Reinier Somers

Long-Term Risk of Second Malignancy in Survivors of Hodgkin’s Disease Treated During Adolescence or Young Adulthood

PURPOSE To quantify the long-term risk of second primary cancers (SCs) in patients diagnosed with Hodgkins disease (HD) during adolescence or young adulthood. PATIENTS AND METHODS The risk of SCs was assessed in 1,253 patients diagnosed with HD before the age of 40 years and treated in two Dutch cancer centers between 1966 and 1986. The median follow-up duration was 14.1 years. RESULTS In all, 137 patients developed SCs, compared with 19.4 cases expected on the basis of incidence rates in the general population (relative risk [RR] = 7.0; 95% confidence interval, 5.9 to 8.3). The 25-year actuarial risk of SC overall was 27.7%. The RR of solid tumors increased greatly with younger age at the first treatment of HD, not only for breast cancer but also for all other solid tumors, with RRs of 4.9, 6.9, and 12.7 for patients first treated at ages 31 to 39 years, 21 to 30 years, and </= 20 years, respectively. Among patients first treated at the age of 20 years or younger, the RR of developing a solid tumor before the age of 40 years was significantly greater than the RR of solid tumor development at ages 40 to 49 years (RR = 27.9 v RR = 4.2; P =.0001). Patients who received salvage chemotherapy had significantly greater risk of solid cancers other than breast cancer than did patients whose treatment was restricted to initial radiotherapy or initial combined-modality treatment (RR = 9.4 and 4.7, respectively; P =. 004). CONCLUSION After more than 20 years of follow-up, the risk of solid tumors is still much greater in survivors of HD than in the population at large. Reassuringly, the greatly increased risk of solid tumors in patients who were young (</= 20 years of age) at the first treatment seems to decrease as these patients grow older. Our data suggest that chemotherapy may increase the risk of solid tumors from radiotherapy.

Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody

SummarySix patients with progressive B cell non-Hodgkins lymphoma have been treated with an IgG2a mouse monoclonal antibody (mAb) against the B cell differentiation antigen CD19, with total doses varying from 225 mg to 1000 mg. Free mAb was detected in the serum after doses of 15–30 mg. After the mAb infusions the number of circulating tumour cells was temporarily reduced, but in some cases antibody-coated cells remained in the circulation for several days. mAb penetrated to extravascular tumour sites; in general higher doses were required to saturate cells in the lymph nodes than to sensitize tumour cells in the bone marrow. mAb doses of up to 250 mg were given i.v. over 4 h without major toxicity. One patient twice achieved a partial remission after two periods of mAb treatment with an 8-month interval; the second remission lasted for 9 months. One patient showed a minor response. None of the patients made antibodies against the mouse immunoglobulin. Serum immunoglobulin levels were followed as a measure of the function of the normal B cell compartment; no significant changes were seen up to 6 months after mAb treatment.

Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma

Treatment results of leptomeningeal metastasis are reported in 33 breast cancer patients. They were divided into three groups: group 1, 19 patients, received intraventricular methotrexate (MTX) with doses based on CSF MTX levels; group 2, 6 patients, received whole brain radiation followed by a course of MTX given by lumbar punctures; group 3, 8 patients, was not treated. Median survival in group 1 was 6 months; 25% survived 1 year or more. Median survival (1 to 2 months) in groups 2 and 3 was significantly shorter. Neurologic improvement was seen in an average time of 4 weeks in about 80% of group 1 patients. Two of group 2 patients improved at 3 weeks, and all group 3 patients deteriorated. Carcinomatosis caused death significantly less often in group 1 than in the other groups.

Prognostic significance of the number of involved areas in the early stages of Hodgkin's disease

An analysis of 1059 patients with clinical stage (CS) I and II Hodgkins disease was undertaken to determine the prognostic significance of the number of involved sites. In this group of patients the number of involved lymph node areas was highly correlated with the probability of dissemination of occult disease. In the subgroup of patients with involvement of two lymph node sites (CS II2) approximately 50% demonstrated occult dissemination on the other side of the diaphragm as evidenced by subsequent relapse in the untreated subdiaphragmatic region. However, only 15% to 20% of this group had unsuspected disease in regions other than the spleen or the paraaortic lymph nodes. In CS I and II2 supradiaphragmatic patients, who underwent a staging laparotomy, splenic involvement was a powerful prognostic indicator. When the spleen was not involved, less than 10% of patients had disease elsewhere below the diaphragm, whereas, when the spleen was involved as many as 40% of patients had additional subdiaphragmatic sites involved. In the subgroup with three or more lymph node areas involved (CS II3), the proportion of patients with extension of disease on the other side of the diaphragm, as evidenced by later relapse was also about 50%. But in these patients, unlike the CS II2 patients, analysis of relapse patterns showed that occult disease had already disseminated to the pelvic nodes or to extra nodal sites. Furthermore, splenic involvement was of much less prognostic significance because CS II3 patients who did not demonstrate splenic involvement at staging laparotomy had similar relapse incidence and similar relapse patterns as those with positive spleens.

Erythrocyte Sedimentation Rate Predicts Early Relapse and Survival in Early-Stage Hodgkin Disease

Objective: To assess the value of an elevated (> 30 mm/h) Westergren erythrocyte sedimentation rate (ESR) for predicting early relapse and survival after therapy in patients with clinical stage I o...

Effective systemic therapy for spinal epidural metastases from breast carcinoma

A complete resolution of spinal epidural metastases following systemic therapy, consisting of chemotherapy and/or hormonal therapy, is reported in four patients with breast carcinoma. Remissions were of substantially longer duration than previous remissions induced by radiotherapy. Single systemic therapy is an underestimated way of treatment for spinal epidural metastases. This way of treatment should be considered when radiotherapy has failed. Under certain circumstances it might even be considered as primary treatment. The protracted remissions following systemic therapy, even in the case of a complete myelographic block, warrant further clinical studies concerning this mode of treatment.

Acute leukemia following therapy for teratoma

Three cases of acute leukemia are reported following aggressive therapy for inoperable germ cell tumors. Two patients were treated by radiation plus cytotoxic chemotherapy and the third received only drugs. The time between onset of these therapies to death from leukemia was 4, 17 and 61 months.

Sequential non-cross-resistant chemotherapy regimens (MOPP and CAVmP) in Hodgkin's disease stage IIIB and IV

Fifty consecutive patients with advanced Hodgkins disease were treated in a multicentre study with 6 cycles of an alternating scheme of MOPP and CAVmP followed by irradiation to a dose of 20 Gy. The objective was to increase complete remission (CR) and cure rates by alternating two effective noncross‐resistant regimens with subsequent consolidation of the remission by irradiating bulky nodes. A total of 47 patients completed the treatment and are evaluable. In the first 13 patients the irradiation fields amounted to a total or subtotal nodal irradiation with inclusion of the spleen. In case of organ involvement the affected organ was also included in the irradiation field. The irradiation protocol was later changed to an irradiation of the initially involved sites because of severe leucopenia and thrombopenia. After completion of the chemotherapy 32 (68%) patients (for Stage IIIB and IV patients: 63% and 71%, respectively) achieved a CR, after ending the radiotherapy the percentage of CR increased to 87% (for stage IIIB and IV patients: 90% and 86%, respectively). Five of the patients relapsed in an irradiated and nonirradiated area, three patients in a nonirradiated field. The actuarial 3‐year survival rate for the entire group was 86% and for patients in CR 94%. The relapse‐free survival was 73%. It is concluded that this alternating chemotherapy scheme followed by irradiation is at least equally effective as MOPP treatment in achieving a CR, and is probably superior in terms of survival.

Reproducibility and prognostic value of different non-Hodgkin's lymphoma classifications: Study based on the clinicopathologic relations found in the EORTC trial (20751)

In the EORTC trial 20751, six pathologists belonging to five different centers classified tumoral lymph nodes from 406 untreated patients with non-Hodgkins lymphoma (NHL) into three different NHL classifications. NHL were most easily and reliably subdivided according to the growth pattern (the rate of consensus being 93%). Classification according to growth pattern proved to be of prognostic significance. The rate of consensus of classifying cases in the different NHL classifications ranged from 74% for the Rappaport, through 70% for the Kiel to 67% for the international working formulation. It is concluded that NHL are reliably classified according to their growth pattern, and that this subdivision is of primary prognostic significance.

Second Cancer Risk Following Testicular Cancer

Publisher Summary This chapter examines the second cancer risk following testicular cancer. As a result of the introduction of cisplatin-based combination chemotherapy, survival from nonseminomatous tumors of the testis has greatly improved. The long-term effect of modern, platinum-based CT on SC risk has not been examined much, since the follow-up period for such studies was still rather short. Vinblastine and bleomycin have not been associated with the development of second malignancies. Cisplatin has been shown to have carcinogenic potential in experimental studies. Also, the cytostatic agent etoposide, which is frequently used in platinum-based CT, is a strong mutagen that has recently been shown to have leukaemogenic potential in humans. There has been some concern regarding the development of second malignancies after administration of platinum-based CT. In the statistical analysis, a comparison was made between SC incidence among the testicular cancer patients and cancer incidence in the general population. In this person-years type of analysis, the ratio of the observed and expected number of SCs in the study population was determined. Expected numbers of SC were computed with the use of age, sex, and calendar year-specific incidence rates.