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Methods: Between 1981-1995.87 patients with medically inoperable Tl-2NO nonsmall cell lung cancer (NSCLC) were treated with radiotherapy alone. Patient characteristics: median age 69 (46 94). male 74%. Tl = 35%. T2 = 65% (2 patients with bilateral lesions), median size 3 cm (1 8 cm), and 61% diagnosed by incidental chest x-ray (CXR) findings. patients with a median FBVl of 1.15 liters (0.39 2.63). pulmonary function data was available in 42

To the Editor. —Dr Cobleigh and colleagues 1 have done a fine job in reviewing the issues associated with the use of ERT in breast cancer survivors. Although the article is subtitled "A Time for Change," I looked in vain for a specific statement that the prescription of estrogens for women with a history of breast cancer and severe postmenopausal symptoms is justified. They clearly state that clinical trials are justified, but equally clearly the answers from such trials are at least 10 years away. Since one of the issues is medical-legal and since JAMA is an authoritative publication, I would ask Cobleigh and colleagues to indicate what they think is a reasonable position for clinicians to take until the definitive trials are available.

One hundred eighty women with clinical Stage I or II operable breast carcinoma were treated by radiotherapy following local tumor excision at Yale-New Haven Hospital through 1980. With a median follow-up time of 6.9 years, the actuarial 5-year overall and disease-free survival rates were 82% and 78%, respectively. The 5-year actuarial breast-recurrence-free survival rate was 92%. Several clinical-histopathologic features and treatment parameters were assessed for their significance as predictors of local breast failure or distant relapse. Cox lifetable regression analysis showed that patients with clinical Stage II carcinomas had significantly worse overall and relapse-free survival rates, but clinical stage alone had no effect on the rate of breast recurrence. Furthermore, a decrease in overall and disease-free survival was evident when necrosis was present in the tumor or when patients had an infiltrating lobular carcinoma. Breast recurrence-free survival was also influenced adversely by the presence of these two tumor features, especially when either tumor necrosis or infiltrating lobular carcinoma was found in conjunction with clinical Stage II lesions. Other histologic features such as grade, vascular invasion, perineural invasion, or the presence of an intraductal component of carcinoma did not affect outcome, nor did the treatment techniques employed appear to have a differential effect.

Avascular necrosis of bone developed in eight patients with advanced Hodgkin's disease who had been treated with combined modality therapy and were in complete remission from their disease. A ninth patient not on protocol but treated with the combined modality program also developed avascular necrosis. The cumulative incidence was 10% among long-term survivors. The etiology is unclear. Prolonged corticosteroid administration has been implicated but usually in much larger doses than the patients in this series received. The possible roles of the other chemotherapeutic agents for Hodgkin's disease, and radiation are discussed. Considerable disability resulted for almost all patients. Three of seven patients primarily with avascular necrosis of the femoral heads had bilateral hip replacements with surgery anticipated in four others. The two patients primarily with humeral head involvement have limited use of their arms. This condition must be added to the known possible serious consequences of combination chemotherapy for Hodgkin's disease. It is uncertain if the frequency of avascular necrosis is higher in patients treated with both radiation and chemotherapy compared with chemotherapy alone. Further studies are needed from other institutions to clarify the frequency and cause of this problem.

A reasonable alternative to mastectomy for women with early stage breast cancer is wide local excision of the lesion coupled with radical radiation therapy. The recurrence and longevity results with this method have been as good as, if not better, than standard mastectomy after 10 years' clinical experience in a limited number of patients. The physical and psychological impact of this therapy is more acceptable than mastectomy to the woman with breast cancer in its earliest stages.

A new treatment program for advanced Hodgkin's disease employing five-drug combination chemotherapy and low dose radiation to the sites of bulk disease (nodal or parenchymal) was designed in 1969. Eighty patients have now been treated, 60 of whom have achieved a complete remission. More significantly, only 5 of the 60 completed responders have relapsed with follow-up from 1-6 years. The cumulative survival at 5 years of patients entering complete remission is 92%. For those patients not sustaining a complete remission, it is 19% at 2 years. This program has resulted in substantially lower relapse rates than previously reported by other investigators, probably because of the administration of radiotherapy in the manner described. Hopefully, a significant number of these patients may be cured of their disease.

Between 1970 and 1983, 442 patients were treated for carcinoma of the prostate at our university medical center. Of the patients 319 underwent radical prostatectomy and 159 (50 per cent) had positive surgical margins and/or seminal vesicle involvement. Of these 159 patients 46 received postoperative irradiation and the actuarial survival was 96, 90 and 90 per cent at 5, 10 and 15 years, respectively. Among the remaining 113 patients who were treated with an operation alone the corresponding figures were 82, 62 and 21 per cent, respectively (p equals 0.02). Considering deaths only of cancer, the surgery only patients had a 15-year actuarial survival of 25 per cent compared to 90 per cent for those who underwent postoperative radiotherapy (p equals 0.07). Actuarial survival free of disease for the surgery plus postoperative irradiation group at 15 years was 40 per cent compared to 28 per cent for the surgery only group (p equals 0.34). Actuarial local control in the irradiated patients was 96 per cent at 15 years versus 32 per cent for the surgery only group (p equals 0.009). Actuarial survival free of distant disease at 15 years was 42 per cent in the irradiated versus 72 per cent in the nonirradiated groups (p equals 0.104). Severe complications attributable to radiation included 3 cases of radiation cystitis, 1 patient with urinary incontinence and leg edema in 9 per cent of the patients undergoing postoperative irradiation compared to 2 per cent of those treated with radical prostatectomy only. Postoperative irradiation appears to be indicated in patients with carcinoma of the prostate who undergo radical prostatectomy and who have positive margins and/or seminal vesicle involvement. Local control is markedly improved (p equals 0.009) and actuarial survival also is benefitted. There was a trend toward decreased deaths of cancer with postoperative irradiation that approached statistical significance. Postoperative irradiation did not improve survival rates free of disease and free of distant disease over those achieved with surgery alone. This finding suggests that while postoperative irradiation may not improve the ultimate cure rate by controlling local disease, early deaths of cancer are reduced resulting in a meaningful increase in survival for these patients.

In order to assess the significance of large mediastinal masses in patients with Hodgkin's disease, we analyzed all patients with pathological stage (PS) IA or IIA disease evaluated and treated at Yale between 1969 and 1978. There were 131 such patients treated initially with radical radiotherapy only, combination chemotherapy being reserved for those who failed radiation. Actuarial 5 and 10 year survivals were 95%. The presence of a mediastinal mass reglardless of size did not affect survival. Relapse-free survival was 77% at 5 years, 74% at 10 years in the entire group. Patients with any mediastinal involvement had a 65% relapse-free survival, 72% if the mass was 33%. These differences are suggestive of a greater tendency of such patients to fail radiotherapy but the differences were not statistically significant. Patients who did fail radiotherapy were for the most part successfully retreated with combined modality therapy (chemotherapy and radiation), accounting for the overall survival of 95%. Only 6 patients died of causes related to Hodgin's disease and 2 of these deaths were related to combined modality therapy complications. Because of the serious potential long term consequences of combined modality treatment, it should be used with great caution and on an individual basis only in PSIA and IIA patients.

Eighteen patients with Stage III or IV nodular poorly differentiated lymphocytic lymphoma (malignant lymphoma, infiltrative nodular type, with predominately small cleaved cells) were treated with intermittent high-dose oral chlorambucil (16 mg/m2 daily for five consecutive days each month) for one year. Complete clinical remissions occurred in 78% of these patients and partial remissions in another 17%. Complete remission usually occurred within three months of beginning therapy and with a medial follow-up of 35 months no patient has relapsed. Toxicity, usually hematologic and occurring late in therapy, has been mild, necessitating termination of therapy in only one patient. Review of recent therapy fails to demonstrate a definite long-term advantage of more aggressive treatment regimens. Intermittent high-dose chlorambucil should be further evaluated as therapy for nodular poorly differentiated lymphocytic lymphoma.

We retrospectively analyzed 114 patients with non-Hodgkin's lymphoma, clinical stages I and II, classified by the criteria of Rappaport and treated by radiotherapy alone. Of 84 patients classifiable, one-third were nodular and two-thirds diffuse lymphomas. Berkson-Gage actuarial and relapse-free survivals were determined for these two groups and for subgroups stratified by histology, stage, and by presence or absence of extranodal disease. Five year relapse-free and overall survivals were 83% and 100%, respectively, for the nodular group and 37% and 59% for the diffuse group. Extranodal involvement was less frequent in the nodular (19%) than in the diffuse (52%) group, where it was associated with Stage IE disease and increased relapse-free and actuarial survival. Histopathological subtype in the diffuse group (histiocytic versus combined lymphocytic poorly differentiated and mixed lymphocytic-histiocytic) did not influence survival. Extranodal involvement and stage I disease were associated with better survival in the diffuse histiocytic group. Successful radiotherapy for all stages of disease, all histologies, was not correlated with extended versus involved fields, and 89% of the relapses in the entire series were by wide dissemination.

Three off-axis dosimetric parameters were evaluted for identical mantle fields using the Varian 4 MV linear accelerator and a Picker C8M cobalt-60 unit. These parameters were dose distribution, skin dose and integral dose. Comparisons showed higher doses in all three categories with the 4 MV accelerator when the tumor dose is specified at the central axis midline. These results emphasize the importance of off-axis dosimetry with both machines.

Approximately 50 per cent of cancer patients will receive radiation treatment during the course of their illness. Similar benefits from palliative and curative treatments are seen in the elderly. Considerations for incorporating radiation treatment into the cancer management of older patients are discussed. The basis of and strategies for improved patient tolerance are reviewed.

From 1969 to 1977, 124 patients with advanced staged Hodgkin's disease were entered into a treatment protocol which consisted of three cycles of drugs (nitrogen mustard, vincristine, vinblastine, prednisone, and procarbazine) followed by radiation (1500-2000 rad) to previous sites of known disease. After completion of radiation therapy, two more drug cycles were given. There were 63 newly diagnosed patients with Stage IIIB and IVA or B disease and 61 patients who had relapsed from prior radiotherapy. The median follow-up is now in excess of 5 years. Of the relapsed patients, 86.9% entered a complete remission and 90.6% of these patients have remained in complete remission from 1 to 10 years. In comparison, 81% of the newly diagnosed patients entered a complete remission and 78.4% of these patients continue free of disease from 1 to 11 years. These differences were not statistically significant. The 10-year actuarial disease-free survival--79.8% for the 61 relapsed patients compared to 65.6% for the 63 newly diagnosed patients--was not significantly different either. The 10-year actuarial survival for the 40 patients who had relapsed to IIIB and IVA or B was 71.3% and approximated more closely those of newly diagnosed IIIB and IVA or B patients. This drug-radiotherapy protocol is very effective for the treatment of patients who have relapsed from previous radiotherapy.

A treatment program for early stage breast cancer consisting of biopsy only and primary radiation therapy is described. The treatment plan is "radical" with tumoricidal doses or radiation delivered to the breast and axillary, supraclavicular, and internal mammory lymph nodes, i.e. 6000-7000 rads to clinically involved areas and 4500-5000 rads to subclinical disease. Thirty patients have been treated with this program, with followupranging from 1-10 years. Only 1 patient has died from her disease; 1 has had a lot oflocal recurrence readily controlled with mastectomy. Twenty-six patients arealive and well; there have been 3 deaths from intercurrent illness. No significant radiation complications have occurred. Radiation therapy as the sole treatment for breast cancer has been described in the literature for at least 20 years but generally ignored byclinicians. It deserves evaluation as a treatment option in randomized therapeutic trails.

The authors report three patients who developed fatal respiratory failure after limited or unilateral thoracic radiation therapy for neoplasms. The respiratory failure was characteristic of the adult respiratory distress syndrome (ARDS) with refractory hypoxemia and diffuse bilateral infiltrates including areas of lung well outside of the radiation ports. No patient received drugs known to cause lung injury, and cardiogenic edema and infections were excluded. At autopsy the lungs exhibited interstitial fibrosis, Type II alveolar cell hyperplasia, inflammatory infiltrates, and squamous metaplasia. The etiology of the pulmonary injury is unclear.

This report describes 150 patients with clinical stage I and II carcinoma of the breast treated at four institutions--Yale University School of Medicine, Harvard Medical School-Joint Center for Radiation Therapy, Hahnemann Medical College, Jefferson Medical College--with radiotherapy only following excisional biopsy. Closely similar treatment policies were followed at all four centers, 4500-5000 rads minimum tumor dose being delivered to the entire breast and axillary, supraclavicular and internal mammary nodes. Forty-six of 49 stage I patients treated are alive without disease, the actuarial relapse-free survival being 91% at 5 years. Of the 101 stage II patients, 75 are alive without disease with a relapse-free actuarial survival of 60% at 5 years. Local failure has occurred in 10 patients (9 stage II and 1 stage I, 6.6%) 5 of whom are disease-free following mastectomy. The results obtained in this study are comparable to those of conventional surgery. It is our conclusion that mastectomy is not a necessary part of the treatment of small breast cancers, that radiation without mastectomy is an acceptable alternative with far superior cosmetic and functional results. Adjuvant chemotherapy should be considered particularly in stage II patients in view of their 40% relapse rate.

Eighteen patients with osseous involvement were identified from a series of 124 consecutive patients treated with combined-modality therapy with advanced-stage or relapsing Hodgkin's disease. Multiple lesions were seen as frequently as were solitary lesions. Nodular sclerosing histology was as prevalent as mixed cellularity disease. However, those five cases initially diagnosed at protocol entry were predominantly mixed cellularity (80%) with multiple lesions (80%). Sites of involvement included: the spine, 24; pelvis, 8; ribs, 4; femur, 3; skull, 1; and shoulder 1. Actuarial survival for these patients was 84% at nine years. Only three patients were induction failures and no patient has had a relapse. Patients with bone lesions had favorable responses to combined-modality therapy.

A new program for treating advanced Hodgkin's disease (mostly stage IIIB and IV) employs five drugs and low dose radiotherapy. Three cycles of nitrogen mustard, vincristine, procarbazine, vinblastine and prednisone are given over six months, followed by 1,500–2,500 rads to all diseased areas. Following radiotherapy, two additional cycles of chemotherapy are given. Of 34 patients in this program, 25 have completed three cycles (six months) of drug treatment plus irradiation. Twenty of the 25 are in complete remission, continually free of disease, with a median duration of 12+ months. The principal toxic manifestation of the program is bone marrow depression.

During the years 1958-1969, 123 patients with Stage I, II and IIIA Hodgkin's disease were treated with radical radiation therapy in the Department of Radiation Therapy at the Yale-New Haven Hospital. The cumulative survival of Stage I and II patients was 72 per cent at 5 years counting all patients and 54 per cent including only those patients living and free of disease. Reactivations of disease occurred in 50 per cent of patients and were associated with a poor prognosis. Ninety per cent of patients who relapsed are either living with disease or dead.In order to improve the staging accuracy and subsequent therapy, exploratory laparotomy was begun in January 1969. Forty untreated, newly diagnosed patients have undergone this procedure in 1969 and 1970. Of 26 patients with Stage I and II disease by all criteria except surgery, 7 proved to have abdominal disease following surgery. In addition, a high degree of splenic involvement that was unsuspected clinically has been found. These results suggest that Hod...

The treatment of Hodgkin’s disease is a complicated affair with many guidelines for management of a variety of clinical presentations but also considerable controversy regarding the treatment of different subsets. Perhaps the most controversy surrounds the management of “intermediate” stages of Hodgkin’s disease, IIIA and IIB. The former is a subject of a report by Dr. Powlis and his colleagues in this issue of the Int. J. Radiat. Oncol. Biol. Phys. Before addressing some of the issues raised by that report, it is well to remember that Hodgkin’s disease is an uncommon disorder with an estimated 7,300 new cases for the United States in 1 98718 (compared with 130,900 for breast carcinoma, for example) and that Stage IIIA is an uncommon subset, comprising about 15% of all Hodgkin’s disease.’ When one starts to ask questions about the management of subsets of IIIA disease, it is evident that the answers will not be forthcoming from prospective randomized trials and that any answer from retrospective data analysis is likely to be incomplete. With that introduction, let’s examine the Powlis report from the Joint Center for Radiation Therapy at Harvard and the University of Pennsylvania with respect to how it agrees with prior studies, how it differs, and what the reasons for the differences might be. We will also try to establish some unifying principles from the data to guide the clinician who, in the last analysis, has to make some hard decisions and may have difficulty putting the patient in precisely the right pigeonhole. Powlis et al. have looked specifically at the subset of III, Hodgkin’s disease patients which they have labelled “minimal” IIIA disease and examined the impact of three different kinds of treatment, combined modality therapy (CMT), total nodal irradiation (TNI), and mantle and para-aortic irradiation (MPA). It is evident from the paper that the three groups are not entirely comparable with respect to the patients receiving these treatments and that the MPG group is a more favorable one in several respects, and additionally has been followed for considerably less time than the other two groups. Nevertheless, the CMT group has the best results with all 22 patients alive and only 1 relapse. Result with TN1 or MPA are very similar to one another with about half of the patients relapsing in each group and about 80% of patients alive in each group. About 90% of the III1 patients had splenic involvement and the authors examined the influence of the number of splenic nodules on outcome, as suggested by Hoppe et d7 Patients getting CMT all did very well no matter what the number of splenic nodules. With TN1 patients with greater than 5 splenic nodules relapsed considerably more often than those with less than 5; furthermore, patients with nodular sclerosis/lymphocyte predominant histologies seemed to do better than those with mixed cellularity or lymphocyte depletion disease. For patients treated with MPA irradiation, the number of splenic nodules did not appear to matter, but the histology of the disease did. The authors concluded that: 1. Within the group of III1 patients, only the subset of patients with less than 5 splenic nodules and with nodular sclerosing/lymphocyte predominant histology were suitable for radiation therapy alone. 2. That MPA irradiation was as good as TNI. 3. All other IIIA patients should be treated with combined modality therapy.

• Twenty-two patients with inflammatory breast carcinoma received preoperative chemotherapy consisting of weekly administration of cyclophosphamide, doxorubicin hydrochloride, fluorouracil, and vincristine sulfate for six weeks. Postoperative therapy consisted of 22 weeks of biweekly administration of these drugs. Regional radiotherapeutic consolidation followed chemotherapy. Nineteen patients completed therapy. Twelve of these patients remain disease free (median, 15 months; range, four to 32 months). Median disease-free survival for all 22 patients is 13 months or more (range, zero to 32 months). Median overall survival is 18 months or more (range, one to 33 months). This regimen compares favorably with prolonged adjuvant and maintenance chemotherapy for inflammatory breast carcinoma. ( Arch Surg 1987;122:1329-1332)

From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.

The treatment of Hodgkin’s disease has become a very successful and satisfying endeavor for both the radiation oncologist and medical oncologist. Cure rates of 90–95% may be achieved for the patient with pathologic stages I and II disease [1, 2, 3]. For patients with more advanced stages, chemotherapy alone or, as our data suggest, preferably in combination with radiation, will succeed in curing 65–75% of patients [4, 5]. This chapter, however, will not discuss in any detail the therapy of advanced disease. Our purpose is to evaluate the role of combination chemotherapy either alone or with radiation in the management of more limited stage disease.

As part of an ongoing Phase II trial at Duke University Medical Center (DUMC), patients with Stage IIB-IVA soft tissue sarcomas (STS) potentially amenable to wide local excision were treated with preoperative hyperthermia (HT) plus radiation therapy (RT), with HT randomized to one versus two treatments per week, stratified with respect to tumor volume. 17 patients were treated and analyzed. HT was given 30-60 minutes after RT, with heating maintained for 1 hour after 42.0 degrees C was reached. In patients treated with 2 HT per week, treatments were separated by 48 hrs. Concurrent RT was given with 180-200 cGy fractions, five treatments per week, to a nominal tumor dose of 5000-5040 cGy. Surgical extirpation was performed 4 weeks after completion of HT/RT. Treatment effect was evaluated by histopathologic examination of the resected lesions, according to a previously reported system. The mean number of HT given in the 1 and 2/wk groups was 4.4 and 7.3, respectively (p less than 0.01). Tmax for the 1 and 2 HT/wk groups was 42.4 +/- 2.1 degrees C and 43.5 +/- 1.8 degrees C, and T min was 38.1 +/- 0.8 degrees C and 38.6 +/- 0.5 degrees C, respectively. The increase in T min from first to last treatment was 0.5 +/- 1.2 degrees C and 1.0 +/- 0.8 degrees C, respectively. The T min from the best treatment was 39.1 +/- 1.2 degrees C and 40.0 +/- 1.0 degrees C, and the Tmax from the best treatment was 44.5 +/- 3.4 degrees C and 45.4 +/- 2.5 degrees C for the 1 and 2 HT/wk groups, respectively. There were no statistically significant differences between the 2 treatment groups for any of the above temperature parameters. Severe histopathologic changes were found in 71% (12 of 17) of the lesions. T min and Tmax and highest T min and Tmax were between 0.4-1.1 degrees C higher in patients with severe changes (p = NS). All 9 patients in the 2 HT/wk group had extensive changes, versus only 3 of the 8 patients in the 1 HT/wk group. This difference was highly statistically significant (p = 0.009, two-tailed Fisher's exact test). These findings suggest an advantage to twice weekly, as opposed to weekly, HT in the setting of this study. Whether there is a corresponding therapeutic gain, or whether these results can be extrapolated to other settings requires further investigational efforts. It is recommended that treatment parameters, particularly temperature parameters, continue to be examined in Phase II trials.

We have analyzed a series of 48 patients with Hodgkin's disease who were pathologically Staged IIIA and treated with total nodal irradiation alone. The cumulative overall survival is 80% at 5 years; the cumulative relapse-free survival, however, is only 35% at 5 years. When the patients are subdivided into clinical Stage (CS) I, II/pathological Stage (PS) III and CS III/PS III categories, the relapse-free 5 year cumulative survivals are 50% and 15%, respectively. Patients less than 20 years of age had a 5 year relapse-free survival of 65% vs 28% for those over 20. These results, particularly in terms of freedom from relapse, are not as good as those being obtained in more advanced disease with the use of both combination chemotherapy plus irradiation. Combined modality therapy with both drugs and irradiation appears indicated for most Stage MA patients.

The combination of radiation therapy and multiple agent chemotherapy is becoming increasingly popular, particularly in the management of Hodgkin’s disease and other lymphomas, but also in a wide variety of malignancies-childhood cancers, carcinoma of the ovary, testicular carcinoma, to name a few. The evidence is increasing, however, that such combined modality treatment has to be carried out with considerable caution to avoid untoward effects on normal tissues. The subject recently has been reviewed extensively by Phillips and Fu.’ Radiation injury may be enhanced by a variety of cancer chemotherapeutic agents; however, the worst offenders appear to be the antineoplastic antiiiotics, particularly actinomycin D and adriamycin. Such enhancement may occur whether drugs are given before, concurrently, or after radiotherapy. It is impossible to predict on theoretic grounds the extent to which radiation injury may be augmented by specific drugs, but a variety of animal and clinical data show an increase in the dose effect from 10 to 80% in normal tissues. When the normal tissues in question are vital ones such as the heart, lungs and intestine the radiotherapist should be especially cautious. Wara and Phillips have suggested, for example, a maximum whole lung does of 1500 rad (g-10 fractions) when chemotherapeutic drugs have been or will be used, as opposed to 2500 rad when no drug therapy is contemplated.’ In addition the combination of drugs and radiation appears to increase considerably the risk of a second malignancy.’ Unfortunately, little data are available concerning the enhancement of radiation effect on human tumors by antineoplastic agents. Whether or not the therapeutic ratio is altered favorably remains to be seen. In the present issue of this Journal Kun et al. present additional evidence for the enhancement of normal tissue radiation injnry by chemotherapeutic agents. In a small series of patients with Stage IIB and IIIB Hodgkin’s disease, MOPPt chemotherapy followed by full dose radiotherapy resulted in serious radiation injury, including 4 deaths, in 15 of 28 patients. There were 5 patients who developed radiation pneumonitis, 2 with pericarditis, 2 with severe intestinal injuries (one of whom had a transverse myelitis also), 3 patients with excessive subcutaneous fibrosis, 2 patients with disseminated herpes xoster (one of whom subsequently developed acute leukemia as well) and one patient with a bronchoesophageal fistula. This contrasted with 2 patients with radiation pneumonitis (both of whom had massive mediastinal disease) and no other serious complications in 55 patients who were treated with radiation alone at the same institution. Apart from the risks involved in the treatment of Hodgkin’s disease with full doses of both chemotherapy and radiation, conventional doses of radiation probably are not necessary. Since the demonstration 10 years ago that approximately 4OOOrad in 4 weeks’ time was required to produce 95% local control,3 radiotherapists have given this amount in most instauoes when they were treating a patient with Hodgkin’s disease, no matter what the stage. In advanced Hodgkin’s

This report describes a detailed analysis of the dosimetry of the mantle technique for the therapy of Hodgkin's disease when a 4 MV linear accelerator (Varian) is utilized. Doses were determined in a Rando phantom and in vivo using several methods of dosimetry. Significant dose variations, exacerbated by the lead flattening filter, were found. For peripheral doses, where the nodes are near the surface (e.g., neck and axillae), increases of 20-30% were the rule. To adjust for these substantial differences, a shrinking field technique was adopted, obviating the need for complex compensating systems. The doses for the inverted Y field were relatively uniform.

Cancer of the breast remains the most common form of cancer in women in the United States, with an estimated 100,000 new cases and 34,000 deaths in 1979. It is also undoubtedly the most controversial malignancy in terms of its manage­ment. Historically, attempts to improve the cure rate of this disease have focused on different approaches to local therapy, such as performing a more extensive operation or adding radiation to inaccessible lymph nodes. These attempts have been based on the notion that breast cancer begins as a single focus and spreads in an orderly fashion to regional lymph nodes before it disseminates to distant sites.

With the large Patterns of Care study, however, there appears to be a small frequency of intestinal obstruction secondary to infradiaphragmatic radiotherapy in patients who never had a laparotomy. Other reports in the literature suggest the frequency of small bowel obstruction is greater in patients who had radiotherapy and surgery than in those who had surgery alone.” Additionally small bowel obstruction is a well recognized event and probably the most frequent complication of pelvic radiotherapy for a variety of malignancies, so one might predict an increased frequency in patients having both staging laparotomy and radiotherapy. The frequency of 3% major bowel problems in the Patterns of Care study does not seem very large but even that figure may be more than is necessary. The authors question the necessity for doses greater than 35 Gy in patients with Hodgkin’s disease and seminoma and we would like to further elaborate on this point. Since the majority of patients with seminoma have Stage I disease, the usual problem presented to the radiotherapist is the prophylactic therapy of abdominal nodes or treatment of subclinical disease. The necessity for such treatment is currently being questioned, since it is estimated that only about 10 to 20% of Stage I patients will actually have occult disease in abdominal lymph nodes.’

Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969–1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III 2 received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach.

Fluosol-DA 20% (Fluosol) is an emulsion of perfluorodecalin and perfluorotripropylamine, which has the ability to carry oxygen and has been shown to enhance the ability of radiation to control tumors in animal studies. Since November 1984, patients with unresectable squamous cell carcinomas of the head and neck have been enrolled in a study to evaluate the safety and potential efficacy of this adjuvant therapy. Forty-six patients were entered of which 37 completed radiation and are evaluable. Patients were infused weekly with Fluosol and then breathed 100% oxygen for a minimum of 30 minutes prior to and during radiation. Eleven patients received 5 infusions of 8 mL/Kg, four patients 6 infusions of 8 mL/Kg, five patients 5 infusions of 9 mL/Kg, seven patients 7 infusions of 7 mL/Kg and eight patients 8 infusions of 7 mL/Kg. Nine patients had Stage III disease, 20 patients Stage IV disease and 8 patients had failed previous therapy with chemotherapy and/or surgery. The radiation doses delivered ranged from 6600 cGy to 7500 cGy. The overall complete response rate for this group was 76%. All 9 Stage III patients were complete responders, 13 of 20 Stage IV responded and 6 of 8 with previous therapy were complete responders. The survival rate at 1 year was 67% for absolute and 78% as determinant. Of those patients achieving a complete response, 75% continued free of disease 1 year after therapy. Out of 254 total test doses, 11 patients experienced a reaction to the test dose of Fluosol. Of 235 total infusions 6 patients experienced a reaction during the Fluosol infusion with 7 patients experiencing post infusion reactions. These were readily controlled with diphenhydramine or acetominophen. Elevated liver enzymes were observed in some patients with a mean time to normalization of 102 days for alkaline phosphatase, 39 days for SGOT, and 46 days for SGPT.