Laparotomy versus no laparotomy in the management of early-stage, favorable-prognosis Hodgkin's disease: a decision analysis.

PURPOSE: To perform a decision analysis that compared the life expectancy and quality-adjusted life expectancy of early-stage, favorable-prognosis Hodgkin's disease (HD) managed with and without staging laparotomy, incorporating data on treatment outcomes of HD in the modern era. METHODS: We constructed a decision-analytic model to compare laparotomy versus no laparotomy staging for a hypothetical cohort of 25-year-old patients with clinical stages I and II, favorable-prognosis HD. Markov models were used to simulate the lifetime clinical course of patients, whose prognosis depended on the true pathologic stage and initial treatment. The baseline probability estimates used in the model were derived from results of published studies. Quality-of-life adjustments for procedures and treatments, as well as the various long-term health states, were incorporated. RESULTS: The life expectancy was 36.67 years for the laparotomy strategy and 35.92 years for no laparotomy, yielding a net expected benefit of 0.75 years for laparotomy staging. The corresponding quality-adjusted life expectancies for the two strategies were 35.97 and 35.38 quality-adjusted life years (QALYs), respectively, resulting in a net expected benefit of laparotomy staging of 0.59 QALYs. Sensitivity analysis showed that the decision of laparotomy versus no laparotomy was most heavily influenced by the quality-of-life weight assigned to the postlaparotomy state. CONCLUSION: Our model predicted that on average, for a 25-year-old patient, proceeding with staging laparotomy resulted in a gain in life expectancy of 9 months, or 7 quality-adjusted months. These results suggest that a role remains for surgical staging in the management of early-stage HD.     

Early stage infradiaphragmatic Hodgkin's disease: results of radiotherapy and review of the literature.

PURPOSE: To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkin's disease (IDHD). METHODS AND MATERIALS: During the period 1965-1997, 847 patients with early stage Hodgkin's disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT. RESULTS: The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields. CONCLUSIONS: In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.     

Treatment of early and intermediate stages of supradiaphragmatic Hodgkin's disease: The Swedish National Care Programme Experience

PURPOSE: Since 1985 a Swedish National Care Programme has provided tailoredprinciples for the staging, treatment and follow-up of patientswith Hodgkin's disease (HD). This report presents treatmentresults for all patients below 60 years of age who were diagnosedwith early and intermediate stages, between 1985 and 1989. PATIENTS AND METHODS: During that period, 210 patients with supradiaphragmatic HDin clinical (CS) and pathological (PS) stages IA + IIA, PS IB+ IIB, and PS III₁, A were diagnosed in five Health Care Regionsin Sweden. In patients with CS IA, staging laparotomy was notrecommended provided that the radiological assessment of theabdomen was adequate, whereas this procedure was recommendedin stages CS IB, IIA and IIB in order to minimize treatment.In the absence of bulky mediastinal disease, patients with CS+ PS IA and PS IIA were treated with mantle (occasionally mini-mantle)irradiation alone, while patients with bulky disease, as wellas those with stages PS IB + IIB + III₁A, were treated withone cycle of MOPP/ABVD prior to mantle (PS III₁, A sub-totalnodal) irradiation. Full chemotherapy followed by radiotherapy to initial siteswith bulky disease was recommended for patients with CS IIAwho did not undergo laparotomy. RESULTS: After a median follow-up in excess of five years, treatmentresults are ‘favourable’ for all stages, providedthe recommendations were followed. In patients with CS + PSIA treated according to the recommendations, recurrence rateswere 14% (9/65) with all but one patient (64/65, 98%) remainingin continuous first or second remission. These figures wereworse in patients treated inadequately (9/26 [35%] and 22/26[85%], respectively). In PS IIA, adequately-treated patientshad a recurrence rate of 13% (7/52) whereas 5/7 (71%) of thosewith bulky disease who received only mantle irradiation developedrecurrences. Similar patterns also emerged in patients withCS IIA, PS IB + IIB and PS III, A. CONCLUSIONS: The tailored principles, which usually entail less staging and/ortreatment than is generally the case, produced favourable resultswhen applied to an entirely un-selected group of patients withearly and intermediate stages of HD. Hodgkin's disease, combined-modality treatment, radiotherapy     

Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease.

PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.     

Mantle irradiation alone for clinical stage I-II Hodgkin's disease: long-term follow-up and analysis of prognostic factors in 261 patients.

PURPOSE: To evaluate mantle radiotherapy (MRT) alone as the initial therapy of patients with clinical stage (CS) I-II Hodgkin's disease (HD). PATIENTS AND METHODS: We performed a retrospective study of patients treated with MRT alone for CS I-II supradiaphragmatic HD between 1969 and 1994. Prognostic factor analysis was performed for progression-free survival (PFS) and overall survival (OS). Outcome was also assessed in favorable cohorts defined in the literature. RESULTS: There were 261 eligible patients. The median follow-up period for surviving patients was 8.4 years (range, 1.8 to 27.4 years). The 10-year OS rate was 73%. Multifactor analysis for OS showed that age was the only important prognostic factor. The 10-year PFS rate was 58%. On multifactor analysis for PFS, the most important prognostic factors were clinical stage, B symptoms, histology, number of sites, and tumor bulk. The 10-year PFS rate for lymphocyte-predominant disease was 81% for stage I and 78% for stage II. In favorable patient cohorts defined in the literature, the 10-year PFS rate ranged from 70% to 73% for the whole group and from 71% to 90% in patients with favorable stage I disease, but only from 48% to 57% in patients with favorable stage II disease. On competing-risks analysis, the cumulative 10-year incidence of first site of failure in the para-aortic/splenic region alone was 10.5%. Sixty percent of relapsed patients remain progression-free at 10 years after chemotherapy salvage. CONCLUSION: These results support the use of MRT alone in patients with favorable CS I HD and CS I-II HD with lymphocyte-predominant histology. The remainder of patients with CS I-II HD require more intensive treatment.     

Early-stage hodgkin’s disease

Treatment of Hodgkin’s disease (HD) is strictly dependent on stage. Historically, early-stage HD included the limited stages I, II, and IIIA (according to the Cotswolds modification of the Ann Arbor classsification), whereas advanced HD included stage III with B symptoms and stage IV. It was then observed that early-stage HD with certain clinical risk factors had a significantly worse outcome. As a consequence, several studies defined these patients as suffering from early-stage unfavorable (or intermediate-stage) HD, demanding a more aggressive treatment. The treatment of early-stage HD is changing strikingly. Until recently, extended-field (EF) irradiation has been considered the standard treatment. However, because of the recognition of its high relapse rate and fatal long-term effects, EF radiotherapy is now being abandoned by most study groups. Instead, for favorable early-stage HD, mild chemotherapy for control of occult disease is combined with involved-field (IF) irradiation. In early-stage unfavorable (intermediate) HD, four cycles of chemotherapy plus IF irradiation is accepted as standard treatment.     

Radiation Dose Reduction in Early-Stage Hodgkin Lymphoma

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

Survival of patients with localized histiocytic lymphoma.

Twenty of 65 patients with diffuse histiocytic lymphoma were identified by staging laparotomy as being in pathologic stages (PS) I, I(E), II, II(E). Six of the 20 patients were treated with total nodal, 10 with extended mantle, and four with involved-field radiotherapy. The survival rate and relapse-free survival at five years were 71% and 78%, respectively. All relapses occurred within the first year and were confined to patients with PS II disease and four or more sites of involvement. Accurate pathologic staging identifies patients who are potentially curable with radiotherapy. Further studies are required to determine the treatment necessary to achieve cure in PS II patients with more than four sites of involvement.     

Combined Modality Treatment for Poor Prognosis Stages I and II Hodgkin's Disease

Recommendations for the treatment of "poor prognosis" stages I and II Hodgkin's disease (HD) depend on the extent of staging. For centers that favor exploratory laparotomy and splenectomy, the standard treatment after negative surgical staging remains subtotal lymphoid irradiation. However, most centers recommend excluding selected patients from surgical staging. In particular, most specialists agree that patients with bulky mediastinal disease (large mediastinal adenopathy) should receive combined chemotherapy and radiotherapy without surgical staging. Centers that have eliminated staging laparotomy rely on clinical staging and have identified a number of poor prognostic factors that influence treatment recommendations. In 1995, the following factors were considered to be associated with an unfavorable prognosis in clinical stages (CS) I and II HD: advanced age, systemic symptoms, high erythrocyte sedimentation rate, large number of individual sites, and presence of bulky disease. For example, these factors have been used in the H7 and H8 European Organization for the Research and Treatment of Cancer trials and have been adopted by almost 100 participant groups. For CS I and II patients with unfavorable presentations, the literature suggests that the optimal treatment is a combination of chemotherapy and radiotherapy. Nevertheless, the optimal delivery of chemotherapy and radiotherapy is still debated and a number of the questions listed below are awaiting answers: 1. The chemotherapy schedule: Mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alone can no longer be recommended (for toxicity reasons) for the routine treatment of poor prognosis CS I and II HD. Many centers, on theoretical arguments, favor seven or eight drug combinations (MOPP/ABV hybrid), although the advantage of these combinations in toxicity and efficacy over doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone has not been demonstrated. 2. The number of chemotherapy courses: Most groups use six cycle regimens, but reduction to three to four cycles is currently being investigated both in pilot and randomized studies. 3. Timing of chemotherapy: Chemotherapy is given first in most instances. Whether or not a "sandwiched" scheme is better than all the chemotherapy given upfront remains to be answered. 4. Volumes to be irradiated: Data suggest that the irradiated volumes can be safely limited to initially involved lymph node regions after effective chemotherapy. The question is presently being addressed in a few ongoing randomized trials. 5. Radiation dose to be delivered: The decrease of the radiation dose to 35 to 36 Gy after effective chemotherapy has gained a wide acceptance. Further dose reduction is being investigated. In conclusion, except for selected CS I and II patients still referred for surgical staging, combined modality therapy appears to be the treatment of choice for poor prognosis CS I and II HD.     

Stage IA-IIB Hodgkin's disease: staging and treatment of patients with large mediastinal adenopathy

Ninety-two patients with clinically staged (CS) IA-IIB Hodgkin's disease (HD) with large mediastinal adenopathy (LMA) underwent three different staging and treatment approaches between April 1969 and December 1984. These approaches included: (1) staging laparotomy followed by radiation therapy (RT) alone; (2) staging laparotomy followed by combined RT and chemotherapy (CMT); or (3) clinical staging followed by CMT. Patients treated with CMT were more likely to have "B" symptoms, extension into extranodal sites, or stage III disease. Patients treated with RT alone had a significantly higher risk of relapse as compared to patients receiving CMT. No overall survival differences were seen between the three groups of patients. For patients treated with CMT without RT to the spleen or abdominal nodes, the risk of relapse in the abdomen was low (4%). These data suggest that for those CS I-II HD patients with LMA who are treated with CMT, the role for staging laparotomy and abdominal irradiation is limited. RT alone remains an option for some patients with LMA, but careful assessment of the anatomic extent of thoracic disease as well as staging laparotomy is essential if such treatment is recommended.     

Conditional survival estimates improve over time for patients with advanced melanoma

BACKGROUND:

Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma‐specific CS estimates to help clinicians promote more informed patient decision making.

METHODS:

Patients with melanoma and at least 5 years of follow‐up were identified from the Surveillance Epidemiology and End Results registry (1988‐2000). By using the methods of Kaplan and Meier, stage‐specific, 5‐year CS estimates were independently calculated for survivors for each year after diagnosis. Stage‐specific multivariate Cox regression models including baseline survivor functions were used to calculate adjusted melanoma‐specific CS for different subgroups of patients further stratified by age, gender, race, marital status, anatomic tumor location, and tumor histology.

RESULTS:

Five‐year CS estimates for patients with stage I disease remained constant at 97% annually, while for patients with stages II, III, and IV disease, 5‐year CS estimates from time 0 (diagnosis) to 5 years improved from 72% to 86%, 51% to 87%, and 19% to 84%, respectively. Multivariate CS analysis revealed that differences in stages II through IV CS based on age, gender, and race decreased over time.

CONCLUSIONS:

Five‐year melanoma‐specific CS estimates improve dramatically over time for survivors with advanced stages of disease. These prognostic data are critical to patients for both treatment and nontreatment related life decisions. Cancer 2010. © 2010 American Cancer Society.     

Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease

Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.     

The management of localized, infradiaphragmatic Hodgkin's disease: experience of a rare clinical presentation at St Bartholomew's Hospital

Between 1969 and 1982, 23 previously untreated patients with Hodgkin's disease (HD) confined to infradiaphragmatic sites were treated at St Bartholomew's Hospital. The distinguishing clinical characteristics of the patient population were a male: female ratio of 20:3. The mean age was 39 years, which was significantly older (P less than 0.05) than the mean age of patients with supradiaphragmatic HD (32 years) referred during the same period. Sixteen patients underwent formal pathological staging while one additional patient underwent a diagnostic laparotomy without splenectomy. The final pre-treatment stages were PS IA: 5; PS IIA: 11; CS IIA: 1; PS IIB: 1; CS IIB 5. Splenic involvement correlated closely with the number of nodal sites involved, being detected in 1/7 patients with one site only compared with 8/9 with more (P less than 0.001). Complete remission (CR) was achieved in 21 (91 per cent) patients: 12/12 following 'inverted Y' radiotherapy (RT) and 9/11 following combination chemotherapy. Twenty patients remain alive and 18 continue without recurrence of HD between 15 months and 12 years. All patients who failed to enter CR or who relapsed had presented with three or more sites of involvement or with constitutional ('B') symptoms. These results confirm the generally good prognosis of this uncommon presentation of HD and also suggest that prognosis is determined by the bulk of disease rather than its precise anatomical localization, provided that appropriate therapy is administered.     

Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma.

PURPOSE: Early-stage nasopharyngeal carcinoma (NPC) continues to carry a failure rate of 15% to 30% when treated with radiotherapy alone; the benefit of concomitant radiotherapy and chemotherapy (CCRT) in early-stage NPC is unclear. The purpose of this report is to describe our efforts to improve treatment outcome in early-stage NPC after CCRT. PATIENTS AND METHODS: Of 189 newly diagnosed NPC patients without evidence of distant metastases who were treated in our institution between 1990 and 1997, 44 presented with early-stage (stage I and II) disease according to the American Joint Committee on Cancer (AJCC) 1997 NPC staging system. Twelve of these patients were treated with radiotherapy alone and 32 with CCRT. Each patient's head and neck area was evaluated by magnetic resonance imaging or computed tomography. Radiotherapy was administered at 2 Gy per fraction per day, Monday through Friday, for 35 fractions for a total dose of 70 Gy. Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two monthly cycles after radiotherapy. RESULTS: Patients who were treated with radiotherapy alone primarily had stage I disease, whereas none of those who were treated with CCRT had stage I disease (11 of 12 patients v none of 32 patients; P =.001). The locoregional control rate at 3 years for the radiotherapy group was 91.7% (median follow-up period, 34 months) and was 100% for the CCRT group (median follow-up period, 44 months) (P =.10). The 3-year disease-free survival rate in the radiotherapy group was 91.7% and was 96.9% in the CCRT group (P =.66). CONCLUSION: Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with CCRT. Stage II patients with a greater tumor burden treated with CCRT showed an equal disease-free survival, compared with stage I patients treated with radiotherapy alone. A prospective randomized trial is underway to confirm the role of CCRT in stage II NPC.     

The EORTC treatment of early stages of Hodgkin's disease: the role of radiotherapy

Since 1964, the European Organisation for Research and Treatment of Cancer has conducted three subsequent clinical trials on clinical Stages (CS) I + II Hodgkin's disease (HD) in which 1059 patients have been entered. The first trial compared regional radiotherapy (RT) with mantle field or inverted Y, versus the same RT followed by a weekly injection of vinblastine for 2 years. The relapse free survival (RFS) and overall survival (S) were higher in patients treated by RT and chemotherapy (CT). This benefit, however, was significant only in patients with a mixed cellularity histologic type. The second trial compared the therapeutic efficacy of splenic irradiation versus splenectomy and found that in both arms, RFS and S were identical. Moreover, it was found that splenic involvement was correlated with an increased incidence of relapse in extranodal sites and in non irradiated lymphatic areas. In this trial, CT was given only to patients with poor histologic types, mixed cellularity or lymphocytic depletion. In the third trial, staging laparotomy was performed only to further delineate a good prognostic group which could be treated by RT alone. In this limited treatment group, there was no difference in RFS and S between mantle field and mantle field + para-aortic RT. In the extensive treatment group, total nodal irradiation (TNI) was compared with RT + MOPP. The RFS was slightly lower in the TNI arm, but there was no significant difference in S. The data of the 3 trials underline the importance of prognostic factors in the choice of optimal treatment and show that their significance depends upon the type of treatment. Multivariate statistical analyses showed that the main prognostic factors, which can help to identify the subsets of patients who can be treated by RT alone, are (1) systemic symptoms and elevated erythrocyte sedimentation rate (ESR), (2) the number of involved lymphatic areas, and (3) staging laparotomy. Extended RT (mantle + para-aortic + spleen treatment) gives satisfactory results in patients without systemic symptoms and/or elevated ESR and one or two involved sites, whereas TNI or combined modality treatment becomes mandatory for patients with 3 or more involved sites or splenic involvement and/or systemic symptoms. With proper adjustment of the irradiated volume, a very large proportion of CS I + II patients can be best treated by RT alone.     

Survival of the older patient compared with the younger patient with Hodgkin's disease. Influence of histologic type, staging, and treatment

Age as an independent risk factor for survival of Hodgkin's disease (HD) was investigated using data for the 6345 patients in the American College of Surgeons, Patterns of Care Study. Patients were divided into those 15 to 34 years of age, and those older than 50 years. Older patients had higher rates of advanced stage and B symptoms (e.g., Stage IVB, 19.7% compared with 7.7%) and significantly higher rates of poor prognosis histologic types, odds ratio (OR) = 3.7. The older population with clinical stage (CS) I and II disease was also less likely to have received any of the selected staging procedures, bone marrow biopsy, lymphogram, or laparotomy (OR = 4.48). The two populations were equivalently understaged when CS was compared with pathologic stage (PS). In each category the older patients were more likely to have received no therapy; for PS I and II disease the OR for older patients compared with the younger patient was 2.14. When stratified by PS, B symptom status, histologic type, and treatment the older patients continued to show poorer 5-year survival by the life-table method. The authors' hypothesis--that older patients equivalently staged and treated would have no significant difference in long-term survival--was not substantiated by the data. However, in the analyses in which corrections for the known risk factors were made, the difference in survival was not as great as that in the crude, unstratified data. This study, as well as other recent studies utilizing smaller numbers of patients, finds age an independent predictor of poorer survival in HD patients.     

Cost-utility analysis of preoperative radiotherapy in patients with rectal cancer undergoing total mesorectal excision: a study of the Dutch Colorectal Cancer Group.

PURPOSE: To compare the societal costs and the (quality-adjusted) life expectancy of patients with rectal cancer undergoing total mesorectal excision (TME) with or without short-term preoperative radiotherapy (5 x 5 Gy). PATIENTS AND METHODS: We used a Markov model to project the clinical and economic outcomes of preoperative radiotherapy. Data on local recurrence rates, quality of life, and costs were obtained from the patients of a multicenter randomized clinical trial. In this trial, 1,861 patients with resectable rectal cancer from 108 hospitals were randomly assigned for TME surgery with or without preoperative radiotherapy. Outcome measures of the model were life expectancy, quality-adjusted life expectancy, lifetime costs per patient, and the incremental cost-effectiveness ratio. RESULTS: The base case model estimates that the loss of quality of life due to preoperative radiotherapy is outweighed by the gain in life expectancy. Life expectancy increases by 0.67 years; quality-adjusted life expectancy, by 0.39 years; and costs, by $9,800 per patient. The corresponding cost-effectiveness ratio is $25,100 per quality-adjusted life year. Sensitivity analyses indicate that the cost-effectiveness ratio remains acceptable under a wide range of assumptions. CONCLUSION: Assuming that the reduced local recurrence rate does lead to a survival advantage, the cost-utility analysis estimates that the improved survival outweighs the impaired quality of life and the increased costs. We conclude that short-term preoperative radiotherapy in patients with rectal cancer undergoing TME is both effective and cost-effective.     

原发扁桃体非霍奇金淋巴瘤的预后因素

目的：评价原发扁桃体非霍奇金淋巴瘤（NHL）的肿瘤侵犯范围（T分期）和国际预后指数（IPI）的预后价值,并对早期患者提出治疗建议。方法：回顾分析306例原发扁桃体NHL,根据Ann Arbor分期,I期35例,II期178例,Ⅲ期49例,Ⅳ期44例,根据1997年AJCC TNM分期标准,TI 29例,T2 142例,T3 117例,T4 18例,I期单纯放射治疗12例,综合治疗23例,Ⅱ期单纯放射治疗57例,单纯化疗2例,综合治疗119例,Ⅲ,Ⅳ期以化疗为主,结果：T1,T2,T3和T4的5年癌症相关生存率（CSS）分别为73．8％,59．0％,56．5％和26．5％（P＜0．05）,IP1评分0分,1分和2或3分的5年CSS分别为69．9％,49．0％和25．0％（P＜0．01）,II期单纯放疗和综合治疗的5年无瘤生存率（DFS）分别为46．2％和60．4％（P＜0．05）,多因素分析证明,影响预后的因素有一般状态,B症状,Ann Arbor分期,T分期和IPI,结论：原发肿瘤T分期和IPI是扁桃体NHL重要的预后因素,综合治疗改善了II期扁桃体NHL的DFS。     

Radiotherapy for stage I Hodgkin's disease: 20 years experience at St Bartholomew's Hospital

One hundred and one consecutive patients with newly diagnosed stage I Hodgkin's disease (HD) received treatment at St Bartholomew's Hospital, between 1968 and 1987, with a median follow-up of 12 years. Eleven patients have been excluded from detailed analysis because they either received involved field radiotherapy (RT) or radiotherapy with chemotherapy or were lost to follow-up. Actuarial analysis predicts 78% to be alive and without relapse of Hodgkin's disease at 15 years. Ninety evaluable patients (clinical stage (CS) 24; pathological stage (PS) 66) received either mantle or inverted 'Y' RT and form the basis of this analysis. The median age was 33 years (63 men, 27 women). Histology at presentation was nodular sclerosing (39), lymphocytic predominant (27) or mixed cellularity (24). The presenting site was neck (78), axilla (6) groin (4) and mediastinum (2). Complete remission was achieved in all evaluable patients, the actuarial proportion in remission being 75% at 15 years. Factors predictive of a prolonged remission were pathological staging versus clinical staging (P = 0.02) and lymph node size less than 3 cm (P = 0.04). Actuarial overall survival in these 90 patients was 75% at 15 years and none of the above factors correlated with survival. Relapse of HD has occurred in 18 patients (5 within RT field, 10 without and 3 in both). Second remission was achieved in 15/18. The actuarial rate of second remission and survival was 40% at 10 years. Sixteen patients have died, 7 of Hodgkin's disease, 7 of unrelated causes and 2 of second malignancy. A further 3 patients who developed second malignancy are still alive. At 15 years the actuarial mortality related to HD was 12%. These results confirm the importance of long follow up to assess the efficacy of primary therapy.     

Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease.

PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.