Serafin Delgado

Primary breast lymphoma: results of a controlled clinical trial.

Objectives: To assess the efficacy and toxicity of the most employed therapeutic approaches in the treatment of primary breast lymphoma (PBL). Methods: Ninety-six patients with PBL in the early stage (I or II) were enrolled to receive radiotherapy (45 Gy); chemotherapy (six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), every 21 days), or combined therapy. Results: Complete response was achieved in 20 of 30 patients treated with radiotherapy, 19 of 32 who were treated with chemotherapy and 30 of 34 in the combined arm (p < 0.01). Actuarial curves at 10 years showed that event-free survival was 50, 57 and 83%, respectively (p < 0.01). Actuarial curves for overall survival were 50, 50 and 76% (p < 0.01), respectively. The most common site of relapse was the central nervous system. Acute toxicity was mild. Until now, no second neoplasm or acute leukemia has been observed. Conclusions: In our study combined therapy is the best treatment in this special setting of patients; with improvement in event-free survival and overall survival without acute or severe late side effects. Prophylaxis to the central nervous system will be considered in the initial treatment to improve outcome.

Adjuvant radiotherapy to sites of previous bulky disease in patients stage IV diffuse large cell lymphoma.

PURPOSE To evaluate the usefulness of adjuvant radiotherapy to sites of previous bulky disease in patients with advanced diffuse large cell lymphoma (DLCL) who were in complete remission after chemotherapy. METHODS AND MATERIAL Two-hundred and eighteen patients were initially treated with combined chemotherapy CEOP-bleo (cyclophosphamide, epirubicin, vincristine, prednisone, bleomycin) alternating with DAC (dexamethasone, cytosine arabinoside, and cisplatinum). One hundred and fifty-five patients achieved complete remission. Eighty-eight patients with initial bulky disease were randomly assigned to either received (43 patients) or not received radiotherapy (45 patients). Dose ranged from 40-50 Gy. RESULTS The median time to treatment failure has not been reached in patients who received radiotherapy. At 5 years 72% of the patients treated with the combined therapy remain alive disease in free compared to only 35% in the control group. Projected survival at 5 years was better in the patients with adjuvant radiotherapy: 81% compared to 55% in the patients who received no radiotherapy. Toxicity was mild and manageable. No lethal toxicities were observed. CONCLUSION This treatment sequence produced durable control disease in patients with disseminated DLCL and bulky disease with acceptable toxicity. The role of radiation therapy in patients with disseminated DLCL will be confirmed in large clinical trials, but we felt that this sequence of treatment could be useful in patients with this clinical condition.

IMPROVED OUTCOME IN SOLITARY BONE PLASMACYTOMATA WITH COMBINED THERAPY

Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease‐free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow‐up of 8·9 years, disease‐free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p<0·01). Treatment was well tolerated; planned doses were administered in all cases; no delays in treatment or acute side‐effects were observed during treatment. Long‐term secondary toxicities including secondary neoplasms and acute leukaemia, have not been observed. We felt that the use of adjuvant chemotherapy after adequate doses of radiotherapy in patients with SBP improved duration of remission and survival without severe side‐effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

Residual disease after chemotherapy in aggressive malignant lymphoma: the role of radiotherapy.

Residual disease in patients with diffuse large B-cell lymphoma after intensive chemotherapy remains a problem. Radiotherapy has been used in some retrospective studies without definitive conclusions. We report the first controlled clinical trial to define the role of radiotherapy in this setting of patients. One hundred and sixty-six patients with diagnosis of diffuse large B-cell lymphoma, high- or high-intermediate clinical risk, with residual disease (defined as tumor mass <5 cm) were randomly assigned to received radiotherapy at the involved field, with 30 Gy delivered in 20 sessions or no radiation (control group). Median follow-up was 135 mo; patients who received radiotherapy have an better outcome. Actuarial curves at 10 yr showed that progressive-free disease was 86% and overall survival was 89%; those were statistical significant when compared to patients who did no received radiotherapy: 32% and 58% respectively, (p<0.001). Toxicity was mild and well tolerated. We concluded that presence of residual mass after chemotherapy in patients with aggressive malignant lymphoma has a worse prognosis, and salvage radiotherapy improves outcome with mild toxicity. We feel that radiotherapy will be considered as necessary treatment in this special group of patients.

Patterns of recurrence following pelvic exenteration and external radiotherapy for locally advanced primary rectal adenocarcinoma

AbstractBackground: Local recurrence remains the main site of failure after pelvic exenteration for locally advanced primary rectal adenocarcinoma. This is a report on the patterns of recurrence in a group of such patients treated with pelvic exenteration and radiotherapy. Methods: Between 1980 and 1992, we treated 49 patients. Thirty-one received preoperative radiotherapy (pre-RT), 4,500 cGy. Six weeks later, we performed posterior pelvic exenteration (PPE) in 21 patients, and total pelvic exenteration (TPE) in 10. Nine patients received postoperative radiotherapy (post-RT), 5,000 cGy after a PPE. Nine patients had surgery only, PPE (n=7) and TPE (n=2). Results: Surgical mortality occurred in 16% of those patients who received pre-RT. The median follow-up was 52 months. Recurrences occurred in 23% of those patients who received pre-RT (local, one; local/distant, one; distant, four); in 88% of those patients treated with surgery only (local/distant, four; distant, four); and in 11% of those treated with post-RT (distant, one). The 5-year survival for patients who received radiotherapy was 66 versus 44% for those treated with surgery only. Conclusion: Local control of locally advanced primary rectal adenocarcinoma requiring a pelvic exenteration is improved by the addition of radiotherapy. When recurrences do occur they are predominantly at extrapelvic sites.

Inguinal lymph node metastases from rectal adenocarcinoma.

The prognosis of patients with inguinal lymph node metastases from rectal adenocarcinoma is poor. The purpose of this study is to analyze the clinical behavior and response to different therapies in a group of these patients.

Combined therapy in advanced stages (III and IV) of follicular lymphoma increases the possibility of cure: results of a large controlled clinical trial.

Abstract: Objectives: We evaluate the long‐term results of a randomized clinical trial in patients with advanced stages (III and IV) of follicular lymphoma using chemotherapy or combined therapy (chemotherapy following by adjuvant radiotherapy in patients with nodal bulky disease). Material and methods: Between 1981 and 1995, patients with follicular lymphoma were treated with combined chemotherapy, mostly anthracycline‐based regimens; patients who achieved complete response were randomly assigned either to receive adjuvant radiotherapy to sites or to nodal bulky disease or not (control group). Results: Four hundred and sixty‐nine patients were randomized; in an intent‐to‐treat analysis all were evaluable for efficacy and toxicity. Actuarial curves at 20 yr showed that event‐free survival (EFS) and overall survival (OS) in the control group were 41% [95% confidence interval (CI) 36–56%) and 71% (95% CI 65–78%), respectively; these were statistically different from results for the patients who received adjuvant radiotherapy: 68% (95% CI 62–72%) and 89% (95% CI 79–96%), respectively (P < 0.01). Acute and late toxicity were minimal; only four patients (< 1%) developed myelodysplastic syndrome/acute leukemia. Cardiac toxicity was 2%, but one case was lethal. Thirty‐six patients (8%) died secondary to unrelated causes, in complete remission. Conclusions: The use of adjuvant radiotherapy in patients with poor‐prognosis follicular lymphoma increases EFS and OS with minimal toxicity. We feel that follicular lymphoma should be treated curatively because < 80% of patients will be in first complete response at < 20 yr. The use of adjuvant radiotherapy will be considered in the first line of treatment in this set of patients.

Marginal zone B cell lymphoma of the parotid glands: results of a randomised trial comparing radiotherapy to combined therapy.

39 patients with marginal zone B cell lymphoma (MZBCL) of the parotid glands (stages I or II) were studied. They were randomized to be treated with either radiotherapy alone (extended fields, 4500 cGy) or radiotherapy (the same schedule) plus adjuvant chemotherapy (cyclophosphamide, vincristine and prednisone). The end points were survival and time to treatment failure (TTF). Patients who received radiotherapy alone had a complete remission rate of 100%, the TTF was 90% at 5 years and overall survival at 5 years was 90% with no statistical difference when compared with patients who received combined therapy [100, 80 and 95%, respectively (P = 0.5)]. Although adjuvant chemotherapy was well tolerated, the use of this therapeutic approach in patients with early stage MZBCL did not offer any advantage over radiotherapy alone as the initial treatment. Until now, radiotherapy was considered the treatment of choice in this clinical setting of patients.

Intensive brief chemotherapy with hematopoietic growth factors as hematological support and adjuvant radiotherapy improve the prognosis in aggressive malignant lymphoma.

An intensive brief chemotherapy and radiotherapy regimen including high doses of cyclophosphamide (5 g/m2), etoposide (1 g/m2), epirubicin (180 mg/m2), and ifosfamide (5 g/m2) administered in a period of 30 days followed by involved field radiotherapy to sites of initial bulky disease was administered to 46 untreated patients with high‐intermedium and high‐risk malignant lymphoma. G‐ or GM‐CSF were used as hematological support instead of bone marrow transplantation. All patients had more than 3 adverse prognostic factors at diagnosis.

Usefulness of frozen-section examination in resected mid-rectal cancer after preoperative radiation

The surgical treatment of rectal cancer of the middle third remains controversial. We treated 30 consecutive patients with preoperative radiotherapy (45 Gy) and low anterior resection. Anastomoses were performed with a stapler. Intraoperative frozen-section examination of the rectal margin established that it was free of tumor. Two patients died of surgery-related causes. Median follow-up of the remaining patients is now 52 months (range: 26 to 76 months). Eight patients had recurrences documented at surgical re-exploration: two local (pelvic) only, three local and distant, and two distant only. Local recurrences happened despite a frozen-section examination of the rectal margin negative for tumor. Six of the eight patients who experienced a recurrence have died of disease progression. Distant metastases were found in six other patients during follow-up; they subsequently died. Thus, our therapeutic approach was not associated with decreases in local or overall recurrences.