Patients' expectations and experiences of rehabilitation following lung transplantation.

INTRODUCTION: Exercise rehabilitation is a key element of care following lung transplantation; however, little is known about the patients' experience of rehabilitation, or whether it meets the needs of this complex patient group. This qualitative study explored patients' expectations of a supervised exercise rehabilitation program following lung transplantation. METHODS: Participants undertook two semi-structured interviews, one before and one after the rehabilitation program. Interviews were digitally recorded, and themes were developed using line-by-line iterative thematic analysis and grounded theory. RESULTS: Eighteen adults (11 females) with mean age of 52 participated in a mean of 26 sessions of exercise training. Themes were (i) desire for normalcy including resuming family roles and performing everyday activities; (ii) the importance of rehabilitation as the mechanism for how this transformation occurred; (iii) the benefits of exercising in a group setting; and (iv) the limitations on rehabilitation that were imposed by comorbidities, either existing pre-transplant or occurring as a postoperative sequelae. CONCLUSION: Post-transplant exercise rehabilitation was perceived as a highly valuable tool that assisted recipients to return to "normal life." Group exercise was motivational, offered peer support, and therefore was advantageous to assist patients to achieve their desired physical performance level following transplantation.

Incidence of second cancers in patients treated for Hodgkin's disease.

BACKGROUND: Numerous studies of treatment for Hodgkin's disease have demonstrated large increases in the incidence of leukemia in the early years following chemotherapy, although the duration of effect and the specific agents involved are not well understood. Also, some, but not all, studies have indicated that the incidence of certain solid tumors increases following treatment for Hodgkin's disease. PURPOSE: We studied the association between treatment for Hodgkin's disease and the incidence of second cancers. METHODS: We conducted a study within a cohort that included 10,472 patients from 14 cancer centers in the United States and Canada who were first diagnosed as having Hodgkin's disease at some point from 1940 through 1987. Discounting the 1st year after diagnosis, the average length of follow-up was 7.1 years per subject. RESULTS: We observed 122 leukemias and 438 solid tumors. The relative risk (RR) of leukemia following chemotherapy, compared with no chemotherapy, was 14 (95% confidence interval [CI] = 5.6-35). Increased risks of leukemia were observed after treatment with chlorambucil (RR = 2.0; 95% CI = 1.1-3.6), procarbazine (RR = 4.9; 95% CI = 2.6-9.1), vinblastine (RR = 1.7; 95% CI = 1.1-2.8), and a group of rarely used drugs that included methotrexate, vindesine, etoposide, and 22 others (RR = 3.8; 95% CI = 1.9-7.4). RRs were also estimated for various combinations of drugs, including MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) (RR = 5.9; 95% CI = 2.9-12) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (RR = 1.5; 95% CI = 0.7-3.4). The RR of leukemia associated with splenectomy was 1.6 (95% CI = 1.0-2.5). The RR of solid tumors following chemotherapy was 1.4 (95% CI = 1.1-1.8). For the group of rarely used drugs, the RR of solid tumors was 3.1 (95% CI = 1.7-5.8). Chemotherapy was associated with an increased risk of cancers of the bones, joints, articular cartilage, and soft tissues (RR = 6.0; 95% CI = 1.7-20), and cancers of the female genital system (RR = 1.8; 95% CI = 1.1-3.2). In patients followed for 10 or more years after radiotherapy, increased risks were found for cancers of the respiratory system and intrathoracic organs (RR = 2.7; 95% CI = 1.1-6.8) and for cancers of the female genital system (RR = 2.4; 95% CI = 1.1-5.4). CONCLUSIONS: Procarbazine, chlorambucil, and vinblastine are associated with increased leukemia risk. Combination drug regimens have leukemogenic effects estimated as the product of RRs for individual drugs. Chemotherapy and radiotherapy increase the risk of selected solid tumors, and the effect of chemotherapy on solid tumor risk is weaker than the leukemogenic effect. IMPLICATIONS: Without doubt, the benefits of treatment of Hodgkin's disease outweigh the risk of a subsequent malignancy, but data on the carcinogenic effects of radiation and drugs beyond 10 years after treatment continue to be sparse, and future analyses should be directed at long-term survivors.

Stomach conservation in stages IE and IIE gastric non-Hodgkin's lymphoma.

Thirty-four patients with stages IE and IIE gastric lymphoma were treated with chemotherapy and radiotherapy combinations without stomach resection. In 20 patients, the diagnosis was established by endoscopic biopsy only; the other 14 had laparotomy and biopsy. No patient had a gastrectomy before treatment. Nineteen patients had stage IE disease and 15 had stage IIE. Lymphoma diagnoses were: diffuse large-cell, 26; immunoblastic, three; diffuse well-differentiated, three; nodular mixed, one; and unclassified, one. The treatment plan was to deliver an initial four cycles of chemotherapy, followed by radiotherapy, and finally, more chemotherapy. Thirty-three patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Four patients with stage IIE disease received cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED). Twenty-three patients (68%) never had a relapse. Three patients had successful salvage therapy, one for local recurrence and two for tumor dissemination. Five patients died of recurrent abdominal disease, and one died of tumor dissemination. Two died of treatment-related complications, one of sepsis during treatment with CMED and one of bleomycin-induced lung fibrosis. No patient developed stomach perforation or bleeding as a result of chemotherapy or radiotherapy. Twenty-four of the 26 surviving patients were able to retain their stomachs. One patient required a gastrectomy for progressive disease during chemotherapy, and another required a subtotal gastrectomy for relief of an obstruction caused by cicatrization. These data show that surgery is not a necessary procedure in gastric lymphoma. Favorable results can be achieved by combining effective chemotherapy and local radiation.

Two cycles of MOPP and radiotherapy for stage III1A and stage III1B Hodgkin's disease.

One hundred two adult patients with stage III1A (76 patients) and stage III1B (26 patients) Hodgkin's disease were treated with two cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and radiotherapy (XRT) between 1970 and 1984. Sixty-four of the patients were treated between 1970 and 1978 with two cycles of MOPP and XRT to the mantle, upper abdomen, and pelvis. The remaining 38 patients were treated from 1978 to 1984 with a modification of the protocol in which pelvic XRT was omitted and low-dose whole-lung XRT was administered to patients with unfavorable mediastinal disease. The 10-year actuarial freedom-from-progression (FFP) and determinate survival rates at a mean follow-up of 93 months were 84% and 86% for stage III1 disease, 86% and 84% for stage III1A disease, and 78% and 91% for stage III1B disease. Three patients died of treatment-related toxicities without evidence of Hodgkin's disease, two died of complications of myelosuppression and one of acute nonlymphocytic leukemia (ANLL). Neither FFP nor determinate survival rates were significantly influenced by B symptoms, unfavorable mediastinal disease, histologic subtype, extent of abdominal disease, the omission of pelvic XRT, the use of whole-lung XRT, or the number of splenic nodules. Patients 40 years of age or older had a 73% determinate survival rate at 10 years compared with 88% for patients younger than 40 years (P = .01). This survival difference was due to treatment-related toxicity in the older group. This study indicates that two cycles of MOPP and XRT to the mantle and upper abdomen is as effective as more intensive treatment for all patients with stage III1 Hodgkin's disease. This treatment program can preserve fertility and has had only a 1% actuarial incidence of ANLL at 15 years.

Stage IV diffuse large-cell lymphoma: a long-term analysis.

A long-term analysis of the clinical outcome of previously untreated adult patients who presented with stage IV diffuse large-cell lymphoma at diagnosis was performed to identify possible prognostic factors. Sixty-one patients were seen between 1974 and 1981; all were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin followed by cyclophosphamide, vincristine, prednisone, and bleomycin for a total of one year. Overall five-year survival was 48.5%, with a median follow-up of 53 months. Of the 56 patients evaluable for remission status, 41 achieved a complete remission, and 27 are alive and disease free. Clinical factors of prognostic importance for survival included age, constitutional symptoms, lactate dehydrogenase (LDH) level, presence of mediastinal disease, large-cell infiltration of bone marrow, and number of extranodal sites of disease. The proportional hazards model then identified age, number of extranodal sites, and, to a lesser extent, serum LDH level as independent risk factors for survival. Four distinct patient risk groups were identified using these three factors. Younger patients with only one extranodal site of disease and normal LDH levels responded well on this therapy, with 100% alive at five years. In contrast, survival was less than 30% at five years for patients in the lowest risk group. There were 11 relapses; LDH level, constitutional symptoms, and mediastinal disease predicted for relapse. Knowledge of these risk factors permits individualization of treatment planning and allows more meaningful comparisons with the results of treatment studies using other intensive regimens.

Follicular large cell lymphoma: analysis and prognostic factors in 62 patients.

Sixty-two patients with follicular large cell lymphoma were treated between 1973 and 1981. The overall median survival was 78 months with a five-year survival of 62%. The complete remission rate was 76%, with a median relapse-free interval of 72 months for responders. Complete remission produced a significantly longer survival than partial response and failure. Patients who tolerated therapy with an intensive doxorubicin-containing regimen had a significantly longer relapse-free interval and survival. Patients with stage I-II disease treated with radiation therapy alone had a higher relapse rate than those treated with radiation and combination chemotherapy. The addition of radiation therapy to combination chemotherapy in stage III-IV disease decreased the incidence of relapse at irradiated sites, but did not translate into improved survival. Pretreatment prognostic factors associated with poor response were thrombocytosis and stage III-IV disease; those associated with shortened survival were thrombocytosis, elevated lactic dehydrogenase level, stage III-IV disease, and bulky abdominal disease. Follicular large cell lymphoma is an aggressive lymphoma. Treatment should be curative in intent, and should include intensive combination chemotherapy even in stage I-II disease. Knowledge of important prognostic factors can be useful for analysis of future trials and planning therapeutic strategies.

Tumor burden assessment and its implication for a prognostic model in advanced diffuse large-cell lymphoma.

Previously untreated adult patients who presented with advanced diffuse large-cell lymphoma (DLCL) at diagnosis were studied to identify possible prognostic factors. One hundred five patients were seen between 1974 and 1981; 45 patients were stage III and 60 patients were stage IV. All patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Stage III patients also received radiation therapy alternated with chemotherapy. Overall survival was 50% at 5 years and 43% at 8 years. Seventy-four patients achieved a complete remission (CR) and 37 are alive and disease-free with a median follow-up of 72 months. There was no difference in clinical outcome between stage III and stage IV. However, a proportional hazards model identified lactic dehydrogenase (LDH) level and tumor burden, among all clinical factors studied, as independent risk factors for survival. These two factors were also important for achievement of remission and relapse-free survival. Three distinct patient risk groups were identified with 5-year survival rates of 87%, 48%, and 20%, respectively. The measure of tumor burden proposed herein, along with LDH level, can be used for developing treatment programs, and for meaningful comparison of different treatment regimens, as well as assessment of prognosis.

Stage III follicular lymphoma: durable remissions with a combined chemotherapy-radiotherapy regimen.

From 1975 to 1982, 74 patients with stage III follicular lymphoma were treated with a combined modality protocol which included chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and radiotherapy to involved regions. This program resulted in a complete remission (CR) rate of 81%, a 5-year survival of 75%, and 5-year relapse-free survival (RFS) of 52% for all patients. Analysis of potential factors affecting treatment outcome revealed a significantly better CR rate for patients with small cleaved cell type (97%) than for patients with mixed (73%) or large-cell (57%) histologies. The 5-year survival was significantly better for patients with small cleaved (91%) and mixed (84%) cell types than for large cell (40%). In addition, bulky abdominal disease and elevated serum lactate dehydrogenase (LDH) were significant adverse prognostic factors for CR and for survival. Toxicity was moderate. No secondary leukemias have occurred. This combined modality regimen resulted in prolonged remission and potential cure for over half of patients who achieved CR, and is particularly encouraging for those with follicular small cleaved and mixed histologies.

Clinical features and results of management of superior vena cava syndrome secondary to lymphoma.

Thirty-six of 915 patients with non-Hodgkin's lymphoma presented with superior vena cava syndrome (SVCS). The histologic types associated with SVCS were diffuse large cell in 23 patients, lymphoblastic in 12, and follicular large cell in one patient. Radiotherapy alone appeared equal to chemotherapy alone or in combination with radiotherapy in achieving relief of SVCS symptoms. Chemotherapy alone or in combination with radiotherapy was superior to radiotherapy alone in prolonging relapse-free survival and overall survival. No differences in relapse-free survival and survival were found between the patients treated with chemotherapy alone and those treated with chemotherapy and radiotherapy, but the addition of radiotherapy appeared to prevent local relapses in the group with large-cell lymphoma. The presence of symptoms of involvement of other mediastinal structures such as dysphagia, hoarseness, or stridor (DHS), a higher grade of intensity, and a shorter duration of symptoms (less than or equal to 2 weeks) appeared to adversely influence relapse-free survival and survival. The following conclusions were made: (1) a histologic diagnosis before the onset of treatment is desirable and feasible in patients presenting with SVCS except in those with severe respiratory distress, (2) both chemotherapy and radiotherapy are equally effective in alleviating the symptoms of SVCS, and (3) combined modality treatment with chemotherapy and radiotherapy results in a lower frequency of local relapses compared to chemotherapy alone but survival was similar in both groups.

Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.

Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease.

PURPOSE: Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD). PATIENTS AND METHODS: Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy. RESULTS: Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels. CONCLUSION: NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.

Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy.

The sperm production of 25 patients with Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was studied retrospectively. All but two patients also received radiotherapy treatment to pelvic and/or non-pelvic fields. Sperm counts were obtained from patients treated either with three or fewer (MOPP-2 group) or with five or more (MOPP-6 group) chemotherapy cycles. Recovery of spermatogenesis following treatment-induced azoospermia was significantly higher among the MOPP-2 patients (Mann-Whitney rank sum test, p = 0.001). Patients in this group who did not receive pelvic irradiation appeared to have greater recovery rates (p = 0.06). The results suggest that three cycles of MOPP chemotherapy represent a maximum exposure compatible with the recovery of spermatogenesis.

Calcium status following neck radiation therapy in Hodgkin's disease.

Substantial evidence links the development of primary hyperparathyroidism with a medical history of neck radiation therapy for benign disease. This report concerns 220 patients with Hodgkin's disease seen at The University of Texas M. D. Anderson Hospital, Houston, treated with neck irradiation. Serum calcium levels had been analyzed two to 22 years after radiotherapy. Hyperparathyroidism was confirmed at surgery in one patient with hypercalcemia 15 years after radiotherapy. However, the maximum follow-up was 22 years and in a reported series the mean interval between irradiation and the development of hyperparathyroidism has ranged from 29 to 47 years. We conclude that patients who have received neck radiation therapy for malignant disease are not at an increased risk for the development of hyperparathyroidism in the first two decades following treatment but should continue to be screened for this development in subsequent decades.

Thyroid lymphomas stages IE and IIE: comparative results for radiotherapy only, combination chemotherapy only, and multimodality treatment.

This study was undertaken to ascertain the influence of both more precise staging and more intensive treatment on results in 38 patients with Stage IE and IIE lymphomas of the thyroid. These patients were admitted between 1947 and 1984. Using the modified Rappaport system, the disease was classified as diffuse large cell in 32 patients. The initial investigation included lymphangiography in 25 patients, five of which had a staging laparotomy. The assigned stages were IEA--11, IEB--1, and IIEA--26. Treatment consisted of definitive radiotherapy alone in 15; combination chemotherapy and radiotherapy in 14; and chemotherapy alone in 6 patients. The remaining three patients were treated with surgery alone. In general, combination chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, and prednisone, with or without bleomycin (CHOP +/- Bleo). The overall 5-year survival and disease-free survival were 72 and 64%, respectively. For patients treated with radiotherapy only, results depended on stage. For Stage IE, the survival and disease-free survival were 100 and 83%, respectively. The corresponding Stage IIE results were 88 and 75%. Within this group, results were better for a subset of patients where disease did not involve the mediastinum. Survival and disease-free survival for combined modality treatment were both 77% (10 of these 17 patients had Stage IIE disease). Survival and disease-free survival for combination chemotherapy were 53 and 30% (all had Stage IIE disease). In conclusion, radiotherapy alone is excellent treatment for disease limited to the thyroid with or without cervical adenopathy. Results for patients with mediastinal extensions was unsatisfactory and the addition of combination chemotherapy is indicated.

Spinal cord dose reduction using an anterior 13 MeV electron field situated between a split anterior 60Co supraclavicular field.

As part of the treatment for lymphoma, disease involving the supraclavicular region has been treated with megavoltage 60Co photons to a midline dose of 30 to 45 Gy through an anterior involved field and a supplementary posterior field when necessary. The spinal cord was shielded with a 5 cm lead block during treatment to the posterior field. A typical 40 Gy treatment results in a dose to the lower cervical and upper thoracic spinal cord in the range of 22 to 26 Gy, a level that could compromise subsequent mediastinal treatment in the event of a relapse. To reduce this cord dose, the midportion of the anterior supraclavicular 60Co To reduce this cord dose, the midportion of the anterior supraclavicular 60Co field was replaced with a high-energy (13 MeV) electron port, which reduces the dose to the cord to below 6 Gy in the average adult patient. This modification of the routine supraclavicular treatment allows greater flexibility in future treatment in the event of a mediastinal relapse.

The adjuvant role of two cycles of MOPP and low-dose lung irradiation in stage IA through IIB Hodgkin's disease: preliminary results.

Fifty-eight laparotomy-staged I and II patients with upper torso presentations of Hodgkin's disease and 8 patients with lymphangiogram-staged lower torso disease were treated with radiotherapy alone or with 2 cycles of MOPP and radiotherapy. Patients with upper torso disease with either no mediastinal or only small mediastinal disease without hilar involvement and with no "B" symptoms were treated with mantle radiotherapy alone. Patients with large mediastinal masses or hilar disease were treated with 2 cycles of MOPP followed by definitive mantle irradiation and low dose lung irradiation. Those for whom "B" symptoms were the only adverse prognostic feature received 2 cycles of MOPP and mantle radiotherapy. Patients with lower torso disease were treated with radiotherapy alone if the disease was limited to the pelvis. Those with more extensive disease received 2 cycles of MOPP prior to radiotherapy. The 4-year survival for all 66 patients was 97%. The corresponding disease-free and freedom from second relapse figures were 77% and 92%. Survival for the patients with unfavorable presentations who received 2 cycles of MOPP and radiotherapy was 100%. It was 92% for the group with favorable presentations who were treated with radiotherapy only.

Long-term results with radiotherapy for Stage I-II follicular lymphomas.

PURPOSE: To analyze the long-term results with radiotherapy (RT) for early-stage, low-grade follicular lymphomas. METHODS AND MATERIALS: From 1960 to 1988, 80 patients with Stage I (n = 33) or II (n = 47), World Health Organization Grade 1 (n = 50) or 2 (n = 30) follicular lymphoma were treated with RT. The lymph nodes or spleen were involved in 97% of cases. The maximal tumor sizes ranged from 0.5 to 11.0 cm (median 2.0). The RT fields encompassed only the involved Ann Arbor nodal region (involved-field RT) in 9% of the patients. The fields also included 1-3 adjacent, grossly uninvolved nodal regions (regional RT) in 54% of patients but were smaller than mantle or whole abdominopelvic fields. Mantle or whole abdominopelvic fields encompassing up to 6 grossly uninvolved regions (extended-field RT) were used in the remaining 37% of patients. The total RT doses ranged from 26.2 to 50.0 Gy given in daily 1.0-3.0-Gy fractions. RESULTS: The follow-up of the surviving patients ranged from 3.5 to 28.7 years (median 19.0). No recurrences were found >17.0 years after RT, with 13 patients free of disease at their last follow-up visit 17.6-25.0 years after treatment. In 58% of cases, death was not from follicular lymphoma. The 15-year local control rate was 100% for 44 lymphomas <3.0 cm treated with only 27.8-30.8 Gy (median 30.0 in 20 fractions). Progression-free survival was affected by the maximal tumor size at the start of RT (15-year rate 49% vs. 29% for lymphomas <3.0 cm vs. > or =3.0 cm, respectively, p = 0.04) and Ann Arbor stage (15-year rate 66% vs. 26% for Stages I and II, respectively, p = 0.006). Ann Arbor stage also affected the cause-specific survival (15-year rate 87% vs. 54% for Stages I and II, respectively, p = 0.01). No significant difference was found in overall survival between those treated with extended-field RT and those treated with involved-field RT or regional RT (15-year rate 49% and 40%, respectively, p = 0.51). The 15-year incidence rate of Grade 3 or greater late complications according to the Subjective, Objective, Management, and Analytical scale in patients treated with 26.2-30.8 Gy vs. 30.9-50.0 Gy was 0% and 6%, respectively. CONCLUSIONS: RT can cure approximately one half of Stage I and one quarter of Stage II, World Health Organization Grade 1 or 2 follicular lymphomas. Follicular lymphomas <3.0 cm can be controlled locally with doses of 27.8-30.8 Gy, and there is a trend toward a higher incidence of late complications with doses of >30.8 Gy. Doses of 25-30 Gy delivered in 15-20 fractions should be examined prospectively in patients with follicular lymphomas of <3.0 cm.

Recovery of sperm production following radiation therapy for Hodgkin's disease after induction chemotherapy with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP).

PURPOSE: The effect on human male fertility of radiotherapy following chemotherapy for the treatment of Hodgkin's disease (HD) is unknown. The impact of radiation therapy, given after mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) chemotherapy, on sperm production is the focus of this study. PATIENTS: Serial semen analyses were performed on 34 patients with HD Stages I-III before NOVP chemotherapy, after chemotherapy prior to radiation, and after radiation therapy. The most inferior radiation portals for patients were: mantle, 1 patient; paraaortic-spleen, 3 patients; upper abdomen, 24 patients; abdominal spade, 4 patients; and pelvic, 2 patients. Testicular radiation dose measurements were available for 20 of these patients. RESULTS: Before the start of radiation, 90% of patients were normospermic. The magnitude of the decline in sperm counts was related to the measured testicular dose and/or radiation fields employed. The minimum postradiotherapy counts, expressed as a fraction of pretreatment counts, for the various treatment groups are as follows: paraaortic-spleen, 20%; upper abdomen, testicular dose < 30 cGy, 4%; upper abdomen, testicular dose 30-39 cGy, 0.9%; abdominal spade, 0.02%; and pelvis, 0%. The time to nadir of sperm counts averaged 4.5 months. Recovery to normospermic levels occurred in 96% of patients, with most recovering to that level within 18 months. CONCLUSION: The effect of radiation following NOVP chemotherapy on sperm counts was no greater than would be expected with radiation therapy alone. In most patients, sperm counts recovered to levels compatible with normal fertility.

Long-term outcome of treatment for Ann Arbor Stage I Hodgkin's disease: prognostic factors for survival and freedom from progression.

PURPOSE: The earliest stages of Hodgkin's disease are associated with excellent short-term survival with radiation therapy. This has led to controversies regarding pretreatment evaluation, the extent of irradiation, the role of chemotherapy, and the relative importance of prognostic factors. Long-term results were sought to address these controversies. METHODS AND MATERIALS: A retrospective study was conducted of patients with Stage I Hodgkin's disease treated at the M. D. Anderson Cancer Center from 1967 through 1987. The median age at presentation of 145 patients was 31 years, and the male-to-female ratio was 1.8. Pretreatment evaluation included lymphangiography and bone marrow aspiration and biopsy in all patients. Laparotomy was performed in 101 of the 145 patients (70%). There were 133 patients with supradiaphragmatic presentations; 12 patients had infradiaphragmatic adenopathy. Only five patients had B symptoms (3.5%). Histologic subtypes of the disease included lymphocyte predominance 17.9%, nodular sclerosis 40.7%, mixed cellularity 40.7%, and one unclassified Hodgkin's disease with primary splenic involvement. All patients were treated with radiotherapy, and 16 (11%) also received combination chemotherapy as part of their initial treatment. Radiotherapy techniques included involved/regional field in 49%, extended field in 42.7% (mantle or inverted Y), and subtotal nodal irradiation in 8.3%. Follow-up extended from a minimum of 30-339 months, with a median period of observation of 16.5 years. RESULTS: The median survival was 13.7 years. The 10- and 20-year survival rates were 83% and 66%, respectively. The only factor important for decreased survival was age >40 years at diagnosis (p < 0.0001). Out of 43 deaths, 11 were the result of Hodgkin's disease and the remaining 32 resulted from intercurrent disease, including treatment-related causes. Median freedom from progression was 10.5 years, and the 10- and 20-year freedom from progression were 76% and 69%, respectively. Out of 39 relapses, 5 (13%) occurred beyond 10 years. Women had higher freedom from progression (p = 0.0534) than men. Age, histology, bulk of disease, site of involvement including the mediastinal presentations, and the addition of chemotherapy did not influence the freedom of progression. Although very few patients (12 of 145) received subtotal nodal irradiation, the freedom from progression at 10 years was 91.7% for this group versus 64.7% for the group of patients who were treated with more limited techniques. CONCLUSION: Treatment with radiation therapy for patients with Stage I Hodgkin's disease leads to an excellent outcome, but patients require long-term surveillance as late relapses are not rare. Age is the only factor that affects survival, and gender marginally affects freedom from progression. Subtotal nodal irradiation may improve freedom from progression; further investigation of this treatment is justified.

Subdiaphragmatic stage I & II Hodgkin's disease: long-term follow-up and prognostic factors.

PURPOSE: To report long-term follow-up results and to analyze prognostic factors for overall and disease-free survival in patients with subdiaphragmatic Stage I & II Hodgkin's disease. METHODS AND MATERIALS: From September 1962 to April 1995, 109 patients presented at the M. D. Anderson Cancer Center with subdiaphragmatic Hodgkin's disease. The medical records of these patients were retrospectively reviewed; 22 patients who received no treatment at the M. D. Anderson Cancer Center or who had radiation therapy at other institutions were excluded. The remaining 87 patients formed the basis of this study. The median age of our group was 33 years with a male: female ratio of 3.3:1. The histological subtypes were nodular sclerosis in 21 (24.1%) patients, mixed cellularity in 31 (35.6%), lymphocyte predominance in 33 (37.9%), lymphocyte depletion in 1 (1.1%) and unclassified histology in 1 (1.1%). Of the patients, 32 (36.8%) underwent laparotomy for diagnosis or staging purpose, 74 (85.1%) had lymphangiography, and 35 (40.2%) had computerized tomography of the abdomen and pelvis. Among the patients, 22 (25%) had more than three sites of nodal involvement at presentation, 56 (64.4%) had pelvic or abdominal disease, and 14 (18.4%) had bulky disease that was defined as disease with the largest dimension > or = 7 cm. Stage distribution was IA in 33.3%, IIA in 39.1%, and IIB in 27.6%. Treatment was radiotherapy alone in 60 (69%) patients, chemotherapy and radiation in 23 (26.4%), and chemotherapy alone in 4 (4.6%). RESULTS: The 10- and 20-year actuarial overall survival rates for all patients were 74.6% and 55.3%, and the corresponding disease-free survival rates were 72.4% and 67.5%, respectively. On univariate analysis, age > 40 years, B symptoms, nodular sclerosis or mixed cellularity histology, and decreased albumin or hemoglobin levels were statistically significant adverse pretreatment factors for overall survival. B symptoms, decreased albumin level, more than 3 sites of disease at presentation, and Stage II were statistically significant negative pretreatment prognostic factors for disease-free survival. Only B symptoms and decreased albumin level predicted worse outcome in both overall and disease-free survivals. On multivariate analysis, age > 40 years, nodular sclerosis and mixed cellularity histology, and decreased hemoglobin levels were three independent risk factors for overall survival. An analysis of the pattern of failure revealed that the majority of the patients with central Stage II disease who did not receive mantle radiation failed in the supradiaphragmatic area. Late complications of radiation were infrequent. CONCLUSIONS: Long-term follow-up of this group of patients revealed similar overall and disease-free long-term survival, as would be expected from supradiaphragmatic Hodgkin's disease. For patients with central Stage II disease, it is anticipated that supradiaphragmatic radiation therapy would improve the disease-free survival.