Body size throughout the life-course and incident benign prostatic hyperplasia-related outcomes and nocturia.

BACKGROUND: Existing evidence suggests that there is an association between body size and prevalent Benign Prostatic Hyperplasia (BPH)-related outcomes and nocturia. However, there is limited evidence on the association between body size throughout the life-course and incident BPH-related outcomes. METHODS: Our study population consisted of men without histories of prostate cancer, BPH-related outcomes, or nocturia in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 4710). Associations for body size in early- (age 20), mid- (age 50) and late-life (age ≥ 55, mean age 60.7 years) and weight change with incident BPH-related outcomes (including self-reported nocturia and physician diagnosis of BPH, digital rectal examination-estimated prostate volume ≥ 30 cc, and prostate-specific antigen [PSA] concentration > 1.4 ng/mL) were examined using Poisson regression with robust variance estimation. RESULTS: Men who were obese in late-life were 25% more likely to report nocturia (Relative Risk (RR): 1.25, 95% Confidence Interval (CI): 1.11-1.40; p-trendfor continuous BMI < 0.0001) and men who were either overweight or obese in late-life were more likely to report a prostate volume ≥ 30 cc (RRoverweight: 1.13, 95% CI 1.07-1.21; RRobese: 1.10, 95% CI 1.02-1.19; p-trendfor continuous BMI = 0.017) as compared to normal weight men. Obesity at ages 20 and 50 was similarly associated with both nocturia and prostate volume ≥ 30 cc. Considering trajectories of body size, men who were normal weight at age 20 and became overweight or obese by later-life had increased risks of nocturia (RRnormal to overweight: 1.09, 95% CI 0.98-1.22; RRnormal to obese: 1.28, 95% CI 1.10-1.47) and a prostate volume ≥ 30 cc (RRnormal to overweight: 1.12, 95% CI 1.05-1.20). Too few men were obese early in life to examine the independent effect of early-life body size. Later-life body size modified the association between physical activity and nocturia. CONCLUSIONS: We found that later-life body size, independent of early-life body size, was associated with adverse BPH outcomes, suggesting that interventions to reduce body size even late in life can potentially reduce the burden of BPH-related outcomes and nocturia.

Psoriasis: The Skin I'm In. Development of a behaviour change tool to improve the care and lives of people with psoriasis.

BACKGROUND: Psoriasis is a long-term skin condition associated with considerable life impairment. Extensive literature regarding the needs of patients with psoriasis is not translated into clinical practice. AIM: To explore and communicate the experience of living with psoriasis and interacting with healthcare professionals (HCPs). METHODS: In total, 21 patients attending a tertiary adult psoriasis service were interviewed individually. Interviews were recorded and transcribed, then the transcripts were examined and thematic analyses and qualitative content analysis performed. The results were communicated via a short film. RESULTS: Three key themes were identified: comparison with cancer, misalignment of response with need and fear of social exclusion. Cancer comparison subthemes included poorer services, lack of awareness and trivialization of psoriasis compared with cancer. Misalignment subthemes related to lack of knowledge and inappropriate response of HCPs and society towards psoriasis. Fear of social exclusion subthemes included erroneous belief of psoriasis being contagious and the expectation of rejection. Consequent emotions of fear, shame and anxiety resulted in avoidant behaviours, which perpetuated social exclusion. Participants valued active listening, shared decision-making and communication of hope regarding treatment by HCPs. CONCLUSION: Despite extensive research into psoriasis and the availability of effective treatment for many patients, people with psoriasis live unnecessarily impaired lives and have unsatisfactory healthcare experiences. Storytelling techniques provide a method to communicate scientific information in a way that may drive change in delivery of healthcare and improve the lives of patients.

Predicting coronary heart disease in remote settings: a prospective, cross-sectional observational study.

BACKGROUND: Coronary heart disease (CHD) places a major burden on the Australian health care system. Determining the likelihood of CHD in a patient presenting with chest pain can be particularly difficult in a remote setting where access to transportation and specialised investigations including myocardial stress studies and coronary angiography can be difficult and delayed. The objective is to develop a predictive model for determining the risk of CHD, including the value of high sensitivity C-reactive protein (hsCRP), in patients presenting with chest pain with a particular emphasis on resources and information likely to be available in a remote primary health care setting. METHODS: A prospective, cross-sectional observational study of patients with no prior diagnosis of CHD presenting to a specialist chest pain assessment clinic at Cairns Hospital from November 2012 to May 2013. RESULTS: Out of the 163 participants included in the study analyses, a total of 38 were classified as CHD likely (23.3% (95% CI 17.1-30.6)). Logistic regression modelling identified two factors that were independently associated with likely CHD, namely the presence of typical chest pain (OR 83.7 (95% CI 21.7-322.1)) and an abnormal baseline ECG (OR 12.8 (95% CI 1.9-86.0)). CONCLUSION: In this study, it was demonstrated that the presence of typical chest pain and an abnormal resting ECG, remain the cornerstone of predicting a subsequent diagnosis of CHD. This information is easily accessible in remote primary health care and should be utilised to expedite assessment in patients presenting with symptoms suggestive of CHD.

Prostate involvement during sexually transmitted infections as measured by prostate-specific antigen concentration.

BACKGROUND: We investigated prostate involvement during sexually transmitted infections by measuring serum prostate-specific antigen (PSA) as a marker of prostate infection, inflammation, and/or cell damage in young, male US military members. METHODS: We measured PSA before and during infection for 299 chlamydia, 112 gonorrhoea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases, and 256 controls. RESULTS: Chlamydia and gonorrhoea, but not NCNGU, cases were more likely to have a large rise (40%) in PSA than controls (33.6%, 19.1%, and 8.2% vs 8.8%, P<0.0001, 0.021, and 0.92, respectively). CONCLUSION: Chlamydia and gonorrhoea may infect the prostate of some infected men.

Isokinetic thigh muscle ratios in youth football: effect of age and dominance.

This study aimed to analyse the effect of age on muscle peak torque (PT), and Hamstring (H): Quadricep (Q) ratio in elite youth footballers. To date, no study has considered age-group playing level and pubertal development in this population. One hundred and fifty-seven elite youth footballers in the age groups U12 to U18 volunteered to participate in this study, 133 of these were further grouped for pubertal development. Prior to testing subjects completed separate familiarisation, a three minute cycle ergometer warm up (resistance 50-60W), and two sub-maximal repetitions. Concentric and eccentric isokinetic PT measures for reps 2-4 of H and Q muscle action were taken at 60 degrees s (-1). From this, conventional and functional H: Q ratio was calculated along with dominant: non dominant ratio for the concentric Q and H, and eccentric H conditions. Significant main effects were observed for the age/pubertal development group and PT in all muscles and conditions (P<0.05). Of particular interest was a significant main effect for age and Functional H: Q (P<0.05), which suggested a move away from equality at U18. Our study provides normative data for coaches, trainers and clinicians working with youth footballers and may also have connotations for injury prevention and performance.

Integrating science and human values for cancer patient care.

The burden of cancer continues to increase globally, with substantial personal, societal, and economic consequences. Population growth and aging underlie this increase-a reflection of the effect of population health interventions in the last two centuries. Much of this gain has come through observation, derivation of evidence, and rigorous application of valid science to the public, both healthy and affected by diseases such as cancer. Increasingly, molecular medicine will affect the knowledge of cause and the personalization of therapy. However, science informs the decision-making process and places evidence within the beliefs of individuals and society as they relate to innovation, judgment, and values-the "logic" underlying alignment of conventional and complementary (holistic) care as a basis for compelling, consistent, and confident decisions.

Contemporary mortality due to acute myocardial infarction, unstable angina and exertional angina in a population in South East London.

BACKGROUND: Data on the contemporary mortality of coronary heart disease (CHD) are surprisingly sparse. AIM: To describe the contemporary mortality of all manifestations of CHD. DESIGN: Prospective follow-up of patients with a first presentation of CHD in a defined population. METHODS: We studied 537 patients with a first presentation of acute myocardial infarction, unstable angina or new exertional angina in Bromley Health Authority, London (population 295,000). Patients were prospectively monitored for cardiac and non-cardiac mortality for a median of 6 years. RESULTS: During a median 6 years follow-up, there were 88 (16%) deaths. Survival free from cardiac death was not significantly different between unstable angina (92%) and new exertional angina (94%), but was lower for acute myocardial infarction (84%). DISCUSSION: Mortality from CHD appears to be falling. However, efforts to prevent myocardial infarction should continue to be a priority, because on-going early mortality remains high. New exertional angina should be diagnosed and managed promptly, as its mortality is similar to that of unstable angina.

Maternal and fetal outcome after invasive cervical cancer in pregnancy.

Invasive carcinoma of the cervix is the most common gynecologic malignancy to occur during the reproductive years. To analyze the effects of pregnancy on the course and survival of invasive cervical cancer, we compared 40 women with invasive cervical cancer to 89 nonpregnant controls matched for age, calendric year of diagnosis, stage, and tumor type. Additionally, we compared the distribution of invasive cervical cancer stages among the 40 pregnant women with that among the 1,963 cases of invasive cervical cancer treated during the same 30 years in women less than 45 years of age registered in the same hospital. To evaluate pregnancy outcome, we compared babies born to women with invasive cervical cancer to babies born of women matched for maternal age and not exposed to known teratogens or reproductive risks during pregnancy. Thirty-year survival of pregnant women with invasive cervical cancer was identical to that of their matched controls. Women having invasive cervical cancer were 3.1 times more likely to be diagnosed with stage I disease (95% confidence interval, 1.6 to 6.2). Additionally, they had a significantly lower chance of being diagnosed with stages III and IV (P = .02). Babies born to women with invasive cervical cancer were similar in gestational age and rates of prematurity but had a lower birth weight than the matched controls. There were two stillbirths among the 24 pregnancies that continued to term (8%), not statistically different from the 1.1% rate for Ontario. Our data suggest that pregnancy per se does not adversely affect the survival of women with invasive cervical cancer. However, this study provides evidence that pregnant women are more likely to present with early disease because of regular, pregnancy-related obstetric exams. Moreover, there is an increased risk for stillbirth, which should lead to follow-up of these patients by a high-risk perinatal unit.

Patterns of disease in localized extranodal lymphomas.

The site of origin of lymphoid tissue is an important determinant of lymphocyte migration patterns. The association of gastrointestinal (GI) and Waldeyer's ring lymphoma and the unique lymphocyte migration pattern of gut-associated lymphoid tissue (GALT) have been previously described. To establish whether predictive clinical patterns of disease occur in localized Non-Hodgkin's lymphoma, survival and relapse patterns for 496 patients with stage I and II non-Hodgkin's lymphoma (NHL) treated with loco-regional irradiation (XRT) alone were examined. We identified 139 patients with GALT lymphoma (defined as arising from primitive gut and including Waldeyers' ring, thyroid, and GI lymphomas) and 87 patients with extranodal non-gut-associated lymphoma (ENL). Survival and relapse data were assessed in multifactorial analysis to correct for previously identified other prognostic variables. GALT lymphomas (GALT-L) have a survival advantage compared with other ENL (P = .017) independent of stage and histology. A difference in distant relapse (DR) rate between GALT-L and other ENL (P = .0002) was also identified. The presentation site of localized extranodal NHL is predictive of clinical behavior and is an independent determinant of outcome. This may be an expression of lymphocytic origin and determinants of migration patterns.

Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation.

PURPOSE: To evaluate the efficacy of carmustine (BCNU), etoposide, cytarabine (Ara-C), and melphalan (mini-BEAM) as salvage therapy in patients with relapsed or refractory Hodgkin's disease who were potentially eligible to undergo intensive therapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Forty-four patients with refractory or relapsed Hodgkin's disease after front-line combination chemotherapy referred for consideration of ABMT were treated with mini-BEAM (BCNU 60 mg/m2 on day 1, etoposide 75 mg/m2 on days 2 to 5, Ara-C 100 mg/m2 twice per day on days 2 to 5, and melphalan 30 mg/m2 on day 6) to maximum response. Eleven patients were refractory to primary chemotherapy. Twenty-three patients were treated in first relapse and 10 in second or subsequent relapse; 21 received mini-BEAM as their first salvage regimen. Patients were restaged to determine disease status immediately before intensive therapy and transplant. RESULTS: The overall response rate was 84% (exact 95% confidence interval [CI], 70% to 92%), with a complete response (CR) rate of 32% (95% CI, 20% to 47%) and a partial response (PR) rate of 52%. No treatment-related deaths were observed. Myelosuppression was the major toxicity. Almost all patients required platelet transfusions. Eighty-four percent were given RBC transfusions, and 54% required intravenous antibiotics for fever while neutropenic. CONCLUSION: Mini-BEAM is a safe and effective regimen for treatment of refractory or relapsed Hodgkin's disease. Further studies are required to determine if responding patients have improved disease-free survival (DFS) after intensive therapy and ABMT.

Secondary malignancies after bone marrow transplantation in adults.

PURPOSE: The records of 557 consecutive adult recipients of allogeneic-related and -unrelated and syngeneic bone marrow transplants (BMTs) were reviewed to determine the incidence of secondary cancers. PATIENTS AND METHODS: Four hundred fifty-six patients were transplanted for acute lymphocytic leukemia (ALL; n = 79), acute myelogenous leukemia (AML; n = 182), and chronic myelogenous leukemia (CML; n = 195); 42 patients were transplanted for aplastic anemia (AA) and 59 for a variety of other hematologic and nonhematologic disorders, malignant and nonmalignant. Conditioning regimens included high-dose chemotherapy with or without total-body irradiation (TBI). Statistical analyses determined the cumulative incidence of developing a secondary cancer and elucidated the associated risk factors. Complete records (1 to 24 years of follow-up) on all patients were available. RESULTS: Nine patients developed 10 secondary cancers for a cumulative actuarial risk of 12% (95% confidence interval [CI], 4.3 to 23.0) 11 years after transplant. The age-adjusted incidence of secondary cancer was 4.2 times higher than that of primary cancer in the general population. Eight of the 10 were epithelial in origin and three were cutaneous. TBI and acute graft-versus-host disease (GVHD) with a severity > or = grade II were associated with the development of any secondary cancer. On the other hand, chronic GVHD was a risk factor only for the development of secondary skin neoplasms. CONCLUSION: Adult recipients of BMT face a significant risk of developing a secondary malignancy. Their risk is similar to that of other patients with hematologic malignancies who are treated with chemoradiotherapy only. Epithelial tumors, rather than the more commonly reported Epstein-Barr virus (EBV)-associated lymphomas, were most common. The fact that we did not routinely use T-cell-depleted marrow grafts nor anti-T-cell immunoglobulin for the treatment of acute GVHD may explain this variance.

Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting.

The Ann Arbor classification for describing the stage of Hodgkin's disease at initial presentation has formed the basis upon which treatment is selected and has allowed comparison of results achieved by different investigators for almost two decades. A meeting was convened to review the classification and modify it in the light of experience gained in its use and new techniques for evaluating disease. It was concluded that the structure of the classification be maintained. It was particularly recommended: (1) that computed tomography (CT) be included as a technique for evaluating intrathoracic and infradiaphragmatic lymph nodes; (2) that the criteria for clinical involvement of the spleen and liver be modified to include evidence of focal defects with two imaging techniques and that abnormalities of liver function be ignored; (3) that the suffix 'X' to designate bulky disease (greater than 10 cm maximum dimension) be introduced; and (4) that a new category of response to therapy, unconfirmed/uncertain complete remission (CR[u]), be introduced to accommodate the difficulty of persistent radiological abnormalities of uncertain significance.

Prognostic groups for management of localized Hodgkin's disease.

Two hundred fifty-two patients receiving radical irradiation for clinical stages I and II Hodgkin's disease between 1968 to 1977 had an actuarial ten-year survival rate of 78% and a relapse-free rate of 61%. Sixty-seven patients receiving chemotherapy followed by radiation had a 78% survival rate and a 63% relapse-free rate. Independent prognostic factors for survival and relapse were age, stage, and histology. Disease bulk was predictive only of relapse. Neither site of presentation above or below the diaphragm nor presence of mediastinal involvement was predictive for survival or relapse; however, patients with large mediastinal masses (greater than or equal to 10 cm absolute diameter) had a significantly higher intrathoracic failure rate with conventional mantle irradiation. Analysis of failure, according to age, clinical stage, and histologic type, showed three groups of patients defined according to the risk of relapse with radiation therapy: those with isolated upper cervical stage IA disease (group 1, relapse rate 8%), younger patients with localized stages I and II disease of favorable histologic type (group 2, relapse rate 35%), and older patients with extensive or symptomatic stages I and II disease of less favorable histologic type (group 3, relapse rate 70%). Subsequent analysis of radiation treatment volume indicates that the use of upper abdominal irradiation for patients in group No. 2 could yield results equivalent to those achieved with radiation therapy for surgically staged patients.

Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group.

PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.

Fetal outcome after in utero exposure to cancer chemotherapy.

BACKGROUND: Cancer is the second leading cause of death of women during the reproductive years, and its occurrence in pregnancy is between 0.07% and 0.1%. METHODS: To analyze the effect of cancer on pregnancy, we compared 21 pregnancies occurring during 30 years in women who received chemotherapy for their cancer with a control group matched for maternal age and composed of women not exposed to known teratogens or reproductive risks during pregnancy. RESULTS: Of 13 women exposed to chemotherapy during the first trimester, two of five whose pregnancies continued to term had major malformations in their infants, four had spontaneous abortions, and four had therapeutic abortions. Of four women with second-trimester exposure to chemotherapy, two had normal live births, one had a stillbirth, and one had a therapeutic abortion. All four pregnancies exposed to chemotherapy during the third trimester resulted in healthy live births. Infants exposed to chemotherapy had statistically significantly lower birth weights than their matched controls (2227 +/- 558 g vs 3519 +/- 272 g, P less than .001), due to both significantly lower gestational age and substantial intrauterine growth retardation (P less than .01). The trend for higher rate of stillbirth (1/11) agrees well with 10 stillbirths among all women with cancer in pregnancy without and with chemotherapy who gave birth (n = 223), when compared with the population of Ontario (P less than .0005). CONCLUSIONS: This study confirms the increased likelihood of spontaneous abortions and major birth defects when chemotherapy is used during embryogenesis, whereas such a risk is not apparent beyond the first trimester. Because of the higher risk of stillbirth and intrauterine growth retardation, women with cancer should be monitored closely by a high-risk obstetric unit to define the optimal time of delivery.

GM-CSF therapy for delayed engraftment after autologous bone marrow transplantation.

Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after high-dose therapy and autologous bone marrow transplantation (ABMT). Three patients responded to a 14-day course of GM-CSF (10 micrograms/kg body weight/day) with at least a sevenfold rise in circulating granulocytes and a corresponding increase in granulopoietic activity in the bone marrow. A fourth patient died of infection on the 8th day of GM-CSF therapy with no evidence of response, and the remaining two, one of whom received a lower dose of GM-CSF (5 micrograms/kg/day), did not respond. There was no change in platelet or red cell transfusion requirements in any patient during the treatment. In two of the three responders, the granulocyte counts returned to pretreatment levels by 4 and 7 weeks after stopping the drug, respectively. We observed a marked increase in marrow-derived as well as in circulating granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) by the end of the 14-day course of GM-CSF in the three responders. There was no change in the frequency of circulating or marrow-derived erythroid (erythroid burst-forming units, BFU-E) or multilineage (multilineage colony-forming units, CFU-GEMM) progenitors. The results indicate that GM-CSF therapy in patients with markedly delayed engraftment after ABMT may stimulate granulopoiesis, but the effect is transient in some patients.

Intraprostatic inflammation is positively associated with serum PSA in men with PSA <4 ng ml(-1), normal DRE and negative for prostate cancer.

BACKGROUND: Biopsies performed for elevated serum PSA often show inflammatory infiltrates. However, the influence of intraprostatic inflammation on serum PSA in men without biopsy indication and negative for prostate cancer has not been described in detail. METHODS: We studied 224 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) who underwent end-of-study biopsy per trial protocol, had PSA <4 ng ml(-1), normal digital rectal examination and a biopsy negative for cancer. We analyzed data from hematoxylin and eosin-stained slides containing a mean of three biopsy cores. Inflammation measures included the extent (percentage of tissue area with inflammation) and intensity (product of scores for extent and grade) of total, acute and chronic inflammation in the entire tissue area examined, and by tissue compartment. We calculated median measures of inflammation by prebiopsy serum PSA tertile (>0 to ≤0.8, >0.8 to ≤1.5 and >1.5 to <4.0 ng ml(-1)). We estimated the association between percentage of tissue area with inflammation and natural logarithm of PSA using linear regression adjusting for age at biopsy. RESULTS: Median percentage of tissue area with inflammation increased from 2 to 5 to 9.5% across PSA tertiles (P-trend <0.0001). For every 5% increase in tissue area with inflammation, log PSA increased by 0.061 ng ml(-1) (P=0.0002). Median extent and intensity scores increased across PSA tertiles in luminal and intraepithelial compartments for acute inflammation and in stromal and intraepithelial compartments for chronic inflammation (all P-trend ≤0.05). CONCLUSIONS: In men without clinical suspicion of prostate cancer, greater overall inflammation, luminal and intraepithelial acute inflammation and stromal and intraepithelial chronic inflammation were associated with higher serum PSA.

Radiation therapy in clinical stage I and II Hodgkin's disease. The Princess Margaret Hospital Lymphoma Group.

A review of the Princess Margaret Hospital experience over the last 20 years in treating clinically staged patients with stage I and II Hodgkin's disease was performed to analyse the impact of patient selection and extended field radiation on relapse and survival. Of the 878 patients with stage I and II Hodgkin's disease, 521 with clinical stages I and II received radiation alone as the initial treatment. The actuarial survival for all stage I and II patients was 85.1% at 5 years and 76.2% at 10 years, and for clinically staged patients treated with radiation alone, 87.2 and 77.6%, respectively. The relapse-free rate (RFR) for all clinical stage I and II patients treated with radiotherapy (RT) alone was 70.1% at 5 years and 65.8% at 10 years. Significant prognostic factors for RFR and survival included age, stage and histology. In addition, the extent of radiation was identified as an independent prognostic factor for survival as well as for relapse. The RFR for those treated with involved field RT was 58.4% at 5 years and 50.5% at 10 years; for patients treated with mantle RT, 69.9 and 65.6%, and those treated with extended field RT 77.4 and 75.8%, respectively. In a highly selected group of patients with no adverse features, i.e. with stages IA-IIA, lymphocyte predominant or nodular sclerosis histology, erythrocyte sedimentation rate < 40, age < 50, no large mediastinal mass, and no E-lesions--the policy of mantle RT (M) and extended field RT (EF) produced comparable 5-year relapse-free rates (M, 84.9%; EF, 87.1%; P = 0.53). We conclude that a policy of treatment selection based upon clinicopathological prognostic factors and the use of extended field RT confers excellent results in the treatment of clinical stage I and II Hodgkin's disease.

Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group.

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.

Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients.

This report from the Canadian survey of thyroid cancer describes 1,074 patients with papillary thyroid cancer and 504 with follicular thyroid cancer followed for four to 24 years. The study groups included more patients with "advanced" disease and fewer with "early" disease than in the general population because these patients were referred to radiotherapy cancer centers, sometimes routinely, but often because referring physicians believed that certain clinical features indicated the need for additional treatment. Although this report is subject to all the problems of retrospective studies, a careful assessment of the pretreatment extent of disease combined with a long follow-up period has allowed an analysis of prognostic factors with considerable confidence. Univariate analysis of 12 possible prognostic factors (excluding treatment) demonstrated that nine of them were of statistical significance: postoperative status, age at diagnosis, extrathyroidal invasion, distant metastases, nodal involvement, differentiation, sex, tumor size, and pathologic type (in descending order of importance). Multivariate analysis was carried out using cause-specific survival rates. Independently important prognostic factors at initial treatment were age at diagnosis, extrathyroidal invasion, and degree of differentiation histologically for papillary cancers; and extrathyroidal invasion, distant metastases, primary tumor size, nodal involvement, age at diagnosis, and postoperative status for follicular cancers. The prognostic factors for tumor recurrence were quite different for the papillary and follicular cancers and ranked differently for the two groups.