Gerard Socie

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.

Epidermoid carcinoma of the anal canal treatment results and prognostic variables in a series of 242 cases

UNLABELLED From 1972 to 1985, 260 cases of anal canal epidermoid carcinoma were irradiated. Eighteen cases treated for palliation were excluded from the study; 242 (93%) were treated with curative intent. The sex ratio was 1/5.5; mean age was 66 years. HISTOLOGY 60.3% were well differentiated epidermoid carcinoma; 31.0% moderately differentiated and 8.7%, cloacogenic cases. Staging: T1: 11.5%; T2: 16.1%; T3a: 17%; T3b: 33.5%; and T4: 21.9%. Abnormal inguinal nodes were present in 15.3% of cases. Crude overall survival (Kaplan-Meier) for the 242 cases is 86.4% at 1 year, 63.9% at 3 years, 51.2% at 5 years, and 30.8% at 10 years. Radiation therapy was the sole treatment for 193 cases. No chemotherapy was given. Patients were irradiated by external beam. They received a first course of X rays (mostly 18 MV, some 6 MV) 40 to 45 Gy (box technique) over 4 to 5 weeks in the pelvis. Age and size of tumor were considered when deciding on the target volume. After a rest period of 4 to 6 weeks, a second course of 15 to 20 Gy in 2 weeks was given through a perineal field by electron-beam of suitable energy. The mean total dose was 60.56 Gy and median was 62.5 Gy; the mean overall treatment duration was 85.3 days (median 82 days) and the mean Time Dose Factor including decay factor was 98.96. In this group, 5-year determinate survival was: T1-T2, 84.5%; T3a, 74.8%; T3b, 64.9%; T4, 58.9%. In 147/193 patients (76.2%) local control was achieved. The overall anal conservation rate was 62.6%. In 106 cases (55%), the anus had maintained normal function. The 5-year survival rate by N was 73.3% in the absence of inguinal nodes (169 cases) and 36.1% if such nodes were present. There was no significant difference in survival rate according to histological type. In the second group, receiving radiation therapy plus surgery, 33/49 cases (T3b-T4) were irradiated before surgery (median dose 40.5 Gy). Post operative radiation therapy was administered in 16 cases (T3b-T4) (median dose 49.6 Gy). The 5-year determinate survival is 53.2% for T3b and 79% for T4. According to the log-rank test, there was no significant difference between survival with radiation therapy alone and radiation therapy plus surgery. Multivariate analysis of the whole group indicated that T stage is the only predictive variable.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia

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.

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.

Post-irradiation hyperamylasemia as a biological dosimeter

Serum alpha-amylase was measured before and 24 h after either total body (31 patients) or localized irradiation including the salivary glands (40 patients) or the pancreatic area (22 patients). A significant increase in amylasemia was observed for doses to the parotid glands larger than 0.5 Gy. A sigmoid function of dose was fitted to the data and predicted a maximum amylasemia level for doses larger than 4 Gy and smaller than 10 Gy. The raw data from other published series were adequately described by the same model. However, the confidence limits of the parameters remained wide, because of a considerable interindividual variability. Post-irradiation hyperamylasemia appears to provide a good criterion for triage of accidentally irradiated patients: 24 h after a dose larger than 2 Gy to the parotid glands, 91% of the patients had an amylasemia level higher than 2.5-fold the upper normal value (sensitivity). Conversely, 96% had their serum amylasemia lower than 2.5-fold the upper normal value when dose was smaller than 2 Gy (specificity). However, a retrospective estimation of the absorbed dose (dosimetry) is not likely to be very precise because of the large interindividual variability.

Follow-up thallium-201 scintigraphy after mantle field radiotherapy for Hodgkin's disease.

PURPOSE Assessment of the long-term cardiac effects of mediastinal radiotherapy for Hodgkins disease, by Thallium scintigraphy. METHODS AND MATERIALS 32 patients (14 males and 18 females) who underwent mantle field radiotherapy for Hodgkins disease were included in this study. Twenty patients received 4 fractions of 2.5 Gy per week and 12, five fraction of 2 Gy per week, delivered on alternate days. All the patients, except three, performed exercise testing electrocardiogram and Thallium-201 tomoscintigraphy. The average time interval from completion of treatment to the study was 7 years (range 3-13 years). No patients had clinical symptoms of cardiac disease. Mean age at the time of the study was 35 years (range 23-48 years). RESULTS Two electrocardiograms revealed left bundle branch block and the patients were excluded from the study. Only one out of 27 exercise electrocardiograms was abnormal in a patient with mitral valve prolapse, who was also excluded from the study. Twenty-six scintigraphies were evaluable. Twenty-two (85%) were clearly abnormal with partial or complete redistribution on delayed images. The anterior region was affected in 19 of these cases (86%). Four explorations were undoubtedly normal. Coronary angiography was not performed for ethical reasons in these asymptomatic patients. CONCLUSION Despite possible false positive tests, the high rate of abnormality (85%) in this small series is striking. These preliminary data justify larger studies and a close long-term follow-up of these patients.

Secondary solid malignant tumors occurring after bone marrow transplantation for severe aplastic anemia given thoraco-abdominal irradiation

PURPOSE We have evaluated irradiation doses received at location of secondary solid tumors occurring after bone marrow transplantation (BMT) in five of 147 patients grafted for severe aplastic anaemia. RESULTS All 5 tumors occurred within the radiation field penumbra. The estimated received dose varied from 6 Gy for one inner field secondary tumor, to 2.5 Gy for the remaining secondary tumors. CONCLUSION Tumors may arise in the zone where the delivered radiation dose drops dramatically. Irradiation, with associated cofactors, may promote the development of epidermoid carcinoma in irradiated patients for BMT.

Pulmonary Involvement in Patients with Hematological Malignancies: And Now?

Many of us remember the time when we had to warm up the blood gas analyzer, use polymyxin methylene sulfonic acid as the antibiotic of last resort, fear chicken pox like the plague, and wait for the autopsy results to diagnose most cases of cytomegalovirus or Aspergillus spp. pneumonia. We remember what it was like before computed tomography, magnetic resonance imaging, positron emission tomography, and molecular biology. Since then, 30 years have elapsed, although it feels more like a century. In those days, providing care to a hematology patient was not for the faint of heart. Failure enveloped us in a dreadful solitude that was bearable only because our occasional successes (complete remissions with hope for a cure) brought a profound sense of joy. We seem to recall feeling like the Lone Ranger, prepared to take on the enemy single-handed. The solitude, or rather the self-imposed isolation, was very real. We thought we were the only ones who “knew.” We worked closely with the pathologists, cytologists, and geneticists, but we categorized our other colleagues (pulmonologists, gastroenterologists, nephrologists, radiologists, microbiologists, etc.) as mere service providers. We suspected the infectious disease specialists of not understanding our patients or, even worse, of not being interested in them, and we called in the intensivists only when all else had failed.

Clinical Pathology and natural history of PNH; The French Society of Hematology experience.

Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder caused by PIG-A gene alterations. In contrast to the growing knowledge regarding the pathophysiology of the disease, data on factors influencing survival are scarce, mainly as a result of the rarity of the disease. Data on 220 patients, diagnosed with PNH over a 46-year period in reporting French centers, were collected. Kaplan-Meier survival estimates (mean +/− standard error) were 65±4% and 48±6% at 10 and 15 years after diagnosis, respectively. In this cohort of 220 patients with PNH, aplastic anemia (AA) antedated PNH in 65 patients with a median interval of 3.1 years. These 65 patients with an AA-PNH syndrome were shown to have a relative risk (RR) of death 3 times lower than the remaining 155 patients with de novo PNH. Finding a better prognosis among patients with AA before diagnosis of PNH might be surprising, we thus reassessed, the differences between the AA-PNH syndrome and de novo PNH. Age, gender and symptom distributions were similar in both groups, at diagnosis. However, when comparing these patients at presentation, anemia was less frequently, but thrombopenia and neutropenia were more frequently observed. Patients with the AA-PNH syndrome were more frequently treated initially with androgens or immimosuppressive therapy than those with de novo PNH. During follow-up, the prevalence or cumulative incidence of main complications was similar in both groups. Multivariate analysis showed that 5 factors influenced survival in both groups (thrombosis, MDS or acute leukemia, age over 54 years, thrombocytopenia at diagnosis and mitial treatment other than androgens), while 1 factor (pancytopenia durmg the evolution) increased the risk of death in patients with de novo PNH. Treatment other than androgens led to an increased risk of death (∼ 5 fold) in patients with de novo PNH while it lowered the risk of death (∼ 4 fold) in patients with the AA-PNH syndrome, compared to patients treated by androgens in either group.