Orbital follicular lymphoma with large cell component treated with low-dose radiotherapy: A case report and review of literature.

A 77-year-old woman was referred for a one-eyed palpebral edema associated with diplopia. An orbit magnetic resonance imaging showed an orbital mass in the superior medial portion of the internal right orbit without any intraorbital involvement. Biopsies demonstrated a nodular lymphoma with mixed follicular grade 1-2 (60%) and large cell components. The tumor mass was treated with a low-dose radiation therapy (4Gy in 2 fractions) with a complete disappearance of diplopia within one week. At 2-year follow-up, patient was in complete remission. To the best of our knowledge, this is the first case of mixed component follicular and large components orbital lymphoma managed by first-intent low-dose radiation therapy.

JC human polyomavirus is associated to chromosomal instability in peripheral blood lymphocytes of Hodgkin's lymphoma patients and poor clinical outcome.

BACKGROUND: B cells are potential sites for latency and reactivation of the human neurotropic JC polyomavirus (JCV). We investigated JCV and Epstein-Barr virus (EBV) status in peripheral blood lymphocytes (PBL) from 74 Hodgkin's lymphoma (HL) and 91 B-cell non-Hodgkin's lymphoma (B-NHL) patients. PATIENTS AND METHODS: JCV and EBV DNA were assessed by PCR, and FISH technique was used to localize viral infection and to estimate chromosomal instability (rogue cells, 'chromosomal aberrations') throughout evolution. The influence of viral infection and chromosomal instability on freedom from progression (FFP) was investigated in HL patients. RESULTS: PCR product sequencing of PBL identified JCV in 42 (57%) circulating lymphocytes of HL patients. FISH analysis revealed that the presence of cells with a high JCV genome copy number--associated to the presence of rogue cells and 'higher frequency of chromosomal aberrations'--increased from 15% before treatment to 52% (P < 10(-5)) after. The co-activation of JCV and EBV was independent of known prognostic parameters and associated with a shorter FFP (JCV and EBV co-activation P < 0.001, rogue cells P < 0.002). CONCLUSION: In HL, JCV activation and chromosomal instability have been identified in PBL and associated with a poorer prognosis, especially in EBV+.

[A rare case of primitive prostatic large B-cell lymphoma and review of literature]. / Un cas rare de lymphome B diffus primitif de la prostate et revue de la littérature.

Primary malignant non-hodgkin lymphoma involving the prostate is rare. Most of the time, it is associated with extraprostatic disease. We report a case of a 72-year-old patient presenting with acute lower urinary tract irritative symptoms, due to large B-cell lymphoma limited to the prostate. Combination of chemotherapy with extern beam radiotherapy provided long-term local control.

Attenuated response of p53 and p21 in primary cultures of human prostatic epithelial cells exposed to DNA-damaging agents.

The multifocal origin of prostate cancer suggests a pan-organ defect in a tumor suppressor pathway. Although structural mutations in the p53 gene have been implicated in late-stage prostate cancer, little is known about the p53 response to genotoxic stress in normal human prostatic epithelial cells from which adenocarcinomas originate. We found that the majority (10 of 12) of epithelial cell cultures derived from histologically normal tissues of radical prostatectomy specimens failed to exhibit p53 accumulation in response to ionizing radiation. Epithelial cell cultures derived from benign prostatic hyperplasia and a primary prostatic adenocarcinoma also failed to accumulate p53 in response to ionizing radiation. In contrast, cultures of prostatic stromal cells derived from normal, benign prostatic hyperplasia, or adenocarcinoma tissues exhibited a 3-9-fold induction of p53 within 1-3 h after irradiation. Since p53 regulates a cell cycle checkpoint through the induction of the cyclin-cdk inhibitor p21, we examined p21 accumulation and cell cycle arrest following exposure to ionizing radiation. With one exception, epithelial cells that did not display increased p53 or p21 induction did not demonstrate a significant G1-S arrest in response to ionizing radiation, whereas stromal cells that accumulated p53 and p21 exhibited a large cell cycle arrest. These results indicate a functional difference between the DNA damage response of epithelial and stromal prostatic cells and suggest a possible mechanism for the increased susceptibility of prostatic epithelial cells to accumulate genetic alterations.

Is tumor cell radiation resistance correlated with metastatic ability?

Patients who experience local failure following radiation treatment of epithelial malignancies exhibit a substantially higher rate of distant metastasis than those patients who achieve permanent local control. This fact has raised concern that the local failure to control the primary/regional tumor may serve as a marker of a particularly malignant neoplasm, i.e., high metastatic activity and radiation resistance. If this were true, there would be no gains in survival by increasing the efficacy of treating the primary/regional disease because the new local controls would develop distant metastasis. To investigate this concept, the relationship between distant metastasis probability and tumor cell radiation resistance has been studied by examining laboratory and clinical data (in vitro and in vivo assays) from six collaborating centers. TCD50s (radiation dose which inactivates half of the irradiated tumors) and incidence of distant metastasis in mice with local control have been evaluated for 24 murine tumor systems. SF2s (surviving fraction after 2 Gy) were determined in vitro for cell lines from 8 human, 13 mouse, and 15 rat tumors/tumor sublines and the metastatic activity assessed after injection of the cells into syngeneic murine hosts and xenogenic hosts for the human tumors. SF2s of cells from carcinomas of the head/neck, cervix, and endometrium which were controlled locally by radiation +/- surgery from four centers were compared for those which did and those which did not metastasize. The total number of patients studied was 222. The cumulative distributions of SF2s of locally controlled tumors which did and did not metastasize were not different in each of the data sets. Similarly, there was no demonstrable relationship between TCD50s and metastatic frequency in local control mice. Furthermore, the SF2s of murine and human tumor cell lines did not track with metastatic activity. Radiation sensitivity of clinical and laboratory tumors did not correlate with metastatic activity in studies of data from six centers.

Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies.

PURPOSE: Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules. PATIENTS AND METHODS: Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI. RESULTS: One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors. CONCLUSION: The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group.

Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx.

Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period. Median age was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70 Gy) before 1980 and combination chemotherapy after 1980. Six patients were treated with first-line radiotherapy and they achieved complete remission (CR). Two subsequently received combination chemotherapy. Five of those patients remained in complete remission, after 97+ to 277+ months. Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases, and COP in five cases. Only three of them achieved CR, five had partial response and four had progressive disease. Five of the seven patients treated with CHOP did not achieve complete remission. The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR. Finally, two patients were treated with alternated chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+ months. Median survival was not reached in patients who received front-line radiotherapy, and was 35 months in patients who received front-line chemotherapy. These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to give favorable results, whereas its results are poorer when administered after resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy, or alternated chemotherapy-radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospectively in this type of NHL.

[Radiation treatment in non Hodgkin's lymphomas: present and future directions]. / Les traitements par les radiations ionisantes dans les lymphomes. Indications actuelles et futures.

Presently, radiotherapy is rarely an upfront treatment in patients with lymphomas. The modern evolution of radiation treatment calls for the development of therapeutic niches in which radiotherapy remains absolutely necessary. The development of new imaging techniques and their use in radiation planning systems along with new sophisticated radiation delivery techniques such as IMRT and respiratory gating should permit an increased accuracy an increased accuracy in the treatment of tumor masses and a decrease in late normal tissue complications.

Telomere shortening: a new prognostic factor for cardiovascular disease post-radiation exposure.

Telomere length has been proposed as a marker of mitotic cell age and as a general index of human organism aging. Telomere shortening in peripheral blood lymphocytes has been linked to cardiovascular-related morbidity and mortality. The authors investigated the potential correlation of conventional risk factors, radiation dose and telomere shortening with the development of coronary artery disease (CAD) following radiation therapy in a large cohort of Hodgkin lymphoma (HL) patients. Multivariate analysis demonstrated that hypertension and telomere length were the only independent risk factors. This is the first study in a large cohort of patients that demonstrates significant telomere shortening in patients treated by radiation therapy who developed cardiovascular disease. Telomere length appears to be an independent prognostic factor that could help determine patients at high risk of developing CAD after exposure in order to implement early detection and prevention.

Single dose versus fractionated total body irradiation before bone marrow transplantation: radiobiological and clinical considerations.

PURPOSE: This present review is intended to evaluate the specific influence of fractionation of total body irradiation on the outcome of a subsequent bone marrow transplantation. METHODS AND MATERIALS: Available experimental and clinical data on the influence of fractionation on leukemia cell killing, immunosuppression, and sparing of normal tissues were analyzed. RESULTS: Review of available data shows: (a) The role of fractionation on leukemia cell killing may vary with the leukemia type. For acute nonlymphoblastic leukemia, a few experimental and several clinical studies show no or little fractionation effect; a 12-13 Gy fractionated scheme could, therefore, be more efficient than a conventional 10 Gy single dose total body irradiation. For chronic myelogenous leukemia, some sensitivity to fractionation is suggested, so that an increase in total or fractional dose may be necessary in fractionated schemes to equate the efficacy of a 10 Gy single dose. For acute lymphoblastic leukemia, a high fractionation sensitivity was observed for some leukemic cell lines in vitro, without undisputable clinical confirmation for the moment. (b) Numerous experimental studies have demonstrated that the immunosuppressive effect of total body irradiation, a major determinant of engraftment, is highly fractionation sensitive. In humans, high rates of graft failures have been reported when T-cell depletion of the graft was associated to fractionated total body irradiation schedules. (c) A large amount of radiobiological and clinical data have demonstrated that late radiation-induced injuries to normal tissues and organs are highly fractionation sensitive. However, in a context of total body irradiation for bone marrow transplantation, the number of other determinants of normal tissue damage makes it difficult to demonstrate a clear-cut advantage of fractionated over single dose scheme, with a possible exception for children. CONCLUSIONS: In 1994, available data suggest that very cautious attempts could be made to adapt total body irradiation schedules to the potential normal tissue toxicity, T-cell depletion, and to the type of leukemia.

Consequences of two different doses to the lungs during a single dose of total body irradiation: results of a randomized study on 85 patients.

PURPOSE: To evaluate the incidence of lung complications and leukemia recurrences after two different doses to the lungs during total body irradiation. METHODS AND MATERIALS: Seventy-nine patients with acute leukemia (AML or ALL) in first complete remission or chronic myeloid leukemia in the chronic phase, five patients with high grade lymphoma, and one with chronic lymphocytic leukemia were entered in the study. They were given a single dose of total body irradiation (10 Gy over 4 h) with two different doses to the lungs (6 Gy or 8 Gy) prior to bone marrow transplantation. The median dose rate was 0.04 Gy/min. The median follow-up for both groups of patients was 24 months. RESULTS: The actuarial 5-year overall survival rate was similar in both groups, 59% and 43% for patients given 8 Gy and 6 Gy to the lungs, respectively. The lung complication rate was similar in the two groups (28% vs. 22% for the 8 Gy and 6 Gy group, respectively). The actuarial leukemia recurrence rate was significantly higher in the group of patients given 6 Gy to the lungs (25%) vs. 0% in the 8 Gy group. Interestingly, all recurrences occurred in the group of patients who were given 6 Gy to the lungs, who had acute leukemia, and no chronic graft vs. host disease (GVHD). CONCLUSIONS: Although the number of patients was not very large and the follow-up relatively short, these findings suggest that a lower dose to the lungs could lead to an increased incidence of leukemia recurrences due to a lower dose to the thoracic wall or to lower incidence of chronic GVHD.

Overall treatment time in advanced cervical carcinomas: a critical parameter in treatment outcome.

PURPOSE: To search for possible influence of overall treatment time on the clinical outcome of advanced cervical carcinomas treated with radiation alone. METHODS AND MATERIALS: Three hundred and eighty-six patients with Stage IIB and III cervical carcinomas treated with external radiation and intracavitary curietherapy between 1973 and 1983 were entered in the study. A multivariate analysis was carried out on data concerning these patients to determine whether overall treatment time was a prognostic factor. RESULTS: Overall treatment time and blood transfusions during treatment were the two most highly significant factors in the multivariate analysis. Loss of local control and overall survival, when treatment exceeded 52 days, was approximately 1% per day in both cases. CONCLUSION: These results suggest that overall treatment time might be a highly significant prognostic factor in the treatment outcome of advanced cervical carcinomas. Prospective randomized studies are strongly warranted to confirm this hypothesis.

Thallium-201 scintigraphy is not predictive of late cardiac complications in patients with Hodgkin's disease treated with mediastinal radiation.

PURPOSE: To assess whether abnormalities depicted by Thallium-201 scintigraphy can predict the occurrence of late cardiac complications in patients with Hodgkin's disease treated with mantle field radiation therapy. METHODS AND MATERIALS: Thallium scintigraphy was performed in 49 patients at a median of 75 months after initial treatment (range 28-208 months). Initial treatment consisted in chemotherapy, given to two-thirds of the patients and mantle field radiation, delivered to all patients, using a 25-MV linear accelerator. Myocardial perfusion defects were observed in 78% of patients on thallium scintigraphy. These patients had their cardiac status reassessed at a median follow-up of 13.5 years after treatment. RESULTS: Forty-two patients were assessable, as data on the cardiac status were missing in 7 patients. The majority of patients received at least 40 Gy, and 75% of them were treated with one field per day. The median follow-up of patients is 13.5 years (range 9-24.5). Eleven cardiac complications were observed in 9 patients (coronary artery disease [n = 2], conduction-system abnormalities [n = 3], valvular defects [n = 5], and congestive heart disease [n = 1]). The median 15-year actuarial incidence of cardiac complications was 21% (95% confidence interval of 9-40%). The positive and negative predictive value of thallium scintigraphy was 19% and 77%, respectively. The univariate analysis showed that the extent of left ventricle exposure to irradiation was an adverse prognostic factor, and chemotherapy administered before mantle field irradiation was of borderline significance. CONCLUSION: Thallium scintigraphy is not predictive of late cardiac complications. The extent of left ventricle exposure to radiation and possibly chemotherapy given before radiation treatment are adverse prognostic factors.

Predictive value of in vitro radiosensitivity parameters in head and neck cancers and cervical carcinomas: preliminary correlations with local control and overall survival.

PURPOSE: To determine whether in vitro radiosensitivity parameters are predictive of treatment outcome. METHODS AND MATERIALS: Biopsies were obtained from patients with head and neck cancers (57) and cervical carcinomas (20) and in vitro radiosensitivity parameters were obtained using the CAM plate assay. RESULTS: In most cases (75%) patients were treated with radiation alone. The median follow up was 461 days. When the whole group of head and neck cancers and cervical carcinomas was considered, patients with a SF2 value below 0.36 had a higher 2-year local control rate (93% versus 68%) and a higher 2-year survival rate (71% vs. 62%) than those with SF2 values above that threshold, but differences were not significant. These trends persisted when head and neck cancers were considered alone with a higher local control rate (86% vs. 67%) and a higher survival rate (75% vs. 52.5%) obtained for patients with a SF2 value below 0.36. When the alpha value was evaluated for the whole group of patients a significantly higher local control rate (80.5% vs. 40.5%) and overall survival rate (71% versus 37.5%) at 2 years were obtained for patients with alpha values above 0.07 Gy-1. When only the group of head and neck cancers was considered, local control rate was significantly higher (79% vs. 33%) but overall survival rate (65.5% vs. 33%) was not significantly higher for alpha values above 0.07 Gy-1. CONCLUSION: These results are encouraging but need to be confirmed with a larger number of patients with a longer follow-up.

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de moelle osseuse (GEGMO).

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.

Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation.

PURPOSE: Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. METHODS AND MATERIALS: Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. RESULTS: T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry, all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation; that is, CD3+4+45RO+, CD3+4+45RA+, CD3+4+8-, CD3+4-8+. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3-, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. CONCLUSION: Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation.

In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: cell characterization and correlations with local control and overall survival.

PURPOSE: To determine whether in vivo parameters (surviving fraction at 2 Gy, alpha values, and calculated cell growth fraction) were predictive of the treatment outcome. METHODS AND MATERIALS: Biopsies were obtained from patients with a head and neck tumor. In vitro parameters were determined using the CAM plate assay. Cell characterization by cytogenetic analysis was performed on 19 different cell cultures. In 25 additional cell cultures, cell clonogenicity was tested using the Courtenay Mills assay. RESULTS: Biopsies were obtained from 156 patients with a head and neck tumor and the oropharynx was the predominant primary site. In vitro parameters were obtained in 113 cases (72%) (SF2 in 93 cases and calculated cell growth fraction in 103 cases). Cell characterization showed that cells in CAM plates were diploid with no clonal chromosome abnormalities and gave colonies in soft agar with a mean cloning efficiency of 1.610(-3). Only patients treated with surgery and/or radiation (76), were considered eligible for in vitro parameters and treatment outcome correlation studies. The mean follow-up is over 2 years (range 9-47 months). The local control rate was significantly higher (p = 0.04) for patients with alpha values above the cut-off point of 0.07 Gy-1 (69% vs. 38% at 2 years). The local control rate was also significantly higher (p = 0.04) for patients with calculated cell growth fraction values about the cut-off point of 0.06% (70% vs. 48% at 2 years). Moreover for these latter patients the overall survival rate was also significantly higher (p = 0.004) (54% vs. 26% at 2 years). It is worth noting that alpha and calculated cell growth fraction values below the cut-off points identified a small group of patients (about 20%) who were at a significantly high risk of local failure. From a pragmatic point of view, as only radiosensitivity or calculated cell growth fraction values could be obtained in a certain number of experiments due to technical reasons, the treatment outcome of patients who had either alpha and/or calculated cell growth fraction values below the cut-off levels (about 30% of all patients) was analyzed. This group of patients fared significantly worse (p = 0.02) in terms of local control (50% vs. 68% at 2 years) and (p = 0.04) overall survival (36% vs. 50% at 2 years). CONCLUSION: These results suggest that in vitro parameters using the CAM plate assay, might be useful in predicting the treatment outcome of patients with a head and neck tumor treated with surgery and postoperative radiation, or radiation alone. However, they must be considered as preliminary because the cut offs used in the study were chosen for exploratory purposes. Only a multivariate analysis including all clinical and biologic factors will allow us to draw any firm conclusions.

Accelerated fractionation in esophageal cancers: a multivariate analysis on 88 patients.

PURPOSE: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival. METHODS AND MATERIALS: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days. RESULTS: The 3-year actuarial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control. CONCLUSION: These findings suggest that accelerated fractionation given in an overall treatment time of <35 days might be beneficial for early-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with moderate acute and late toxicity.

Baseline and treatment-induced chromosomal abnormalities in peripheral blood lymphocytes of Hodgkin's lymphoma patients.

PURPOSE: To study chromosomal abnormalities in 49 patients with Hodgkin's lymphoma (HL), before and after treatment and at several times during a 2-year period. METHODS AND MATERIALS: Simple chromosomal aberrations (CAs) and complex chromosomal rearrangements (CCRs) were counted in peripheral lymphocytes by painting of chromosomes 1, 3, and 4 (fluorescence in situ hybridization). A control population was composed of 20 healthy donors and 69 untreated cancer patients who had undergone various radiologic scans. RESULTS: A greater frequency (p < 10(-4)) of spontaneous cytogenetic abnormalities was observed in untreated HL patients compared with the control populations. CCRs were observed exclusively in the HL population (p < 10(-4)). Chemotherapy was associated with a significant increase in the frequency of CAs (p < 10(-4)), according to the chemotherapy regimen (p = 0.002). Immediately after radiotherapy, a significant increase (p < 10(-4)) was observed in CAs according to the size of the irradiation field. Conversely, the significant increases in the frequency of CCRs observed after treatment did not correlate with the chemotherapy regimens, radiotherapy dose, or size of the irradiation field. The evolution of CAs vs. CCRs over time was also dissociated: during the follow-up of these patients, a significant decrease was observed in the frequency of CAs at 6 months and 1 and 2 years. In contrast, after an initial decrease for up to 6 months after treatment, the frequency of CCRs remained constant for up to 2 years. CONCLUSION: Increased cytogenetic abnormalities were observed in untreated HL patients compared with the control populations. The greater frequency of cytogenetic abnormalities persisted in some patients. The presence of CCRs supports the concept of a unique genetic environment in HL patients that persists in response to potentially noxious treatments.

A high and sustained response rate in refractory or relapsing low-grade lymphoma masses after low-dose radiation: analysis of predictive parameters of response to treatment.

PURPOSE: To determine the efficacy of small doses of radiation in patients with recurrent or refractory low-grade lymphoma masses. METHODS AND MATERIALS: Patients with refractory or relapsing low-grade lymphoma masses. The two largest diameters of the tumor mass were measured, whenever possible, before and after treatment. A dose of 4 Gy of radiotherapy was delivered to tumor sites in 2 fractions. Patients were evaluated for response 1-4 months later and at regular follow-up visits. RESULTS: Forty-eight patients with low-grade lymphomas according to the working formulation received low-dose radiotherapy between March 1987 and November 1998. Most patients had advanced disease at the time of radiation treatment, and 80% had received at least two chemotherapy regimens before treatment. The median interval between the initial diagnosis and radiotherapy was 2.7 years (range 0-22 years). Low-dose radiation was delivered to 135 tumor sites. Nodal and extranodal tumor sites represented 80% and 20% of masses, respectively. An objective response was obtained in 81% of the sites, with 57% attaining a complete remission. The 2-year actuarial freedom from local progression (FFLP) rate was 56% (95% CI, 46-66%). Tumor masses 5 cm), the number of chemotherapy regimens (0-1 vs. more), and age at time of radiation treatment (< or =65 years or > 65 years) were significant predictive parameters of response to treatment. CONCLUSIONS: In this retrospective study, low-dose radiation proved efficient, with long-lasting effects in the majority of patients with recurrent or refractory low-grade lymphomas. This simple and nontoxic treatment should be investigated prospectively in patients with advanced disease and a low tumor burden not immediately warranting chemotherapy.