Brenda Shank

A reappraisal of the role of prophylactic cranial irradiation in limited small cell lung cancer

The use of prophylactic cranial irradiation in limited stage small cell lung cancer remains controversial. Prospective trials have demonstrated that PCI can reduce central nervous system relapse rates, but the impact on survival remains questionable except for the possible evidence of a beneficial effect for long term survivors. With higher rates of thoracic control now obtainable with hyperfractionated radiation and concomitant chemotherapy, it becomes important to analyze the benefit of PCI in that setting. Before 1982, we included PCI in the management of all patients with limited stage small cell lung cancer; thereafter, we discontinued its use. This report compares the outcome of the two treatment approaches and addresses the role of PCI among patients who achieve durable local control. There were 36 limited stage small cell lung cancer patients treated with PCI from 1979-1982 and 26 patients treated without PCI from 1985-1989. Induction chemotherapy was followed in both groups by thoracic irradiation (45 Gy). The PCI patients received 30 Gy to the whole brain in 10 fractions. Both groups received maintenance chemotherapy. Of complete responders, brain failure was the first failure in 18% (4/22) of PCI (+) versus 45% (10/22) of PCI (-) (p = .04). Survival at 2 years was 42% for PCI (+) versus 13% for PCI (-) (p less than .05). When the analysis was limited to those patients permanently controlled in the thorax; there were 25% (4/16) brain failures PCI (+) versus 70% (7/10) PCI (-) (p = .03). For this same subset the 2-year survival was 56% PCI (+) versus 14% PCI (-) (p less than .05). There were no 5 year survivors without PCI compared to 38% (6/16) with PCI. These data suggest that PCI appears to be effective in enhancing survival of patients who achieve durable thoracic control. Prospective trials are necessary to evaluate the use of PCI combined with therapeutic regimens with a documented ability to achieve high rates of sustained control of thoracic disease.

Total body irradiation for marrow or stem-cell transplantation.

Although the best TBI-containing regimen may not yet have been found, data suggest that for greatest leukemic cell kill with minimum morbidity, a highly fractionated TBI regimen (10-13 fractions) to a high total dose (14-15 Gy) may be optimum. Bu-Cy may be able to replace TBI for CML, but results reported in the literature are still of an early nature. The addition of boost radiation has proven useful for treatment of the testes in leukemia patients, the spleen in some CML patients, and probably of the IF for lymphoma patients with residual or refractory disease. In the future, newer techniques, such as radiolabeled antibodies for better targeting of tumor cells, may prove useful and enter the therapeutic armamentarium (58).

Hyperfractionated total lymphoid irradiation and cyclophosphamide for preparation of previously transfused patients undergoing HLA-identical marrow transplantation for severe aplastic anemia

PURPOSE To assess the immunosuppressive capacity of hyperfractionated total lymphoid irradiation and cyclophosphamide for transplantation of unmodified allogeneic marrow in sensitized aplastic anemia patients. METHODS AND MATERIALS From February 1983 to September 1990, 23 multiply transfused aplastic anemia patients underwent unmodified bone marrow transplantation from HLA genotypically identical sibling donors following preparation with 6 Gy hyperfractionated total lymphoid irradiation and 160 mg/kg cyclophosphamide. Graft-versus-host disease prophylaxis included steroids in one patient, methotrexate in four, cyclosporine in seven, and methotrexate/cyclosporine in 12. There were 17 males and 6 females with a median age of 13 (range: 2.5-32). RESULTS One patient died early before engraftment of bacterial sepsis. Twenty-two patients were evaluable for engraftment. Three experienced graft failure including one primary, and two late graft failures associated with cyclosporine withdrawal. Acute graft-versus-host disease occurred in 7/22 (> or = grade II in 6), and chronic graft-versus-host disease in 3/17 patients. Except for a patient who received total body irradiation for a second transplant, no patient in this series developed interstitial pneumonia. Fifteen patients are alive with follow-up of 38-125 months (median 68). The overall actuarial survival at 5 years is 69%, at 8 years it is 60%, with one late death. The survival of adult patients was similar to that of younger patients (> or = 16 years old: 63%, < 16 years old: 55%). The development of acute graft-versus-host disease adversely influenced survival (88% with Grade 0-I, 17% with grade II-IV; p = 0.002). No hypothyroidism or secondary malignancies have been documented in this series. CONCLUSION Pretransplant immunosuppression with 6 Gy of hyperfractionated total lymphoid irradiation and 160 mg/kg CY reduces but does not eliminate the incidence of graft failure in sensitized aplastic anemia patients. The dose and the mode of administration of total lymphoid irradiation in this trial may be associated with a lower incidence of late side effects. Survival is comparable to that obtained using preparative regimens without radiation.

ATM heterozygosity and breast cancer: screening of 37 breast cancer patients for ATM mutations using a non-isotopic RNase cleavage-based assay

Based upon the results of several epidemiologic studies, it has been suggested that women who are carriers for a mutation in the ataxia telangiectasia-mutated (ATM) gene are susceptible for the development of breast cancer. Therefore, 37 consecutive breast cancer patients were screened for the presence of a germline ATM mutation using a non-isotopic RNase cleavage-based assay (NIRCA). This paper reports the first use of NIRCA for detection of ATM mutations in breast cancer patients. Using this assay, no ATM mutations were found in our patient population. This result is similar to the findings of other studies that have employed approaches complementary to NIRCA.

Nomograms for determining the probability of axillary node involvement in women with breast cancer

We have previously reported that a history of pregnancy is independently associated with axillary node involvement in breast cancer patients. We have now studied additional women with breast cancer and have used our data and the logistic model to produce nomograms for determining the risk of axillary node involvement, based on tumor size, age, and number of pregnancies. There was an increase in the incidence of axillary node involvement in women with a history of pregnancy. To exclude the confounding effect that tumor size or age might have on node involvement, logistic regression was performed. Pregnancy, tumor size, and age were the three independent variables. History of pregnancy had a significant effect on node involvement (P=0.036) that was independent of tumor size and age. Nomograms were constructed from these data. Surgeons do not perform an axillary dissection in every breast cancer patient. If the axilla is clinically negative and the tumor small, the surgeon, medical oncologist, and radiation oncologist may decide that a dissection need not be done. The nomograms in this article may allow for a more methodical choice of patients for axillary dissection. Moreover, a radiation oncologist might use the nomograms to help decide whether to irradiate an undissected axilla.

Is a fourth year necessary? the need for subspecialization: Total body irradiation

Although the number of radiation oncologists performing TBI procedures has increased in the last decade and there exists a significant body of unique medical knowledge pertinent to its use, there is little cohesiveness as a discipline within radiation oncology. There are no specific societies, journals, and no hospital divisions devoted to this area. Therefore, I content that subspecialty accreditation is not justified at this time. However, there are many fascinating scientific questions at the cellular, tissue, and clinical level which remain to be answered with regard to TBI, making it an exciting area for both laboratory and clinical research. Specialized training should be offered by institutions with expertise as a possible research year for residents and/or fellows who have a particular interest in pursuing an academic career along these lines.