Hodgkin's disease stages IA and IIA. A long-term follow-up study on the gains achieved by modern therapy

One hundred forty-nine supradiaphragmatic Stage IA and IIA Hodgkin's disease (HD) patients treated according to one of two different policies, were analyzed to quantitate the therapeutic gains achieved in recent years. Forty-nine patients were managed according to the pre-1969 policy consisting of mantle radiotherapy (XRT) only without laparotomy staging and without subdiaphragmatic treatment. These cases constitute the old series (OS). Ninety-eight patients after 1969 received staging laparotomy-splenectomy and were treated with total or subtotal nodal irradiation, and in a small number also multiagent chemotherapy (MAC). These patients constitute the new series (NS). All prelaparotomy IA and IIA cases are included in the NS even if they became Stage III at laparotomy. Salvage therapy for relapsing disease differed between the OS and NS. The majority of OS relapsing patients received salvage XRT, while the majority of relapsing NS patients received MAC. The NS and OS patient groups are comparable by pretreatment parameters. There is a large and statistically significant improvement in disease-free survival (DFS) and survival (S) in the NS over the OS. At 13 years the NS group had a DFS of 65% compared to 38% in the OS, and S in the NS was 82% compared to 37% in the OS. The improvement in DFS is almost totally due to the addition of prophylactic periaortic XRT in the NS patients. A striking reversal of relapse patterns for the OS and NS was observed. Periaortic nodal relapse occurred in 37% of the OS patients and accounted for 64% of all relapses, while in the NS this failure pattern occurred in only 2% of all cases. Supradiaphragmatic relapse accounted for 74% of all relapses in the NS. Improved salvage of relapsed patients in the NS further added to the overall gain in survival. Whereas no relapsed patient in the OS achieved long-term survival (14% at 10 years, 0 at 25 years), one-half of NS relapses were salvaged by MAC (54% survival at 10 years from relapse). These data clearly document the striking therapeutic gains in Stage IA and IIA supradiaphragmatic HD resulting from the use of prophylactic periaortic XRT and MAC salvage for relapsing patients.     

Results of treatment of stage IA and IIA Hodgkin's disease

This study analyzed the 5 year actuarial survival and disease-free survival of 122 patients with Stage IA and IIA Hodgkin's disease, (108 patients laparotomy staged) treated with mantle and paraaortic irradiation from 1975 to 1981. Prognostic subgroups and patterns of treatment failure were investigated. The 5 year actuarial survival and disease-free survival was 91% and 75% respectively for the entire group. For Stage IA patients, the 5 year survival and disease-free survival was 92% and 86% respectively, whereas for those in Stage IIA the respective figures were 86% and 65%. Individuals with greater than four sites of involvement at initial presentation; extensive mediastinal adenopathy; hilar or extramediastinal extension to lung, pleura or pericardium, had a poorer 5 year actuarial disease-free survival (43%-60%) than those without these factors (70%-85%). Of the 122 patients, there were 26 relapses: nine infield failures; two concurrent infield and systemic failures; nine marginal recurrences, and three relapses occurring systemically and three in nodal groups not irradiated. Following relapse, 17 patients were salvaged with chemotherapy. Two patients are alive with disease and seven patients died of Hodgkin's disease. Patients with less extensive mediastinal adenopathy and supradiaphragmatic nonmediastinal presentations can be satisfactorily treated with mantle and paraaortic irradiation, whereas patients with extensive mediastinal adenopathy receive six cycles of multiagent chemotherapy before irradiation.     

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone.

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.     

Outcome analysis of localized gastrointestinal lymphoma treated with surgery and postoperative irradiation

One hundred thirteen patients with localized gastrointestinal lymphoma treated by surgery and postoperative irradiation between 1967 and 1985 were reviewed. At 15 years, actuarial survival of this group was 40.6%, with a cause-specific survival of 69.2% and a relapse-free rate of 64%. Two-thirds of relapses occurred at distant sites. In Stage IA and IIA patients with no residuum or with positive resection margins, (N = 90) only site of involvement and stage predicted for relapse. Age, histologic subtype group, and depth of bowel wall invasion did not affect relapse risk. In the very favorable group (Stage IA, IIA, no residuum or microscopic residuum), 8.4% of patients with stomach lymphoma relapsed compared to 25% of patients with small bowel lymphoma. The risk of early relapse was higher in those with Stage IIA small bowel lymphoma than those with Stage IA small bowel lymphoma. We continue to recommend adjuvant abdominal irradiation for patients with Stage IA, IIA completely resected stomach lymphoma and Stage IA completely resected small bowel lymphoma. We recommend combined modality therapy for patients with completely resected Stage IIA small bowel lymphoma and all other localized gastrointestinal lymphoma where visible residual disease is present.     

Radiotherapy for stage 2 testicular seminoma: the prognostic influence of tumor bulk

Forty-nine consecutive patients with stage 2 testicular seminoma were treated with primary radiotherapy from 1968 to 1985. Overall diseases-free survival (DFS) for patients with 36 months minimum follow-up was 82% at 3 years. This figure did not decline further with time. Infradiaphragmatic bulk disease was found to be a significant prognostic factor for local and distant relapse as well as for ultimate survival. Patients with either stage 2A or 2B disease (infradiaphragmatic bulk less than or equal to 10 cm size) had a 3-year DFS of 89% compared with a 64% 3-year DFS rate for patients with stage 2C disease (infradiaphragmatic bulk greater than or equal to 10 cm size). The (local plus distant) relapse rate was 4.0% for patients with stage 2A disease, 16.7% for patients with stage 2B disease, and 33.3% for patients with stage 2C disease. The majority of distant relapses were multifocal and prophylactic mediastinal irradiation did not appear to influence either relapse rate nor overall survival. Of seven patients who relapsed, four died of progressive malignancy, two deaths were related to salvage chemotherapy, and only one patient is alive and well following successful chemotherapeutic salvage. On the basis of our experience, we recommend radiotherapy with the use of modern imaging techniques as initial treatment for patients with retroperitoneal masses less than 10 cm size. Aggressive cisplatin-based chemotherapy should be seriously considered for patients with retroperitoneal masses greater than or equal to 10 cm size, or for patients who relapse following radiotherapy.     

Prognostic significance of mediastinal mass in adult Hodgkin's disease

The authors analyzed the prognostic significance of mediastinal involvement with Hodgkin's disease in 169 pathologically stage adults (greater than or equal to 17 years) treated at the Mayo Clinic between 1974 and 1978. Sixty percent of the patients presented with mediastinal disease, evenly divided between those with a mediastinal to thoracic ratio (MTR) less than 0.33 and greater than or equal to 0.33. They were of younger average age and were more likely to have nodular sclerosis histologic subtype than those patients without a mediastinal mass. The median follow-up from diagnosis was 4.1 years with 90% of the patients being followed for 2 or more years. The 5-year disease-free survival (DFS) for the radiation only group was 70% in patients without mediastinal disease, 53% in the less than 0.33 MTR group and 44% in the greater than or equal 0.33 MTR group (P = 0.25). The 5-year survival was 92% in the patients without mediastinal disease, 88% in the less than 0.33 MTR group and 90% in the greater than or equal to 0.33 MTR group (P = 0.70). This lack of significant difference both in the 5-year DFS and survival between the three groups was also seen in the patients taken in toto (169) and in those receiving combined modality treatment (36). However, in early stage (I and II) patients, treated with radiation only, those with a large mediastinal mass had a 5-year DFS (33%) that was significantly worse than both the small mass patients (71%) and those with no mediastinal mass (87%) P less than 0.005). The pattern of relapse in the 40 patients who failed following treatment by radiation only was not affected by an increasing size of mediastinal involvement. At the time of this analysis 27 of the 40 patients who had relapsed following treatment by radiation only (all stages) had remained free from second relapse. The authors do not believe that the current data either support or negate the use of a combined modality approach in the initial treatment of Hodgkin's disease patients presenting with a large mediastinal mass. Only further follow-up will establish whether the treatment of patients, who have relapsed following radiation only, is durable and results in an overall survival comparable to that obtained by using combined modality initially.     

Prognostic value of the 2002 TNM classification for breast carcinoma with regard to the number of metastatic axillary lymph nodes

BACKGROUND: The American Joint Committee on Cancer (AJCC) TNM classification for breast carcinoma had not been changed for 15 years, since the publication of the third edition in 1987. However, in the sixth edition, published in 2002, significant modifications were made with regard to the number of metastatic axillary lymph nodes. The authors investigated whether the sixth edition of the TNM classification provided more reliable prognostic information compared with the third edition. METHODS: The records of 1230 patients who underwent surgery for invasive breast carcinoma between 1993 and 1999 were reviewed. Each patient was assigned to axillary lymph node and disease stage groups according to the 1987 and 2002 AJCC TNM classifications. Disease-free survival (DFS) curves were calculated and plotted using the Kaplan-Meier method and the two-sided log-rank test was used to compare the survival curves of the patient groups. RESULTS: Of the 1067 patients who were classified as having Stages II and III disease according to the 1987 classification, 411 (38.5%) were shifted to higher disease stages using the 2002 classification. Among the 1987 Stage IIA, Stage IIB, and Stage IIIA patients, the DFS rates of the patients who were shifted to higher stages of disease were significantly worse than those of the patients for whom the stage of disease was not changed. Among those patients classified as having T4anyNM0 (Stage IIIB) disease according to the 1987 classification, there was no survival difference noted between those patients with T4N0,1,2M0 disease (who formed the Stage IIIB group) and those with T4N3M0 disease (who formed the Stage IIIC group) according to the new staging system. Of the 221 patients who formed the new Stage IIIC group, 12.2% were classified as having Stage IIA disease, 42.1% as having Stage IIB disease, 38.9% as having Stage IIIA disease, and 6.8% as having Stage IIIB disease according to the 1987 classification. The survival rates of these Stage IIA, Stage IIB, and Stage IIIA patients were not found to be significantly different; however, the survival of patients in the Stage IIIB group was found to be significantly worse than the survival of the patients in the other disease stage groupings, and the patients in the Stage IIIC group were not a prognostically homogeneous group. On the basis of these results, the authors placed patients with T4anyNM0 disease in the same group (Stage IIIB). When the 2002 classification was rearranged in this manner, patients with Stage IIIC disease formed a homogeneous group; the 5-year DFS rate of patients with Stage IIIB disease was found to be significantly worse than that for patients with Stage IIIC disease (P = 0.0011). CONCLUSIONS: In the 2002 TNM classification for breast carcinoma, patients with T4anyNM0 disease should form a distinct stage grouping and this stage grouping (Stage IIIC) should be placed before Stage IV, and Stage IIIB disease groupings should include patients with T1,2,3N3M0 disease. In this way, the authors hope that the 2002 AJCC TNM classification, which provides more reliable prognostic information than the 1987 classification, will become more refined.     

Prognostic factors for Stage IV Hodgkin's disease treated with MOPP, with or without bleomycin

Prognostic factors for 53 previously untreated patients with Stage IV Hodgkin's disease were analyzed for their effects upon complete remission rate, survival, and disease-free survival following treatment with mechlorethamine, Oncovin (vincristine), procarbazine, and prednisone (MOPP) or MOPP plus bleomycin (MOPP-Bleo). Although 75% of those patients with only one site of extranodal disease achieved complete remission, only 25% of those with more than one site of involvement entered complete remission. Seven of the eight patients with more than one extranodal site were dead of disease at 4 years, compared with a 5-year survival of 75% for those with only one site of involvement. Disease-free survival from complete remission was dependent upon the percentage of planned doses of nitrogen mustard actually administered. Patients who received higher doses of nitrogen mustard had significantly longer freedom from relapse and survival after attaining complete remission than those who received reduced doses. Age, symptoms, pathologic features, and presence or size of mediastinal disease did not affect the couple remission rate, survival, or disease-free survival. Patients with Stage IV disease treated with MOPP alone should receive the highest tolerable dose of nitrogen mustard early in their treatment, since those receiving lower doses have a higher risk of relapse.     

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.     

Stage IA and IIA supradiaphragmatic Hodgkin's disease: prognostic factors in surgically staged patients treated with mantle and paraaortic irradiation

A total of 315 pathologically staged (PS) patients with IA and IIA Hodgkin's disease (HD) were treated with mantle and paraaortic irradiation, and evaluated for freedom-from-first relapse (FFR), survival, prognostic factors, and long-term complications. The 14-year actuarial FFR and survival were 82% and 93%, respectively, with a median follow-up time of 9 years. Mediastinal size was the only factor that predicted for a lower FFR, P less than .001. Forty-nine patients have developed recurrent HD. Thirty-six patients are disease-free following retreatment and only 13 patients have died of HD. Patients with mixed cellularity (MC) histology were more likely to relapse below the diaphragm (11%) as compared with patients with nodular sclerosis (NS) (5.1%) or lymphocyte predominant (LP) (3.6%) histology. These relapses were often associated with bulky pelvic nodal adenopathy and salvage treatment with chemotherapy alone often failed to control recurrent disease. Alternative diagnostic and therapeutic recommendations are presented for these patients. Thyroid abnormalities represented the most common long-term complication with an actuarial risk at 16 years of 37%. Major complications were rare. Mantle and paraaortic irradiation is associated with a high FFR and a low risk of complications and should remain standard treatment for early-stage HD.     

Prognostic groups for management of localized Hodgkin's disease

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

Correlation between radiation dose and tumor recurrence and complications in carcinoma of the uterine cervix: stages I and IIA.

A retrospective analysis is reported on 330 patients with carcinoma of the uterine cervix, 23 with Stage IA, 233 with Stage IB and 74 with Stage IIA disease treated with irradiation alone. The dose of irradiation delivered to the cervix, paracervical tissues or the pelvic lymph nodes was correlated with tumor control. There were no central or parametrial failures in patients with Stage IA disease. There were 4 local or marginal (central) recurrences (1.6%) and 15 (6.5%) parametrial failures in the patients with Stage IB disease. Of 74 patients with Stage IIA disease, 3 developed cervical failures (3.9%) and 4 had both central and parametrial recurrences (5.2%).A definite correlation was found between the dose of irradiation delivered to the pelvic lymph nodes and the incidence of recurrences in the patients with Stage IB disease, (about 20%) parametrial failures with doses below 4000 rad in contrast to about 5% with 4000–5000 rad and 2% with doses over 6000 rad). Among patients with Stages IB and IIA disease, the survival of those who were treated with radiation alone and who received doses less than 4000 rad was about 10% less than patients who were treated with higher doses. This difference is not statistically significant; however, it suggests strongly that higher doses of irradiation to the parametria correlate with better tumor control in the pelvis and survival. Complications were slightly higher with doses to the bladder or rectum over 8000 rad. Although it was not statistically significant, patients who had non-standard intracavitary insertions had approximately 18% complications in contrast to only 6.6% in 135 patients with adequate insertions. Factors other than total dose of irradiation, such as geometry of the pelvis, characteristics of the tumor, position of the applicator, type of applicators used, loading and dose rate are important in evaluating the effects of irradiation in tumor control and complications of carcinoma of the uterine cervix.     

Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone.

The authors conducted a retrospective analysis of 1178 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. The minimum follow-up time was 3 years. The 10-year actuarial pelvic failure rate in Stage IB was 6% for tumors less than 3 cm, 15% for tumors 3 to 5 cm, and 30% for tumors more than 5 cm (P = 0.0018). The 10-year actuarial pelvic failure rate in Stage IIA was 10% for tumors less than 3 cm, 28% for tumors 3 to 5 cm, and 20% for tumors more than 5 cm (P = 0.09). Stage IIB unilateral nonbulky tumors (less than 5 cm) had a 20% pelvic failure rate compared with 28% for bilateral lesions and 35% for unilateral bulky tumors (more than 5 cm) (P = 0.35). In Stage IIB, pelvic failures were greater when disease extended into the lateral parametrium (30%) compared with medial parametrial involvement only (17%) (P = 0.01). In Stage III unilateral nonbulky tumors, the pelvic failure rate was 28% compared with 45% to 50% for unilateral bulky lesions (P = 0.002). Bilateral parametrial disease in Stage IIB did not increase the pelvic failure rate (21% in both subgroups) (P = 0.83), whereas in Stage III, bilateral parametrial involvement was associated with a 48% pelvic failure rate versus 28% for unilateral extension (P less than or equal to 0.01). Five-year disease-free survival (DFS) rates for IB tumors less than or equal to 3 cm was 90% versus 67% for tumors more than 3 cm (P = 0.01). In Stage IIA tumors less than or equal to 3 cm, 5-year DFS was 70% versus 45% for tumors more than 3 cm. Patients with Stage IIB nonbulky tumors (less than or equal to 5 cm in diameter) had better 10-year DFS (65% to 70%) compared with those with bilateral bulky tumors (45% to 55%) (P = 0.10). Stage III patients with unilateral nonbulky tumors had a 55% 10-year DFS compared with 35% to 40% for bulky tumors or bilateral parametrial involvement (P = 0.002). The authors concluded that clinical stage and size of tumor are critical factors in the prognosis, therapy selection, and evaluation of results in carcinoma of the uterine cervix.     

Are pelvic irradiation and routine staging laparotomy necessary in clinically staged IA and IIA Hodgkin's disease?

Thirty-nine patients with clinically staged IA and IIA Hodgkin's disease were treated with mantle plus paraaortic/splenic irradiation between 1968 and 1975. All patients had supradiaphragmatic presentations, and none had staging laparotomies. With a follow-up time of 1 to 9 years, mean 4.3 years, the overall relapse-free survival is 92% (100% for stage IA and 89% for stage IIA). The absolute relapse-free 5-year survival is 91% There were no pelvic recurrences. These data show that routine staging laparotomy and pelvic irradiation are not indicated for clinically staged IA and IIA Hodgkin's disease with supradiaphragmatic presentation. The criteria for staging laparotomy in early-stage Hodgkin's disease are discussed.     

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.     

A randomized study of two doses of abdominopelvic radiation therapy for patients with optimally debulked stage I,II, and III ovarian cancer

Purpose: To determine whether an increased dose of abdominal radiation therapy results in improved disease control and survival in patients with early ovarian cancer.Methods and Patients: Between 1981 and 1990, 125 patients with optimally debulked Stage I, II, and III ovarian cancer were entered into a prospective randomized clinical trial of abdominopelvic radiation therapy. Patients were stratified and randomized to either the control arm, treated with an abdominal dose of 22.5 Gy in 22 fractions, or the experimental arm of 27.5 Gy in 27 fractions. A pelvic boost dose of 22.5 Gy was used in both arms. There were 43 patients with Stage I tumors, 71 Stage II tumors, and 11 Stage III tumors. Nineteen patients had grade 1 histology, 77 grade 2, and 29 grade 3. Three patients had small-volume residual disease (<2 cm) in the pelvis alone and the remainder had no gross tumor following surgery. Median follow-up was 6.6 years (range 1.4–9.9).Results: Overall survival (OS) at 5 years was 83% in the low-dose arm and 72% in the high-dose arm (p = 0.3). Disease-free survival (DFS) at 5 years was 74% and 67% in the low-dose and high-dose arms, respectively (p = 0.5). The difference in OS between the two arms was −11%, with 95% confidence intervals of −26% (favoring low-dose treatment) to 4% (in favor of high dose). The difference in DFS was −7% (95% confidence interval, −23 to 9%). Failure in the pelvis alone predominated (n = 15); six patients had abdominal and pelvic failure and seven patients failed in the abdomen alone. There were no differences in patterns of relapse, hematologic toxicity, or late complications between the two arms. Serious bowel toxicity was seen in three patients: two in the low-dose and one in the high-dose arm. A Cox proportional hazards model was used to assess the effect of treatment when adjusting for other prognostic variables. Ascites (p = 0.03, relative risk 2.05) was the only significant covariate in predicting disease-free survival, but was not prognostic for overall survival.Conclusions: There was no difference in survival, tumor control, or toxicity between high-dose and low-dose abdominopelvic radiation therapy. High-dose abdominopelvic radiation therapy is unlikely to be associated with an increase in OS of more than 4% or DFS of more than 9%.     

Stage I-II follicular lymphoma. Treatment results for 76 patients

Clinical features and treatment results are analyzed for 76 patients with Stage I-II follicular lymphoma seen between 1974 and 1981. During this period, 66% of the patients received involved-field radiotherapy (XRT) alone, and 34% received chemotherapy with or without XRT. At 5 years, the overall survival was 67%, the cause-specific survival was 73%, and the relapse-free survival (RFS) was 48%, with no relapses to date among nine patients followed beyond 60 months. Adverse prognostic features for survival included extranodal disease and elevated serum lactate dehydrogenase. For RFS, adverse features included extranodal disease and bulky abdominal disease. The RFS was significantly better for patients receiving chemotherapy with or without XRT than for XRT alone (64% versus 37% at 5 years, P = 0.02), despite a higher frequency of adverse prognostic features in the chemotherapy-treated group. About 50% of Stage I-II follicular lymphoma patients may be curable, and the inclusion of chemotherapy in the initial treatment may increase the potentially curable fraction.     

Hodgkin's disease: a reassessment of prognostic factors following modification of radiotherapy

Between 1970 and 1982, 175 patients with Stage IA, B, IIA, B, or IIIA Hodgkin's disease were treated with curative radiotherapy following surgical staging. The patients treated prior to 1975 received either regular extended or total nodal field treatments (Treatment Group 1, N = 65). Unsatisfactory results from this treatment program led to treatment modification in 1975. The modified protocols consisted of low-dose lung irradiation in patients having large mediastinal masses and/or hilar disease, and low-dose liver irradiation for Stage IIIAS+ patients (Treatment Group 2, N = 110). Recurrence-free survival rates improved significantly for various risk groups. Univariate analysis indicated that age, stage, symptoms, mediastinal mass size, number of sites involved, hilar disease, stage, and symptoms were significant risk factors in Treatment Group 1. In Treatment Group 2, only sex was a statistically significant risk factor. Stepwise Cox regression analysis for risk factors selected mediastinal mass size and stage as the most significant prognostic factors in Treatment Group 1. In Treatment Group 2, number of initial disease sites and sex were the most significant risk factors. The results of the study show significant improvement in recurrence-free survival rates in Treatment Group 2. It is concluded that these improvements are due to the modification in treatment.     

Medically inoperable stage I endometrial carcinoma: a few dilemmas in radiotherapeutic management

PURPOSE: The aggressiveness of radiation therapy for patients with medically inoperable endometrial carcinoma is controversial. Patients may die of their underlining medical disease before succumbing to cancer. We try to identify certain subgroup of patients who might benefit most from an aggressive approach and also investigate the impact of residual tumor present in dilatation and curettage (D&C) specimen obtained in second intracavitary implant (ICI). METHODS AND MATERIALS: From 1965 to 1990, 101 patients were treated for clinical clinical Stage I endometrial carcinoma with RT alone due to medical problems. Ages ranged from 39 to 94 years (median 71 years). There were 18 patients with clinical Stage IA and 83 with clinical Stage IB disease. Histology included 44 well-differentiated, 37 moderately differentiated, and 20 poorly differentiated tumors. Radiation therapy consisted of external beam only in 3 patients, ICI alone in 26, whole pelvis plus ICI in 10, and whole pelvis plus split field plus ICI in 62. A second D&C was performed on 26 patients at the time of the second ICI. Minimum follow-up was 2 years (median, 6.3 years). RESULTS: The 5-year actuarial disease-free survival (DFS) for the studied cohort is comparable to the expected survival of an age-matched population. Pelvic control was 100% for Stage IA and 88% for Stage IB with 5-year disease-free survivals of 80 and 84%, respectively. We also observed a greater disassociation of DFS and overall survial among patients older than 75 years (84 and 55%, respectively) than in younger patients (84 and 78%, respectively). This is mainly because older patients succumbed to their medical illness. Well-differentiated disease demonstrated the trend toward a better outcome than moderately or poorly differentiated lesions in Stage IB patients (p = 0.05), but not in Stage IA patients. Aggressive radiation therapy approach showed the trend toward a better result in Stage IB patients 75 years of age or younger. There were two failures among 19 patients with no tumor found in the D&C specimen at the time of second implant. In contrast, seven patients with residual tumor seen in the endometrial sample at the time of second implant remain disease free. CONCLUSIONS: Radiation therapy alone is an effective treatment modality for medically inoperable Stage I endometrial carcinoma. Disease-free survival can be translated into longer overall survival in the younger age group, but not in older patients. The latter tend to die of their underlining medical illness. Tumor differentiation influenced the prognosis of Stage IB disease. No tumor seen in the endometrial sampling at the time of second implant did not correlate with a better disease control, and the treatment plan should not be modified on such information.     

Subdiaphragmatic Hodgkin's disease: the University of Florida experience.

PURPOSE: To assess the long-term outcomes and late effects of patients with subdiaphragmatic Hodgkin's disease. METHODS AND MATERIALS: Twenty-one patients with Stage I and II subdiaphragmatic Hodgkin's disease were treated with curative intent between February 1966 and February 1998 at the University of Florida. Patient characteristics were as follows: mean age, 38.7 years (range, 3-75 years); 20 males and 1 female; 33% lymphocyte predominant, 43% nodular sclerosing, 14% mixed cellularity, 5% lymphocyte depletion, and 5% unclassified Hodgkin's disease. Treatment included inverted Y irradiation (InY) (8 patients), total nodal irradiation (TNI) (7 patients), and combined modality irradiation and chemotherapy (CMT) (6 patients). Median follow-up was 12.3 years (range, 3.1-33.6 years). RESULTS: Progression-free survival and overall survival were 80% and 70%, respectively, at 10 years. There were no deaths from Hodgkin's disease. Treatment failures occurred in 1 of 8 patients after InY, 1 of 7 after TNI, and 1 of 6 after CMT. Two of 3 recurrences were in patients with 3 or more sites of involvement and/or splenic involvement; 1 was in-field. There were 5 second malignant neoplasms and 3 cardiac events, including 4 second malignant neoplasms and 2 cardiac events in the 9 patients > or =40 years old at diagnosis and 1 second malignant neoplasm and 1 cardiac event in the 12 patients <40 years old. All 3 second solid malignancies in this study occurred 7-14 years after treatment in areas receiving 10-20 Gy. CONCLUSIONS: Subdiaphragmatic Hodgkin's disease is an uncommon manifestation with excellent disease control achieved with InY, TNI, and CMT. This subgroup of patients with Hodgkin's disease is predominantly male and older than subgroups with other presentations, which may predispose the group to a higher risk for serious adverse events after treatment. We recommend InY with spleen for clinical Stages IA and nodular sclerosis or lymphocyte-predominant clinical Stage IIA, InY alone for pathologic Stages IA and IIA, and CMT for all Stage I/II patients with greater than three involved sites, B symptoms, bulky disease (>6 cm), central (para-aortic) presentation, or splenic involvement.