Early-stage mantle cell lymphoma: a retrospective analysis from the International Lymphoma Radiation Oncology Group (ILROG).

BACKGROUND: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. PATIENTS AND METHODS: In this 13-institution study, we examined outcomes among 179 patients with early-stage (stage I or II) MCL in an attempt to identify prognostic factors that influence treatment selection and outcome. Variables examined included clinical characteristics, treatment modality, response to therapy, sites of failure, and survival. RESULTS: Patients were predominantly male (78%) with head and neck being the most common presenting sites (75%). Most failures occurred outside the original disease site (79%). Although the administration of radiation therapy, either alone or with chemotherapy, reduced the risk of local failure, it did not translate into an improved freedom from progression or overall survival (OS). The treatment outcomes were independent of treatment modality. The 10-year OS for patients treated with chemotherapy alone, chemo-radiation therapy and radiation therapy alone were 69%, 62%, and 74% (P = 0.79), and the 10-year freedom from progression were 46%, 43%, and 31% (P = 0.64), respectively. CONCLUSION: Given the excellent OS rates regardless of initial therapy in patients with early-stage MCL, de-intensified therapy to limit treatment-related toxicity is a reasonable approach.

Paediatric primary cutaneous marginal zone B-cell lymphoma: does it differ from its adult counterpart?

BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (PCMZL) has rarely been reported in patients younger than 20 years. OBJECTIVES: To report our experience with PCMZL in the paediatric/adolescent age group. METHODS: Medical records of patients diagnosed with PCMZL before age 20 years and managed at two cutaneous lymphoma clinics in the U.S.A. and Israel from 1992 to 2015 were reviewed. RESULTS: The study group included 11 patients (six girls; median age 16 years, range 6-19·5); 10 had generalized/multifocal (T3) and one had regional/localized (T2) disease. Lesions were located on the limbs in all patients and the trunk in six; two had facial lesions. Staging in all but one was based on whole-body computed tomography or positron emission tomography. Initial management in most patients included nonradiation modalities: one patient with localized disease received intralesional steroids; six patients with multifocal disease received the following: topical/intralesional steroids (n = 3); excision (n = 2); 'watch and wait' (n = 1). No extracutaneous progression was noted during a median follow-up of 5·5 years (mean 7·5, range 0·5-14). At present, five patients are in complete remission. CONCLUSIONS: Based on our data (largest series in the literature with the longest follow-up), the clinicopathological presentation and course of PCMZL in the paediatric/adolescent age group are similar to those in adults. Given the indolent course and the long life expectancy of these young patients, the cumulative risk of imaging studies and the age-related potential toxicity of treatment, especially radiation, should be taken into consideration.

Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma.

BACKGROUND: The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs. RESULTS: One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003). CONCLUSION(S): BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial.

INTRODUCTION: To assess the efficacy of an abbreviated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS: with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the G4 study. Stanford V chemotherapy was administered for 8 weeks followed by radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated. RESULTS: All 87 enrolled patients completed the abbreviated regimen. At a median follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively. Therapy was well tolerated with no treatment-related deaths. CONCLUSIONS: Mature results of the abbreviated Stanford V regimen in nonbulky early-stage HL are excellent and comparable to the results from other contemporary therapies.

Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy: a retrospective, multi-centre, International Extranodal Lymphoma Study Group study.

BACKGROUND: We evaluated the long-term results of radiotherapy for patients with gastric marginal zone lymphoma (GMZL). PATIENTS AND METHODS: We carried out a retrospective, multi-centre study of patients with low-grade GMZL treated by radiotherapy between 17 July 1981 and 25 March 2004. RESULTS: There were 102 eligible patients. Fifty-eight patients were previously untreated and 44 had recurrent/residual disease after prior treatment (HP eradication, chemotherapy and surgery in 35, 9 and 8 patients, respectively, and 7 had >1 prior therapy). Radiation fields included the stomach /involved nodes in 61 patients and whole abdomen in 41. The median radiotherapy dose to stomach was 40 Gy (range 26-46 Gy) in a median 22 fractions. With a median follow-up after radiotherapy of 7.9 years (range 0.3-24 years), 10- and 15-year freedom from treatment failure (FFTF) was 88% (95% CI 82%-95%). Risk factors for TF were a large-cell component (P = 0.036) and an exophytic growth pattern (P = 0.042). Radiotherapy field size, radiotherapy dose, and failure of prior therapy were not associated with inferior FFTF. Ten-year overall survival was 70% (95% CI 60%-82%). CONCLUSIONS: Radiotherapy achieves cure for the majority of patients with low-grade GMZL, including patients who have had prior therapy. Several features may predict a poorer outcome.

Outcomes of adults with lymphoma treated with nonmyeloablative TLI-ATG and radiation boost to high risk or residual disease before allogeneic hematopoietic cell transplant.

We evaluated the impact on survival of antithymocyte globulin conditioning (TLI-ATG) with radiation (RT) boost to high risk or residual disease before allogeneic hematopoietic cell transplant (allo-HCT) for adults with lymphoma (excluding mycosis fungoides and low-grade NHL other than SLL/CLL). Of 251 evaluable patients, 36 received an RT boost within 3 months of allo-HCT at our institution from 2001 to 2016. At the time of TLI-ATG, patients who received boost vs no boost had a lower rate of CR (11% vs 47%, p = 0.0003), higher rates of bulky disease (22% vs 4%, p < 0.0001), extranodal disease (39% vs 5%, p < 0.0001), and positive PET (75% vs 28%, p < 0.00001). In the boost group, the median (range) largest axial lesion diameter was 5.2 cm (1.8-22.3). Median follow-up was 50.2 months (range: 1-196). There was no significant difference in OS, time to recurrence, or time to graft failure with vs without boost. A trend toward higher percent donor CD3+ chimerism was seen with vs without boost (p = 0.0819). The worst boost-related toxicity was grade 2 dermatitis. RT boost may help successfully mitigate the risk of high risk or clinically evident residual disease in adults with lymphoma undergoing allo-HCT.

A Step Toward Making VMAT TBI More Prevalent: Automating the Treatment Planning Process.

PURPOSE: Our purpose was to automate the treatment planning process for total body irradiation (TBI) with volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: Two scripts were developed to facilitate autoplanning: the binary plug-in script automating the creation of optimization structures, plan generation, beam placement, and setting of the optimization constraints and the stand-alone executable performing successive optimizations. Ten patients previously treated in our clinic with VMAT TBI were used to evaluate the efficacy of the proposed autoplanning process. Paired t tests were used to compare the dosimetric indices of the produced auto plans to the manually generated clinical plans. In addition, 3 physicians were asked to evaluate the manual and autoplans for each patient in a blinded retrospective review. RESULTS: No significant differences were observed between the manual and autoplan global Dmax (P < .893), planning target volume V110% (P < .734), kidneys Dmean (P < .351), and bowel Dmax (P < .473). Significant decreases in the Dmean to the lungs and lungs-1cm (ie, lungs with 1-cm inner margin) volumes of 5.4% ± 6.4% (P < .024) and 6.8% ± 7.4% (P < .017), respectively, were obtained with the autoplans compared with the manual plans. The autoplans were selected 77% of the time by the reviewing physicians as equivalent or superior to the manual plans. The required time for treatment planning was estimated to be 2 to 3 days for the manual plans compared with approximately 3 to 5 hours for the autoplans. CONCLUSIONS: Large reductions in planning time without sacrificing plan quality were obtained using the developed autoplanning process compared with manual planning, thus reducing the required effort of the treatment planning team. Superior lung sparing with the same target coverage and similar global Dmax were observed with the autoplans as compared with the manual treatment plans. The developed scripts have been made open-source to improve access to VMAT TBI at other institutions and clinics.

Autologous mixed lymphocyte reaction in patients with Hodgkin's disease. Evidence for a T cell defect.

The proliferative response of T lymphocytes cultured with autologous non-T lymphocytes is known as the autologous mixed lymphocyte reaction (MLR). This reaction can be demonstrated reproducibly in healthy individuals and has been shown to generate specific cytotoxic T cells, as well as T cells that regulate antibody synthesis and cell-mediated immunity. In this study, we demonstrate that the autologous MLR is impaired or absent in most patients with Hodgkin's disease regardless of age, sex, pathologic stage, or histologic classification. In 64 patients, the mean autologous MLR was 3,084+/-1,878 cpm compared to 16,552+/-6,532 in 29 healthy donors. A defect in autologous MLR was observed in newly diagnosed patients before the initiation of therapy, but was also found in patients without evidence of recurrent disease up to 15 yr after treatment. These findings could not be explained by abnormal kinetics or poor viability of stimulator or responder cells. The possibility that suppressor cells are responsible for the reduction of T cell autoreactivity was examined by comparing the autologous MLR of a healthy HLA-identical sibling in the presence and absence of T or non-T cells of an affected sibling. No inhibitory effects were observed. Similarly, substitution of patient plasma for pooled AB serum failed to inhibit the autologous responses of normal donors. Increasing the number of responder T cells in the culture or removing adherent cells from the stimulator population enhanced autoreactivity in some patients, indicating that the defect is not absolute. In two families, T cells of healthy HLA-A, B, and DR-identical siblings of patients responded normally to the non-T cells of their affected siblings, whereas patients' T cells failed to respond both to their own stimulator cells and those of their healthy HLA-identical siblings. These data indicate that the impairment of autologous MLR in some patients is due to a reduction or dysfunction of responder T cell activity and not to a defect of autologous stimulator cells.

Breast cancer after treatment of Hodgkin's disease.

BACKGROUND: Most studies of survivors of Hodgkin's disease have shown a low risk for subsequent breast cancer, even though much lower doses of radiation than those used for Hodgkin's disease have been shown to induce breast cancer in other settings. PURPOSE: This study quantifies the risk of breast cancer following Hodgkin's disease treatment according to age at treatment and type of treatment. METHODS: To evaluate the risk of breast cancer from irradiation, we reviewed records of 885 women treated for Hodgkin's disease between 1961 and 1990 (mean follow-up, 10 years). Risks for breast cancer incidence and mortality were calculated by comparison with expected rates for a general female population matched by age and race. RESULTS: Twenty-five patients have developed invasive breast cancer, yielding a relative risk (RR) of 4.1 (95% confidence interval [CI] = 2.5-5.7). An additional patient developed multifocal carcinoma in situ. Age at irradiation strongly influenced risk: RR was 136 for women treated before 15 years of age (95% CI = 34-371). RR declined with age at irradiation (P for trend < .0001), but the elevation remained statistically significant for subjects less than 30 years old at the time of irradiation (for those 15-24, RR = 19 [95% CI = 10.3-32]; for those 24-29, RR = 7 [95% CI = 3.2-14.4]). In women above 30 years of age, the risk was not elevated (RR = 0.7; 95% CI = 0.2-1.8). Risk of breast cancer increased significantly with time since treatment (P for trend < .0001). The RR was 2.0 (95% CI = 1.0-3.5) with follow-up under 15 years and 13.6 (95% CI = 7.9-18.2) with follow-up equal to or exceeding 15 years. The addition of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy to irradiation increased the risk within the first 15 years. Most breast cancers (22 of 26) arose within or at the margin of the radiation field and were infiltrating ductal carcinomas. Stage distribution and outcome suggest that the increased incidence was not solely attributable to vigilant screening. RR of death from breast cancer was 5.1 (95% CI = 2.2-10.0). CONCLUSIONS: Women treated for Hodgkin's disease with radiation before 30 years of age are at markedly increased risk for breast cancer, with risk increasing dramatically more than 15 years after therapy. IMPLICATIONS: The high RR for development of breast cancer in women exposed to therapeutic radiation under 30 years of age raises important issues about optimal treatment strategies for patients with Hodgkin's disease, breast cancer, and other cancers.

Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University.

PURPOSE: To evaluate retrospectively the results of radiotherapy for 177 patients with stage I (n = 73 [41%]) and II (n = 104 [59%]) follicular small cleaved-cell and follicular mixed small cleaved-cell and large-cell non-Hodgkin's lymphoma (NHL) treated in the Department of Radiation Oncology, Stanford University between 1961 and 1994. PATIENTS AND METHODS: Histology was follicular small cleaved-cell in 101 (57%) cases and follicular mixed small cleaved-cell and large-cell in 76 (43%). Forty-five patients (25%) had staging laparotomy; 34 (19%) had extranodal involvement. All patients had received radiotherapy, either to one side of the diaphragm (involved or extended field) or to both sides (total lymphoid irradiation [TLI] or subtotal lymphoid irradiation [STLI]. Radiotherapy doses ranged from 35 to 50 Gy. RESULTS: The median follow-up duration was 7.7 years. The longest follow-up duration was 31 years. Actuarial survival rates at 5, 10, 15, and 20 years were 82%, 64%, 44%, and 35%, respectively. The median survival time was 13.8 years. At 5, 10, 15, and 20 years, 55%, 44%, 40%, and 37% of patients, respectively, were relapse-free. Only five of 47 patients who reached 10 years without relapse subsequently developed recurrence. Survival and freedom from relapse (FFR) were significantly worse for older patients. Relapse rates were lower following treatment on both sides of the diaphragm or staging laparotomy. Univariate analysis showed that youth and staging laparotomy were associated with significantly better survival and that FFR was better following treatment on both sides of the diaphragm or laparotomy. CONCLUSION: Radiotherapy remains the treatment of choice for early-stage low-grade follicular lymphomas. Patients who have remained free of disease for 10 years are unlikely to relapse.

Stage I to IIB Hodgkin's disease: the combined experience at Stanford University and the Joint Center for Radiation Therapy.

The treatment records of 180 patients with pathological stage (PS) IB to IIB Hodgkin's disease treated at Stanford University Medical Center (SUMC) or the Joint Center for Radiation Therapy (JCRT) were reviewed. Pretreatment characteristics were analyzed to assess their influence on survival and freedom from relapse (FFR). The two most important disease characteristics predictive of relapse were the number and type of B symptoms present and the mediastinal mass ratio (MMR). Patients with both fevers and weight loss had a 7-year survival and FFR of only 57% and 48%, respectively. The poor prognosis in this group was apparent for treatment with either radiation (XRT) alone or combined modality therapy (CMT). Patients with night sweats only had no adverse effect of B symptoms on outcome. Patients with a MMR greater than 1/3 had a 7-year FFR of only 58% after XRT, but 79% after CMT (P = .12). The 7-year survivals for these patients were 85% and 88%, respectively. CMT improved the FFR of the entire group of 180 patients when compared with XRT (7-year FFR 86% and 74%, respectively, P = .02); however, survival in the two treatment groups was similar (88% and 89%). Among patients treated with radiation alone, there was a similar survival and FFR irrespective of whether pelvic irradiation was included in the initial treatment fields.

Subdiaphragmatic Hodgkin's disease: laparotomy and treatment results in 49 patients.

The clinical records of 1,616 patients with previously untreated Hodgkin's disease were reviewed. Forty-nine of these patients (3%) presented with disease limited to sites below the diaphragm and underwent laparotomy as part of their staging evaluation. The clinical and histological characteristics of this group of patients with subdiaphragmatic Hodgkin's disease are compared with those who presented with supradiaphragmatic disease. Splenectomy in 47 patients revealed splenic involvement in 16 (39%), and bulky splenic involvement (more than five gross nodules) in ten (24%). The final pathological stage (PS) distribution was PS I = 8, PS II = 37, PS IV = 4. No clinical stage (CS) IA patients and only two of 20 patients with negative paraaortic nodes on lymphogram had splenic involvement in contrast to eight of nine CS IIB patients. Freedom from relapse and survival were similar to patients with equivalent stage supradiaphragmatic disease. Splenic involvement and bulky splenic involvement were associated with a significantly decreased survival. Twelve out of 44 PS IA to IIB patients relapsed. In eight of these 12 patients, relapse was limited to sites above the diaphragm and another two patients relapsed both above and below the diaphragm. Patients who received total lymphoid irradiation were less likely to relapse above the diaphragm than patients who received no supradiaphragmatic irradiation. We recommend that CS IA and IIA patients with subdiaphragmatic disease undergo staging laparotomy and receive supradiaphragmatic irradiation as part of their treatment. Laparotomy may not be necessary for CS IIB patients who are at high risk for splenic disease if chemotherapy is planned as part of their treatment program.

Radiotherapy with curative intent: an option in selected patients relapsing after chemotherapy for advanced Hodgkin's disease.

Thirteen patients who had relapsed or failed to obtain a complete remission after combination chemotherapy for the treatment of advanced Hodgkin's disease were treated with subtotal or total lymphoid irradiation with curative intent. Twelve of the 13 patients achieved a complete response (CR). Five of the 12 CRs subsequently relapsed at 3, 9, 9, 12, and 19 months. One patient died of leukemia 11 months following radiotherapy. The actuarial relapse-free survival at 1 year was 60%, and six patients (50%) remain disease-free with a median follow-up of 34 months (range, 10 to 115 months) following the completion of radiotherapy. Patients who failed to obtain a CR to their initial chemotherapy, whose chemotherapy CR was of short duration, or who relapsed initially in extranodal sites, tended to have a worse outcome with radiotherapy. Patients who had long disease-free intervals after initial chemotherapy or relapsed only in nodal sites tended to do relatively well. Radiation therapy was well tolerated with no major toxicity. Potentially curative radiation therapy should be considered an option in the management of selected patients who relapse following combination chemotherapy for advanced Hodgkin's disease.

Mycosis fungoides: management with topical nitrogen mustard.

The technique of treatment, response rate, freedom from relapse, survival, and complications of therapy in 123 patients treated with topical nitrogen mustard (HN2) for cutaneous mycosis fungoides (MF) at Stanford University Medical Center are reviewed. Patients were treated with HN2 in an aqueous or ointment base with equal efficacy. Response rates depended on the extent of skin involvement. In limited plaque (T1) disease, complete and overall response rates were 51% and 88%, respectively, while in generalized plaque (T2) disease they were 26% and 69%. No patients with tumorous involvement (T3) achieved complete skin clearance and all 13 of these patients developed progression of disease. Only two of nine patients with erythrodema (T4) achieved a complete response (CR), and both later relapsed. After achieving a CR, 40% of patients with T1 disease and 60% with T2 disease later relapsed; however, subsequent therapies, including repeat courses of topical HN2, often were successful in achieving later skin clearance. Overall, 42% of T1 patients and 31% of T2 patients were without evidence of MF at last follow-up. When death occurred, it was usually unrelated to MF in the T1 group. However, half of the deaths of patients with T2 disease were attributable to MF. Among the 22 patients with T3 or T4 disease, 80% of deaths were attributable to MF. The most common complication observed was a cutaneous hypersensitivity reaction, which occurred much more commonly with the aqueous than the ointment preparation. Fourteen patients (11%) developed subsequent cutaneous malignancies.

Solitary plasmacytoma of bone: treatment, progression, and survival.

Twenty patients with solitary plasmacytoma of bone were treated by radiation therapy. Local control was achieved in 19 and most patients developed systemic myeloma. To evaluate disease progression, 65 patients, including 45 from published series, were analyzed. Younger patients seemed less likely to progress (P = .06), but other clinical characteristics including site of involvement and paraprotein status did not influence progression. After dissemination, patients had a clinical course similar to patients with stage I myeloma, with a median survival of 47 months. Overall, patients with solitary plasmacytoma of bone had an indolent course of disease, with a median survival of 10.7 years and a 5-, 10-, and 20-year survival of 75%, 52%, and 37%, respectively.

Vinblastine, bleomycin, and methotrexate: an effective adjuvant in favorable Hodgkin's disease.

Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or female fertility. Selected pulmonary functions are reduced early after IF plus VBM to a greater degree than with irradiation of the mediastinum alone, but the differences are modest. Based upon our current numbers and follow-up, we can be 90% confident that VBM as an adjuvant to irradiation in favorable Hodgkin's disease is as effective, or even superior, to MOP(P) chemotherapy. Because of its lesser toxicity, adjuvant VBM may have a broader role in the management of Hodgkin's disease.

Detection of relapse in early-stage Hodgkin's disease: role of routine follow-up studies.

PURPOSE: To examine the costs and benefits of routine follow-up evaluation in patients treated with radiation therapy for early-stage Hodgkin's disease. PATIENTS AND METHODS: We retrospectively examined patterns of follow-up evaluation and methods of relapse detection among 709 patients with stage I and II Hodgkin's disease treated with primary radiotherapy between 1969 and 1994. We determined the probability of relapse detection for seven routine follow-up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of survival following salvage therapy. RESULTS: Relapse has occurred in 157 patients (22%) at a median 1.9 years (range, 0 to 13 years) posttreatment. Relapse was suspected primarily by history (Hx) in 55% of patients, physical examination (PE) in 14%, chest x-ray (CXR) in 23%, and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study. The rate of relapse detection was highest for a combination of Hx and PE (78 of 10,000 examinations) followed by CXR (26 of 10,000 examinations). The projected charges (1995 dollars) per relapse detected by routine follow-up Hx and PE were $11,000 compared with $68,000 for CXR and $142,000 for KUB. The 10-year actuarial survival rate following salvage therapy was 65% overall, 65% for patients in whom relapse was detected by Hx or PE, and 69% for patients in whom relapse was detected by radiographs (P = not significant). CONCLUSION: The majority of relapses occurred within 5 years of treatment and were identified by Hx and PE. CXR was useful during the first 3 years of follow-up evaluation. KUB, CBC, and laboratory studies accounted for nearly half of all follow-up charges and rarely led to the detection of relapse. Their routine use as a method of relapse detection is questionable. In general, the method of relapse detection did not have a significant impact on the likelihood of successful salvage therapy.

Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease.

Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value.

Follicular and diffuse mixed small-cleaved and large-cell lymphoma--a clinicopathologic study.

The clinical records and initial biopsy materials from 76 patients with mixed small-cleaved and large-cell lymphoma containing both a follicular and diffuse architectural pattern were reviewed. The characteristics of this group, treated at Stanford University Medical Center (SUMC) between 1963 and 1983, are described. The 5-year actuarial survival and freedom from progression are 70% and 27.5%, respectively. Classification according to the degree of follicularity indicated that patients with focally follicular areas (ie, less than 25% of the histologic section) have a significantly worse freedom from progression and overall survival at 5 years compared with those patients with a predominantly follicular architecture (ie, greater than 50% follicular areas). Based on our analysis, we feel that the degree of follicularity is an important prognostic factor and that mixed lymphoma patients with only focally follicular areas behave more like an intermediate-grade lymphoma and should be treated aggressively.

Stage IIB Hodgkin's disease: the Stanford experience.

Between 1968 and 1982, 126 patients with pathologic stage (PS) IIB Hodgkin's disease were treated at Stanford University with either irradiation alone or irradiation combined with chemotherapy. Actuarial survival and freedom from relapse rates at 10 years for the overall group were 81% and 74% respectively, with no statistically significant difference between the treatment approaches. The impact of the severity and number of constitutional (B) symptoms, as defined by the Ann Arbor Conference, was analyzed. Patients who presented with all three B symptoms had significantly poorer survival and freedom from relapse compared with those patients with only one or two B symptoms (for survival differences, P = .005 and .007; for freedom from relapse differences, P = .002 and .04). Male sex was the only other prognostic factor that correlated with a poor outcome. At 10 years, the survival rate was 66% for males v 84% for females (P = .01), and the freedom from relapse rate was 75% for males v 89% for females (P = .02). The presence of extralymphatic sites of involvement, age greater than 40, or involvement of greater than three lymphoid sites had no significant adverse effect on either freedom from relapse or survival. Patients with large mediastinal masses treated with irradiation alone had a 10-year freedom from relapse rate of 54% v 81% for those treated with combined-modality therapy (P = .15), but there was no significant difference in survival rates (85% for irradiation alone v 71% for combined modality therapy). Treatment recommendations for stage IIB Hodgkin's disease are discussed.