Henric Blomgren

Anaplastic Giant Cell Carcinoma of the Thyroid Gland: Treatment and Survival Over a 25-Year Period

Abstract. Anaplastic giant cell carcinoma of the thyroid is a rare but highly malignant tumor. At the Karolinska Hospital in Stockholm, surgery, chemotherapy, and radiotherapy have been used separately or in various combinations in 81 patients admitted with this diagnosis during 1971–1997. In this study, we present the various multimodality treatment regimens and their changes over the years and the subsequent differences in survival and local tumor control. Overall, eight patients (10%) survived more than 2 years. All survivors were treated with combinations of chemotherapy, radiotherapy, and surgery. Among the patients who died, local tumor control was achieved by the therapy given in many cases. The results suggest that our current strategy with a combination of preoperative hyperfractionated accelerated radiotherapy, doxorubicin pre- and postoperatively, and debulking surgery whenever possible results in better local tumor control and an increased chance of survival.

Stereotactic body radiotherapy of primary and metastatic renal lesions for patients with only one functioning kidney

Background. About 2% of patients with a carcinoma in one kidney develop either metastases or a new primary tumor in the contralateral kidney. Often, renal cancers progress rapidly at peripheral sites and a metastasis to the second kidney may not be the patients main problem. However, when an initial renal cancer is more indolent yet spreads to the formerly unaffected kidney or a new primary tumor forms there, local treatment may be needed. Stereotactic body radiotherapy (SBRT) has been demonstrated as a valuable treatment option for tumors that cause local symptoms. Presented here is a retrospective analysis of patients in whom SBRT was used to control primary or metastatic renal disease. Patients and methods. Seven patients with a mean age of 64 (44–76) were treated for metastases from a malignant kidney to its contralateral counterpart. Dose/fractionation schedules varied between 10 Gy×3 and 10 Gy×4 depending on target location and size, given within one week. Follow-up times for patients who remained alive were 12, 52 and 66 months and for those who subsequently died were 10, 16, 49 and 70 months. Results. Local control, defined as radiologically stable disease or partial/complete response, was obtained in six of these seven patients and regained after retreatment in the one patient whose lesion progressed. Side effects were generally mild, and in five of the seven patients, kidney function remained unaffected after treatment. In two patients, the creatinine levels remained moderately elevated at approximately 160 µmol/L post treatment. At no time was dialysis required. Conclusion. These results indicate that SBRT is a valuable alternative to surgery and other options for patients with metastases from a cancer-bearing kidney to the remaining kidney and provides local tumor control with satisfactory kidney function.

Blood lymphocytes in breast cancer patients following radiotherapy and surgery

Abstract Peripheral blood lymphocytes from 110 subjects with primary carcinoma of the breast were studied before and at various times after local radiotherapy and/or surgery. The results demonstrated that the recovery of the relative PPD (purified protein derivative) responses of the lymphocytes after radiotherapy progresses more rapidly than the repopulation of the total lymphocyte population.

Evidence for the appearance of non-specific suppressor cells in the blood after local radiation therapy.

Radiation therapy for carcinoma of the breast may induce lymphopenia and a reduction of the purified protein derivative (PPD) tuberculin reactivity of the lymphocytes in vitro as measured on a cell-for-cell basis. In the present investigation we have examined whether the reduced PPD-reactivity after irradiation can be explained by the appearance of non-specific suppressor cells. The results confirm that the reactivity of non-purified lymphoid cell preparations decreases significantly after radiotherapy. This reduction was not correlated to the extent of radiation induced lymphopenia. In contrast, lymphoid cell preparations depleted of adherent cells do not exhibit any significant decrease, indicating that monocytes-macrophages may become non-specifically immunosuppressive after local radiotherapy.

Hypocholesterolemia in cancer patients may be caused by elevated LDL receptor activities in malignant cells

Several epidemiological studies indicate an inverse relation between plasma cholesterol and the occurrence of cancer. Since we in previous studies have found that certain malignant cell types have an elevated LDL receptor activity, the aim of the present study was to further explore the possibility that an elevated LDL consumption by tumor cells causes hypocholesterolemia. The plasma cholesterol concentrations in patients with acute leukemia were inversely correlated with the rate of receptor-mediated degradation of125I-LDL by the leukemic cells. During chemotherapy, the total plasma and the LDL cholesterol levels increased concomitantly with the reduction in the leukemic cell count in a patient whose leukemic cells exhibited a high rate at receptor-mediated degradation of125I-LDL. In certain patients with inoperable urinary bladder carcinoma, the plasma cholesterol concentration fell as the disease progressed. Studies in breast cancer patients indicate that the number of LDL receptors in the tumor tissue may have prognostic significance. The results are in agreement with the hypothesis that an elevated LDL receptor activity in malignant cells may lead to hypocholesterolemia.

Reductions of responder and stimulator capacities of peripheral lymphoid cells in the mixed lymphocyte culture following external radiotherapy.

The peripheral lymphoid cells of patients with primary cancers of the breast, urinary bladder or prostate were examined, before and after radiotherapy, for capacity to respond and stimulate in the mixed lymphocyte culture using lymphoid cells from healthy donors as allogeneic cells. Radiotherapy reduced both the responder and stimulator capacities of the peripheral lymphoid cells to approximately the same extent in the same individual. These reductions were not correlated to the extent of radiation induced lymphopenia. The results suggest a general defect of the peripheral lymphoid cell population after radiotherapy.

T lymphocyte subpopulations in blood following radiation therapy for breast cancer

T helper and T suppressor lymphocyte subpopulations were examined before and after postoperative adjuvant radiation therapy for breast cancer. Absolute numbers of all T cell subsets were reduced by 70-80%. The proportion of IgG-Fc receptor-bearing T cells (Tg cells) was significantly reduced and that of IgM-Fc receptor-bearing T cells (Tm cells) significantly increased at completion of local radiation therapy with 45 Gy (4500 rad). Proportions of T suppressor (Ts) and T helper (Th) cells determined by monoclonal antibodies were not changed by radiation therapy. The overlapping between Tg and Ts subpopulations was 20-30% as examined by double labelling.

Blood Lymphocytes After Radiation Therapy of Carcinoma of Prostate and Urinary Bladder

(1974). Blood Lymphocytes After Radiation Therapy of Carcinoma of Prostate and Urinary Bladder. Acta Radiologica: Therapy, Physics, Biology: Vol. 13, No. 4, pp. 357-367.

Natural Killer Activity in Peripheral Lymphocyte Population Following Local Radiation Therapy

The natural killer (NK) activity of peripheral lymphocytes against 51Cr-labelled Chang or K562 cells was tested using a 4 h release assay before and after postoperative radiation therapy for mammary carcinoma. NK activity against K562 was significantly reduced at completion of therapy (a total target dose of 45.0 Gy) and restituted 3 to 4 months later. NK activity against Change cells exhibited a slight but non-significant decline at completion of therapy followed by an overshoot 3 to 4 months later. The frequency of Fc-IgG receptor bearing lymphocytes was decreased at completion of therapy and largely restored after 3 to 4 months.

Lymphopenia and metastatic breast cancer patients with and without radiation therapy

Abstract Peripheral blood lymphocytes from patients with breast cancer were examined at the time of discovery of distant metastases with respect to lymphocyte counts and stimulation in vitro by PPD tuberculin and phyto-haema glutinin (PHA). The results were compared to those obtained at corresponding time in patients still free of metastases. Lymphocyte counts and stimulability to PPD and PHA were significantly lower in patients examined in connection with the discovery of metastases than m patients free of metastases. The possible mechanisms underlying impaired lymphocyte reactivity are discussed.