David S. Shimm

Merkel cell carcinoma. Improved locoregional control with postoperative radiation therapy.

Between April 1981 and May 1990, 11 patients with Merkel cell carcinoma were treated with radiation therapy in Tucson, Arizona. The length of follow‐up time from the time of irradiation ranged from 6 to 64 months. Locoregional control was maintained in seven of eight patients treated with surgery and postoperative radiation therapy for primary or recurrent cancer. The other three patients had bulky metastatic disease at the time of referral. Palliation was achieved in all three patients with radiation therapy. Hyperthermia also appeared to be beneficial in the one patient in which it was used, and chemotherapy achieved responses in two of four patients. These results, combined with a review of the literature, suggest that the administration of radiation therapy postoperatively to both the surgical bed and the draining lymph nodes improves locoregional control and may result in long‐term disease‐free survival when administered after the initial surgical resection.

Basal cell carcinoma treated with radiation therapy

Between 1974 and 1989, 85 patients with 115 biopsy‐proven basal cell carcinomas were treated with radiation therapy at the University Medical Center in Tucson. Either orthovoltage or megavoltage photons were used to deliver doses ranging from 2000 cGy in a single treatment to 7300 cGy in 35 fractions over 62 days. The median length of follow‐up was 40 months. Kaplan‐Meier estimates of the 5‐year local control rates are presented by American Joint Committee on Cancer stage. The difference between the local control rates for both previously untreated and recurrent Stage I and II carcinomas (95% at 5 years) and Stage III and IV carcinomas (56% at 5 years) was statistically significant (P = 0.0001, by Mantel‐Haensel test). Although recurrent basal cell carcinomas generally have a worse prognosis, the Kaplan‐Meier estimate of the 5‐year local control rate for recurrent Stage I and II carcinomas treated with radiation therapy was 95%. These results, along with a review of the literature, suggest two points: (1) high cure rates can be obtained when Stage I and II basal cell carcinomas are treated with radiation therapy and (2) radiation therapy is a relatively effective method for treating recurrent basal cell carcinomas, with cure rates surpassed only by Mohs micrographic surgery. Cancer 68:2134–2137, 1991.

Radiation Therapy for Squamous Cell Carcinoma of the Skin

Eighty-five squamous cell skin cancers treated with radiation therapy were reviewed, including 23 untreated primary tumors, 6 recurrent tumors, 16 synchronous or metachronous nodal metastases including 3 patients from the previous two groups, and 38 sites irradiated for microscopic residual cancer after surgery. The 5-year actuarial local controls were 0.54, 0.0, 0.42, and 0.79, respectively. No relationship between local control and either tumor size or radiation dose could be shown. Salvage treatment was attempted in 7 of 32 local failures, and has been successful in 4. Cancers arising in the settings of prior irradiation, renal transplant, hematopoietic malignancies, or chronic inflammation did not fare worse, and patients with parotid node metastases generally fared better with combined irradiation and surgery.Surgery followed by adjuvant irradiation confers a 5-year disease control probability of 0.79. Irradiation alone for untreated primary lesions, for recurrent primary lesions, or for untreated nodal metastases confers a disease control probability of ~0.50. Local or systemic predisposing factors do not confer an appreciably different prognosis. Parotid lymph node metastases are best served by combined modality treatment.

Felty's Syndrome: Effects of Splenectomy Upon Granulocyte Count and Granulocyte-Associated IgG

Clinical parameters and laboratory studies including granulocyte-associated IgG were documented in 15 patients with Feltys syndrome treated by splenectomy. Five patients did not benefit from splenectomy, six responded partially, and four completely. Response to splenectomy could not be predicted from age, sex, splenomegaly, preoperative granulocyte count, platelet count, lymphocyte count, bone marrow lymphocytosis, or granulocyte bound IgG. In contrast, marked elevation in preoperative serum granulocyte binding IgG predicted response to splenectomy. Furthermore, a postoperative fall in serum granulocyte binding IgG was associated with response. Thus, one beneficial effect of splenectomy in some Feltys syndrome patients is reduction of serum granulocyte binding immunoglobulin.

Low-dose radiation therapy for benign salivary disorders

Two patients, one with a persistent salivary fistula after surgery for a skin tumor overlying the parotid region, and the other with a ranula recurrent after surgery, were treated with low-dose irradiation. Both problems resolved after a total dose of less than 30 Gy, and neither patient experienced xerostomia. In selected patients, low-dose radiation therapy offers a solution to persistent salivary flow refractory to surgical management.

Effects of v-src Oncogene Activation on Radiation Sensitivity in Drug-Sensitive and in Multidrug-Resistant Rat Fibroblasts

Recent work has implicated the activated ras oncogene, whose gene product is a G-protein located in the plasma membrane, as well as the activated raf oncogene, whose gene product is a membrane-associated protein kinase, in contributing to radioresistance. Another transforming oncogene whose gene product is localized to the plasma membrane is v-src. We have examined a rat fibroblast line (RAT-1) infected with an avian sarcoma virus carrying a temperature-sensitive mutation in the v-src tyrosine kinase domain (LA-24). At 40 degrees C, LA-24 cells have a flat morphology and grow as a contact-inhibited monolayer, while at 35 degrees C, LA-24 cells have a transformed morphology, lose contact inhibition, grow in soft agar, and exhibit 3.5-fold higher tyrosine kinase activity. The parental RAT-1 line, not infected by the virus, grows at both temperatures as a contact-inhibited monolayer. This well-characterized system represents a good model for examining the effect of v-src transformation on radiosensitivity. RAT-1 and LA-24 cells grown at 35 and 40 degrees C were irradiated with graded doses of radiation, and clonogenic survival was assayed. For LA-24 cells grown at 35 and 40 degrees C, and for RAT-1 cells grown at 35 and 40 degrees C, calculated D0, n, alpha, and beta values did not differ significantly. To determine whether there might be differences in radiation damage repair capacity too subtle to detect by comparing radiation survival curves, sublethal damage repair capacity was assessed. There was no difference in sublethal damage repair capacity for LA-24 cells grown at 35 or 40 degrees C. Other studies have associated multidrug resistance with radioresistance. We have examined the radiation sensitivity of two colchicine-resistant LA-24 clones with four- to fivefold amplification of the P-glycoprotein gene, which are four-to fivefold more resistant to colchicine than the parental LA-24 line. In these multidrug-resistant clones, v-src activation does appear to increase radiation resistance. This did not appear to be due to alteration in cell cycle kinetics. We conclude that oncogene activation, or even protein kinase activity per se, does not necessarily lead to radiation resistance. Rather, radiation resistance following oncogene activation depends upon the oncogene and cell line studied, and perhaps upon specific protein phosphorylation.

Primary amyloidosis, pure red cell aplasia, and Kaposi's sarcoma in a single patient

A patient who developed primary amyloidosis, pure red cell aplasia, and Kaposis sarcoma is described. This is the second reported coincidence of Kaposis sarcoma and pure red cell aplasia and the first coincidence of Kaposis sarcoma and primary amyloid, thus enlarging the spectrum of plasma cell and immunoglobulin abnormalities seen in Kaposis sarcoma. Because immunelogic abnormalities have been described in all these diseases, it is felt that some primary immune dysfunction is the underlying cause of the three diseases in this patient.

Transient Monoclonal Immunoglobulin G with Anti-Dextran Activity

A patient with regional enteritis had received iron dextran for treatment of iron deficiency. Subsequently he developed a large (3.1 g/100 ml) IgG-K serum spike which had precipitin activity against dextran sulfate but not a variety of other antigens. There has been no evidence of multiple myeloma and the spike gradually disappeared spontaneously over the course of 2 years. We speculate that the monoclonal protein may have developed as a response to the iron dextran injections under the immunologic stress of a chronic inflammatory disease.

Analysis of survival in cancer clinical trials.

Excerpt The value of the randomized trial for the evaluation of new cancer therapies is undisputed. However, because such trials often do not accrue sufficient numbers of patients in a period of ti...

Tricyclic Antidepressants for Peripheral Neuropathy-Reply

In Reply.— We thank Drs Massey and Riley for their observations, particularly for their suggestion that tricyclic antidepressant drugs may alter pain in part by affecting peripheral nerve transmission. A controlled study of the effects of tricyclic antidepressants on pain, such as the one they are proposing, would be helpful, indeed.