and neck squamous cell carcinoma.

Loss of heterozygosity (LOH) on 18q predicts poor survival in head and neck squamous cell carcinomas (HNSCCs). Several putative tumor suppressor genes, such as DCC, DPC4/Smad4, and MADR2/Smad2, are mapped to 18q, but thus far, the important gene locus in HNSCC is not known. To identify possible gene loci on 18q, we performed LOH studies using tumor DNA from 57 HNSCC primary tumor cell lines and DNA isolated from fibroblasts or lymphoblastoid cells from the same patients. Forty-two highly polymorphic microsatellite markers spaced not more than 5 cM apart (mean distance, 1.82 cM) spanning the region from D18S44 in 18q11.1 to D18S1141 in 18q23 were used. D18S71 in 18p11.21 on 18p was also used to determine whether the short arm was retained. Forty-three of 57 (75%) HNSCC lines showed LOH or isolated allelic imbalance (AI) for at least one locus on 18q. Although many of the cell lines had large distal 18q deletions with a breakpoint between 18q11.1 and 18q12.2 to qter, three loci were identified that were lost in 70% or more of the cases. The minimally lost regions (MLRs) range in size from 1.5-15.79 cM. The most proximal is centered on D18S39 (1.56 cM) in band 18q21.1, with LOH or isolated AI in 28 of 38 (74%) of informative cases. The largest (15.8 cM) begins at D18S61 (28 of 40; 70%) in band 18q22.2 and extends through D18S50 in 18q23. The third is centered on D18S70 (30 of 40; 75%) in band 18q23 (3.67 cM). Of these MLRs, only the one centered on D18S39 has been implicated previously in HNSCC. D18S70, the most frequently lost marker, was the only marker consistently lost in three tumor cell lines with very minimal losses, UM-SCC-19, UM-SCC-67, and UM-SCC-73A. In addition, UM-SCC-91 exhibited AI only at this locus, and UT-SCC-4 had AI at D18S70 and D18S39 only. Close physical mapping of these three regions may pinpoint one or more previously unidentified tumor suppressor genes.

How well do third-year medical students learn key objectives in a case-based surgical lecture series?

Faculty members were asked to list major and minor concepts of their case-based session presented during the 12-week 3rd-year surgical clerkship. After each session, students were queried to list the key concepts presented. Data were collected from two groups: one at the end of an academic year and a second at the beginning of the next academic year. Faculty members listed a median of 10 major and 15 minor concepts. The mean number of matched major concepts ranged from 0.2 to 4, and from 0.2 to 3.4 for minor concepts. In a comparative analysis, the end-of-the-year students listed a higher number of matched concepts for 17 of the 20 sessions than the beginning of the year students (8 sessions reached statistical significance, P < 0.05). The current case-based teaching method is not effective in emphasizing key concepts to students. Reformatting cases to better align with key concepts may be one solution to enhance a student's ability to grasp key concepts. Students at the end of the academic year outperformed those at the beginning of the year. This additional variable needs to be considered by faculty and incorporated into their teaching techniques.

P53 overexpression is associated with bulky tumor and poor local control in T1 glottic cancer.

PURPOSE: To study the role of two possible prognostic factors, p53 and tumor bulk, and their interaction with other tumor and treatment variables in early-stage laryngeal cancer patients treated with curative radiotherapy. METHODS: One hundred two patients with T1N0M0 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy were analyzed. p53 status in pretreatment biopsy specimens was assessed by immunohistochemistry (IHC) using mouse monoclonal antibody DO-7. Tumors were classified as small surface lesions or bulky tumors. All tumor-related and treatment-related variables which might influence the outcome were analyzed. Local control after definitive radiotherapy was the end point of the study. RESULTS: The local control at 5 years for the entire group of patients was 78% (80/102) and 91% (93/102) after surgical salvage. p53 overexpression by IHC was seen in 37% (38/102) of patients. Tumors were classified as small volume in 69 (68%) and bulky in 33 (32%) patients. Five-year local control was 48% for p53-positive patients as compared to 94% for p53-negative patients (p = 0.0001). Tumor bulk was the other important prognostic factor, with 5-year local control of 91% for small tumors and 48% for bulky tumors (p = 0.0001). Patients who had both p53 positivity and bulky tumors did worse, with a 5-year local control of 23% as compared to 92% for all other groups combined (p = 0.0001). Among other variables, only the length of radiation time was of borderline significance. CONCLUSION: Both p53 overexpression and tumor bulk are independent prognostic factors for local control in early-stage glottic cancer treated with curative radiotherapy. The precise relationship between a genetic event, the p53 mutation, and an observable phenotype expression such as tumor bulk needs to be further defined.

Changes in thyroid nodule volume caused by fine-needle aspiration: a factor complicating the interpretation of the effect of thyrotropin suppression on nodule size.

The effectiveness of TSH suppression therapy for thyroid nodules remains controversial. Prior studies have assumed that the fine-needle aspiration biopsy (FNAB), used to confirm a benign condition before the establishment of control and treatment groups, has no effect on nodule volume. Seventeen untreated euthyroid patients with clinical solitary thyroid nodules that were solid (on high-resolution ultrasound) and a colloid goiter (on cytologic examination) had ultrasound measurements of nodule volume before a FNAB, immediately thereafter, and 1 month and 6 months later. Size differences and individual variability at each time period were analyzed. No significant difference in mean thyroid nodule volume was present at any point after the FNAB; however, the changes in nodule volume were quite marked and bidirectional among patients masking the cumulative effect. The variability of the change in individual nodule volume was statistically significant when comparisons were made across time (P = 0.0032). FNAB of thyroid nodules results in significant individual changes in volume after the procedure. Studies, such as the effect of TSH suppression on thyroid nodule volume, that incorporate the FNAB in both control and treatment arms of the experimental design, need to take these changes into account, less erroneous conclusions result.

Predictive markers for response to chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma.

OBJECTIVE: A systematic retrospective study of the largest randomized trial of induction chemotherapy and radiation for advanced laryngeal cancer was undertaken to determine whether specific tumor or biologic factors were predictive of chemotherapy response, organ preservation, or survival. METHODS: The variables analyzed included clinical and histologic factors, immunohistochemical expression of proliferating cell nuclear antigen and p53, and adjusted DNA index measurements. Variables were evaluated for correlation with outcomes of tumor response, organ preservation, and survival. RESULTS: Multivariate analysis revealed that the best predictor of complete response to induction chemotherapy was low T class. The full multivariate model for predicting larynx preservation in patients treated with induction chemotherapy plus radiation shows that T class, p53 overexpression, and elevated proliferating cell nuclear antigen index were independent predictors of successful organ preservation. CONCLUSIONS: These predictive markers should be included in future clinical trials of advanced laryngeal cancer to determine their usefulness prospectively.

Higher prevalence of abdominal aortic aneurysms in patients with carotid stenosis but without diabetes.

BACKGROUND: We compared abdominal aortic aneurysm (AAA) prevalence in 3 groups of patients at the Hines Veterans Affairs Medical Center: (1) patients with 50% or more carotid stenosis, (2) patients with less than 50% stenosis, and (3) patients screened for the Aneurysm Detection and Management (ADAM) study. METHODS: Of all the patients referred to the vascular laboratory for carotid duplex examination during a 12-month period, patients with 50% or more carotid stenosis underwent ultrasonography of the abdominal aorta unless they had a previous scan or previous aortic surgery (group 1, n = 374). Patients with less than 50% carotid stenosis who had been screened for ADAM comprised group 2 (n = 139). They were compared with all patients screened for ADAM at our center during the same time period (group 3, n = 2477). RESULTS: AAA of 3.0 cm or more were present in 18.2%, 12.2%, and 7.2% of groups 1, 2, and 3, respectively; AAA of 4.0 cm or more were present in 8.3%, 5.8%, and 2.1% of groups 1, 2, and 3, respectively. Among patients with carotid stenosis, those patients without diabetes accounted for the observed increase in prevalence (21.9 % > or = 3.0 cm and 10.2% > or = 4.0 cm vs 9.2% and 2.8% in patients with diabetes). CONCLUSIONS: The relative risk of AAA is 2 to 3 times greater in patients with carotid stenosis compared with patients undergoing routine screening. However, only patients without diabetes account for the increased prevalence. Selective AAA screening of patients who are not diabetic with carotid stenosis is recommended.

Cancer risk associated with simian virus 40 contaminated polio vaccine.

BACKGROUND: The presence of SV40 in monkey cell cultures used in the preparation of the polio vaccine from 1955 through 1961 is well documented. Investigations have consistently demonstrated the oncogenic behavior of SV40 in animal models. Early epidemiologic studies were inadequate in demonstrating an increase in cancer incidence associated with contaminated vaccine. Recently, investigators have provided persuasive evidence that SV40 is present in human ependymomas, choroid plexus tumors, bone tumors, and mesotheliomas, however, the etiologic role of the virus in tumorigenesis has not been established. MATERIALS AND METHODS: Using data from SEER, we analyzed the incidence of brain tumors, bone tumors, and mesotheliomas from 1973-1993 and the possible relationship of these tumors with the administration of the SV40 contaminated vaccine. RESULTS: Our analysis indicates increased rates of ependymomas (37%), osteogenic sarcomas (26%), other bone tumors (34%) and mesothelioma (90%) among those in the exposed as compared to the unexposed birth cohort. CONCLUSIONS: These data suggest that there may be an increased incidence of certain cancers among the 98 million persons exposed to contaminated polio vaccine in the U.S.; further investigations are clearly justified.

Effects of amiodarone on tumor necrosis factor-alpha levels in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of congestive heart failure and may be associated with an increase in mortality. A recent in vitro study showed that amiodarone decreases TNF-alpha production by human blood mononuclear cells in response to lipopolysaccharide. However, no previous clinical studies have determined the effect of chronic amiodarone therapy on TNF-alpha levels. Thus, the purpose of this study was to determine whether amiodarone affects TNF-alpha levels in patients with ischemic and nonischemic cardiomyopathy. TNF-alpha levels were analyzed by an enzyme-linked immunoassay using plasma samples at baseline, 1, and 2 years of follow-up in New York Heart Association class III patients (n = 40 in each of the placebo and amiodarone groups, mean ejection fraction 0.25+/-0.09) who were randomized in the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy, a multicenter, double-blind, placebo-controlled study in which the effect of amiodarone on survival was investigated. TNF-alpha levels were elevated in both groups of patients at baseline, 6.6+/-3.1 and 7.7+/-5.3 pg/ml in the amiodarone and placebo groups, respectively (p = 0.3). There were no significant differences in demographic or clinical variables between the 2 groups. Amiodarone treatment was associated with a significant increase in TNF-alpha levels in patients with ischemic cardiomyopathy, 12.7+/-12.5 and 6.8+/-3.7 pg/ml in the amiodarone and placebo groups, respectively (p = 0.03) at 1 year. No change in TNF-alpha levels was observed in patients with nonischemic cardiomyopathy. In contrast to the in vitro data, amiodarone treatment is associated with an increase in TNF-alpha levels in patients with ischemic cardiomyopathy. This increase is not associated with an adverse effect on survival.

Outcome of moderate carotid artery stenosis in patients who are asymptomatic.

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.

Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma.

Simian virus 40 (SV40) causes mesotheliomas, osteosarcomas, ependymomas, choroid plexus tumors, and lymphomas in hamsters. In humans, SV40 has been detected in tumors of the first four types. Using the polymerase chain reaction (PCR), we tested 29 non-Hodgkin's lymphomas (intermediate and high-grade), 25 posttransplant lymphoproliferative disorders, and 5 AIDS lymphomas for SV40 DNA. PCR analysis revealed that 3 of 29 lymphomas, 6 of 25 posttransplant lymphoproliferative disorders, and 2 of 5 AIDS lymphomas contained SV40 sequences corresponding to the retinoblastoma (RB)-pocket binding domain of SV40 tumor antigen (Tag). However, among positive samples, only one posttransplant lymphoproliferative disorder and one AIDS lymphoma contained the SV40 regulatory region, which suggest a higher viral load in these patients. In parallel experiments, 8 of 12 mesotheliomas tested positive for SV40 for both the RB-pocket binding domain of Tag and the SV40 regulatory region. These data confirm the presence of SV40 in most United States mesotheliomas and indicate that in human non-Hodgkin's lymphomas, the prevalence of SV40 is low.

Second primary tumors in laryngeal cancer: results of long-term follow-up.

PURPOSE: The development of second primary tumors (SPTs) is the most important factor determining the survival in early-stage head and neck cancer patients, whose first tumor has been successfully treated. New methods of examining genetic changes have raised doubts about the validity of the widely held field cancerization hypothesis as the cause of SPTs, and an alternative hypothesis of monoclonal origin has been proposed. The objectives of this study were to look at the pattern of development of SPTs and the possible factors influencing the incidence of SPTs and the survival in early-stage laryngeal cancer with long-term follow-up. METHODS AND MATERIALS: One hundred forty-four consecutive patients of T1N0M0 squamous cell carcinoma of the true vocal cord treated with definitive radiotherapy between 1976 and 1992 were analyzed. The incidence, time to development, and survival of aerodigestive and other SPTs were noted. p53 overexpression indicating a mutated p53 gene was analyzed by immunohistochemistry. RESULTS: With a median follow-up of 6 years (range 2-20 years), 42 patients developed a SPT, 24 in upper aerodigestive tract and lung and 18 at other sites. The actuarial incidence of developing a SPT at 5, 10, and 15 years was 23%, 44%, and 48.7% respectively. The median time interval for development of SPT in an upper aerodigestive tract was 21 months as opposed to 50 months for other sites (p = 0.02). The most common sites of SPTs included lung for upper aerodigestive tract; and prostate, followed by colon, for other sites. The actuarial risk of developing a nonaerodigestive SPT at 5 and 10 years was 35% and 55% respectively. p53 status affected neither the incidence of SPT nor the survival. SPTs were the leading cause of death in these early-stage laryngeal cancer patients. CONCLUSION: The origin of SPTs seems to be multifactorial, involving both the field cancerization effect and an increased baseline genetic predisposition. Until more reliable genetic markers are developed, chemoprevention remains the best treatment option at preventing SPTs in these early-stage patients.

Long-term quality of life after treatment of laryngeal cancer. The Veterans Affairs Laryngeal Cancer Study Group.

OBJECTIVE: To assess long-term quality of life in surviving patients with advanced laryngeal cancer. DESIGN: A follow-up long-term quality-of-life survey of patients randomized to the Veterans Affairs Laryngeal Cancer Study No. 268 on induction chemotherapy and radiation (CT + RT) vs surgery and RT. SETTING AND PATIENTS: Forty-six (71%) of the 65 surviving patients with prior stage III or IV laryngeal cancer who could be contacted completed the survey: 25 from the surgery and RT group and 21 from the CT + RT group. Baseline demographic and clinical characteristics among survey respondents were similar, except that those in the CT + RT group were significantly older (mean, 61.2 years) than those in the surgery and RT group (mean, 55.7 years; P<.05). INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients completed the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, the Medical Outcomes Studies Short-Form 36 (SF-36) general health survey, the Beck Depression Inventory as well as smoking and alcohol consumption surveys. RESULTS: Patients randomized to the CT + RT group had significantly better (P<.05) quality-of-life scores on the SF-36 mental health domain (76.0) than the surgery and RT group (63.0), and also had better HNQOL pain scores (81.3 vs 64.3). Compared with patients who underwent laryngectomy, patients with intact larynges (CT + RT with larynx) had significantly less bodily pain (88.5 vs 56.5), better scores on the SF-36 mental health (79.8 vs 64.7), and better HNQOL emotion (89.7 vs 79.4) scores. More patients in the surgery and RT group (28%) were depressed than in the CT + RT group (15%). CONCLUSION: Better quality-of-life scores in the CT + RT groups appear to be related to more freedom from pain, better emotional well-being, and lower levels of depression than to preservation of speech function.

PBLs of early breast carcinoma patients with a high nuclear grade tumor unlike PBLs of cervical carcinoma patients do not show a decreased TCR zeta expression but are functionally impaired.

Peripheral blood lymphocytes (PBLs) of patients with cervical intraepithelial neoplasia (CIN), cervical carcinoma, or early breast carcinoma were tested for the expression of T cell receptor zeta chain (TCR zeta) and CD16 zeta chain and production of interferon-gamma (IFN gamma) and interleukin (IL) 10. We found that in all patients with CIN and invasive cervical carcinoma, PBLs showed a reduced TCR zeta and CD16 zeta expression and a significant down-regulation in IFN gamma production (a T helper 1 cytokine) after anti-CD3 stimulation. However, the IL 10 secretion (a T helper 2 cytokine) was not diminished after anti-CD3 stimulation. This indicates that only T helper 1 cells are affected by the down-regulation of the TCR zeta chain expression. We also analyzed PBLs of 12 patients with early breast carcinoma. In these patients, we found TCR zeta and CD16 zeta expression down-regulation in 2 of 12 patients. Six of 12 patients had an enhanced TCR zeta expression. The enhanced TCR zeta expression correlated with a reduced IFN gamma expression after anti-CD3 stimulation. These data show that in general PBLs of early breast carcinoma patients, unlike those of cervical carcinoma patients, do not show a decreased TCR zeta expression. However, a functional impairment of T cells was observed in the subgroup of early breast carcinoma patients with a high nuclear grade of their tumor.