The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy.

BACKGROUND: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal-lobular histology. METHODS: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and > or = 6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular features; these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. RESULTS: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and 13% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. CONCLUSIONS: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.

The significance of extracapsular extension of axillary lymph node metastases in early-stage breast cancer.

PURPOSE: To investigate if extracapsular extension (ECE) of axillary lymph node metastases predicts for a decreased rate of disease-free survival or an increased rate of regional recurrence of breast carcinoma. METHODS: The study population consisted of 368 patients with T1 or T2 breast cancer and pathologically-positive lymph nodes treated with breast-conserving therapy between 1968 and 1986. The median number of sampled lymph nodes was 10. Median follow-up time for the surviving patients was 139 months (range 70-244). Twenty percent of the patients were treated with supraclavicular RT, and 64% received both axillary and supraclavicular RT, with a median dose to the nodes of 45 Gy. The following factors were evaluated: presence of ECE, number of sampled lymph nodes (LN), number of involved LN, size of primary tumor, histologic grade of tumor, presence of lymphatic vessel invasion (LVI), presence of an extensive intraductal component (EIC), radiation dose, use of adjuvant chemotherapy, and age of patient. Recurrences were reported as the 5-year crude sites of first failure, and were divided into breast recurrences (LR), regional nodal failure (RNF, defined as isolated axillary, supraclavicular, or internal mammary recurrence), and distant metastases (DM). RESULTS: One hundred twenty-two patients (33%) had ECE and 246 patients did not. The median number of LN with ECE was 1 (range 1-10) and 20% of patients had ECE in > or =4 LN. Patients with ECE tended to be older (median age 51 vs. 47, p = 0.01), and had a higher number of involved LN (median 3 vs. 2, p = 0.005) than patients without ECE. Forty-three percent of patients with ECE had > or =4 involved LN compared to 15% of patients without ECE (p<0.0001). Models of ECE and the above factors revealed no significant correlation between ECE and either disease-free or overall survival. There was no statistically significant increase in local, regional nodal, or distant failures in patients with ECE as compared to patients without ECE. CONCLUSION: In this population of patients with nodal involvement, the presence of ECE correlates with the number of involved LN but does not appear to add predictive power to models of local, regional, or distant recurrence when the number of positive LN is included.

Impact of respiratory maneuvers on cardiac volume within left-breast radiation portals.

BACKGROUND: Late cardiac morbidity and mortality have been reported among left-breast cancer survivors treated with radiation therapy. Radiation-induced cardiotoxicity is affected by the volume of myocardium included in the radiation portals. We hypothesize that simple respiratory maneuvers may alter the position of the heart relative to the portals without altering the radiation dose delivered to the breast. METHODS AND RESULTS: Fourteen healthy female adult volunteers underwent cardiac MRI to determine the cardiac volume included in the typical left-breast radiation field during respiratory maneuvers. Cardiac volume within the radiation portals was assessed from a transverse stack of 14 1-cm-thick contiguous slices covering the entire heart, obtained during breath holding at end-tidal volume (baseline), deep inspiration, and forced expiration. Thirteen subjects (92%) had inclusion of a portion of the heart within the radiation portals at end-tidal volume (median, 20.9 cm3; range, 1.3 to 88.4 cm3). In these subjects, inspiration decreased the cardiac volume included within the radiation portals (median change: -10.7 cm3 [-40.2%], P<.001 versus end-tidal volume), whereas expiration increased the cardiac volume included (median change: 4.0 cm3 [21.5%]; P<.001 versus end-tidal volume). CONCLUSIONS: Inclusion of a portion of the heart in the left-breast radiation field is common. The use of simple inspiratory maneuvers significantly decreases cardiac volume within the radiation portals. Such an approach during delivery of radiation therapy may allow for preservation of radiation dosage to the breast while reducing cardiac involvement and subsequent mortality.

Design of an ultrasonic therapy system for breast cancer treatment.

This paper describes the design of a novel ultrasonic therapy system dedicated to the breast cancer treatment and the theoretical investigation of the heating characteristics of the system. The applicator is a cylinder comprised of a stack of rings. Each ring has up to 48 transducers mounted on the inside of the ring and directed towards the centre. The transducers operate in one of two frequency bands (1.8-2.8 MHz and 4.3-40.8 MHz), arranged alternately in each ring. During treatment the patient is positioned in prone position, with the breast immersed in water and surrounded by this array. This design was modelled and optimized by 3-D simulations for a variety of treatment conditions. The simulated results demonstrate that the system has an excellent capability to achieve and maintain a temperature distribution (41.5-44 degrees C) in a quadrant to a whole breast. Initial experiments using a single ring of transducers has been performed to verify the power deposition calculation.

Mammographically detected, clinically occult ductal carcinoma in situ treated with breast-conserving surgery and definitive breast irradiation.

PURPOSE: Ductal carcinoma in situ (DCIS) is increasingly detected as a nonpalpable lesion on mammographic screening performed for the early detection of breast cancer. Because of the growing incidence of mammographically detected DCIS, the present study was undertaken to determine the outcome of treatment of nonpalpable, mammographically detected intraductal carcinoma of the breast using breast-conserving surgery and definitive breast irradiation. MATERIALS AND METHODS: An analysis was performed of 110 women who presented with unilateral, nonpalpable, mammographically detected intraductal carcinoma of the breast and who were treated with breast-conserving surgery and definitive breast irradiation at 10 institutions in Europe and the United States. In all patients, complete gross excision of the primary tumor was performed, and breast irradiation was delivered with definitive intent. When performed, pathologic axillary lymph node staging was node negative (n=29). The median follow-up time was 9.3 years. RESULTS: The 10-year actuarial overall survival rate was 93%, and the 10-year actuarial cause-specific survival rate was 96%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 15 local recurrences in the treated breast. The actuarial rate of local failure was 7% at 5 years and 14% at 10 years. The histology of the local recurrence was intraductal carcinoma in 9 cases and invasive ductal carcinoma (with or without associated intraductal carcinoma) in 6 cases. The median time to local recurrence was 5.0 years (mean, 5.4; range, 2.1-15.2). With a median follow-up time of 4.4 years after salvage treatment, 14 of the 15 patients with local recurrence were alive without evidence of disease at the time of last follow-up examination. The crude incidence of local recurrence was 7% (3/42) when the final pathology margin of tumor excision was negative, 29% (5/17) when the margin was close or positive, and 14% (7/51) when the margin was unknown. There was no difference in the rate of local recurrence based on pathologic characteristics of the primary tumor. DISCUSSION: Results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases at 10 years following the treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Local recurrences within the treated breast were detected early and were treated with salvage for cure. These results support the initial treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Improvements in patient selection have the potential to reduce the risk of local recurrence.

Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast.

PURPOSE: To determine the 15-year outcome for women with ductal carcinoma in situ (DCIS, intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. PATIENTS AND METHODS: An analysis was performed of 270 intraductal breast carcinomas in 268 women from 10 institutions in Europe and the United States. In all patients, breast-conserving surgery included complete gross excision of the primary tumor followed by definitive breast irradiation. When performed, pathologic axillary lymph node staging was node-negative (n=86). The median follow-up time was 10.3 years (range, 0.9 to 26.8). RESULTS: The 15-year actuarial overall survival rate was 87%, and the 15-year actuarial cause-specific survival rate was 96%. The 15-year actuarial rate of freedom from distant metastases was 96%. There were 45 local recurrences in the treated breast, and the 15-year actuarial rate of local failure was 19%. The median time to local failure was 5.2 years (range, 1.4 to 16.8). A number of clinical and pathologic parameters were evaluated for correlation with local failure, and none were predictive for local failure (all P > or = .15). CONCLUSION: The results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of DCIS of the breast using breast-conserving surgery and definitive breast irradiation. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of DCIS of the breast.

Endocrine and cytotoxic therapies for the management of advanced local breast cancer. Current clinical investigation.

There is a need for more clinical investigation in advanced local breast cancer. Both chemotherapy and endocrine therapy improve disease-free and overall survival and are now a routine part of standard patient care. Dose-intensive chemotherapy should be reserved for younger patients in large, controlled clinical trials. For operable patients, adequate surgical therapy of the breast and axilla remains a standard of care and provides the most important piece of prognostic information (i.e., the number of involved axillary lymph nodes). Tamoxifen treatment of the estrogen receptor-positive postmenopausal patient remains the standard, although chemotherapy may add a further increment to disease-free survival.

Long-term outcome following breast-conserving surgery and radiation therapy.

PURPOSE: To examine the long-term pattern and frequency of recurrences after breast-conserving therapy and whether the outcome was influenced by the era of treatment. METHODS AND MATERIALS: From 1968 to 1986, 1870 patients with unilateral Stage I or II breast cancer were treated at the Joint Center for Radiation Therapy. Of these, 1628 underwent gross tumor excision and received a dose of > 60 Gy to the tumor bed and constituted the study population. Patients were classified as without evidence of disease, dead from other causes (DOC), or by their first site of recurrence. First sites of recurrent disease were categorized as distant/regional (DF/RNF) or local (LR). Local recurrence was defined as the detection of any invasive or in situ carcinoma occurring in the ipsilateral breast and was further categorized as: true recurrence (TR), marginal miss (MM), skin recurrence (S), or elsewhere in the breast (E). Median follow-up in survivors was 116 months. Eighty patients (4.9%) were lost to follow-up at 3-175 months. The population was divided into two time cohorts: 1968-1982 (n = 810), with a median follow-up time of 143 months, and 1983-1986 (n = 792), with a median follow-up time of 95 months. RESULTS: The overall crude rates of ipsilateral breast recurrence were 7.4 and 13.3% at 5 and 10 years, respectively. Crude rates at 5 and 10 years were 5.7 and 9.3% for TR/MM and were 0.9 and 2.8% for E recurrences, respectively. The annual incidence rates for all LR ranged from 0.5-2.4% and was relatively constant after the first year. The annual incidence rates for TR/MM ranged from 0.4 to 1.9%, whereas for E recurrences the range was 0.1-0.7%. The crude rates of DF/RNF were 16.6 and 23.1% at 5 and 10 years, respectively. The annual incidence rates for DF/RNF ranged from 1-5% over all years. Although the magnitude of the incidence was different, DF/RNF recurrence predominated in years 1-3 for both node-positive and node-negative patients. For the 1968-1982 and 1983-1986 cohorts, the 5-year crude rates of ipsilateral breast recurrence were 8.8 and 5.9%, respectively. CONCLUSIONS: Distant and regional nodal failures were the predominant form of recurrence. The annual incidence rate of LR was relatively constant over the first decade. True recurrence/marginal miss was the most frequent type of ipsilateral breast recurrence and was highest during years 2 through 7. The risk of a recurrence elsewhere in the breast increased with longer follow-up and was highest during years 8 through 10. The 5-year crude rate of ipsilateral breast recurrence appeared lower in the 1983-1986 patient cohort compared to the 1968-1982 patient cohort (8.8% vs. 5.9%), but the distributions of site of first failure did not differ significantly (p = 0.13). Any decrease in ipsilateral breast recurrence likely reflects improvements in mammographic and pathologic evaluation, patient selection, and the increased use of reexcision.

Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours.

Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43 degrees C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration x time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59%) and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47%. This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worth of study, especially since a positive interaction between these modalities is found in laboratory models.

Local recurrence after conservative surgery and radiation therapy for ductal carcinoma in situ: Possible importance of family history.

PURPOSE: The optimal treatment of ductal carcinoma in situ is controversial. Traditionally, women with this disease have been treated with mastectomy with excellent results, but recently the need for such extensive surgery has been questioned. Long-term data on the use of conservative surgery and radiation therapy for treatment are limited. A retrospective analysis was performed to assess treatment outcome and prognostic factors for patients with ductal carcinoma in situ treated with conservative surgery and radiotherapy. PATIENTS AND METHODS: From 1976 to 1990, 76 women with ductal carcinoma in situ were treated with conservative surgery followed by radiation therapy. The median age at diagnosis was 48 years. Seventeen patients had a positive family history of breast cancer in a first-degree (n=8) or second-degree (n=9) relative. Median follow-up interval was 74 months for the 71 survivors. In 54 patients, the carcinoma was detected by mammography alone; in 13 patients, by mammography and physical examination; and in 4 patients, by physical examination with a normal mammogram; and in 5 patients, by physical examination alone without mammography. Fifty patients had re-excision after initial biopsy. Final margins were positive in 11, close in 11, negative in 34, and unknown in 20. The median volume of excised tissue was 60 cm3. The axilla was surgically staged in 30 patients (39%) and all were negative. The whole breast was irradiated to a dose of 45 to 50 Gy in all patients. Seventy-two patients also received a boost to the primary site. The median total radiation dose to the primary site was 61 Gy (range, 46 to 71). RESULTS: Seven patients had a recurrence in the treated breast at 16, 18, 41, 63, 72, 83, and 104 months after treatment. The 5- and 10-year actuarial rates of local recurrence were 4% and 15%, respectively. Six of seven recurrences occurred in the vicinity of the original lesion. Four local recurrences were invasive, and three were ductal carcinoma in situ. Two patients developed a contralateral invasive carcinoma. The 5- and 10-year cause-specific survival rates were 100% and 96%, respectively. The 10-year actuarial rate of local recurrence was 25% in the group with a total excision volume less than 60 cm3, as compared with 0% in those with 60 cm3 or more excised (P=0.04). In patients with a positive family history, the 10-year actuarial rate of local recurrence was 37%, as compared with 9% in patients with a negative family history (P=0.008). Of the 17 patients with a positive family history, four developed either an ipsilateral or contralateral invasive breast cancer, whereas 1 of the 58 patients without a family history developed a subsequent invasive breast cancer (P=0.008). CONCLUSION: These results suggest that patients with ductal carcinoma in situ treated with conservative surgery and radiotherapy (including a boost to the primary site) appear to benefit from wide, rather than limited, resection. These results also suggest that family history may be an important prognostic factor for progression of disease.

Long-term results of post-operative radiation therapy following mastectomy with or without chemotherapy in stage I-III breast cancer.

PURPOSE: To determine the risk of local-regional failure following post-mastectomy radiotherapy and the incidence of complications associated with such treatment. METHODS AND MATERIALS: We retrospectively analyzed the results in 309 patients with Stage I-III invasive breast cancer treated with post-mastectomy radiation therapy between 1975 and 1985. The median radiotherapy dose was 45 Gy in 1.8 to 2.25 Gy fractions. One hundred forty-seven (48%) of the patients received adjuvant systemic chemotherapy with 115 (78%) of these receiving a CMF-based or doxorubicin-containing regimen. The median follow-up time of surviving patients was 130 months (range, 28 to 191 months) after mastectomy. RESULTS: Seventeen patients (6%) developed a local-regional failure at an interval of 4 to 87 months after radiotherapy. Moderate or severe complications related to radiotherapy and requiring treatment were uncommon. Symptomatic radiation pneumonitis occurred in four patients (1.3%), arm edema in 18 (5.8%), and brachial plexopathy in 2 (0.6%). CONCLUSION: We conclude that post-operative radiotherapy is a safe and effective means of reducing local-regional failure following mastectomy. The efficacy of post-mastectomy radiotherapy in improving survival should be addressed in new large randomized controlled studies.

Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma.

We retrospectively reviewed the response rate and the acute and long-term toxicity of combined treatment using radiation therapy, hyperthermia, and chemotherapy in 29 patients with locally or regionally recurrent or advanced adenocarcinoma of the breast who completed at least 4 of the 6 prescribed hyperthermia treatments as part of a Phase I-II trial. Thirty-nine separate hyperthermia treatment fields were evaluated. Cisplatin alone or cisplatin with etanidazole or bleomycin was delivered just prior to hyperthermia once weekly. Hyperthermia was delivered to a target minimum tumor temperature of 43 degrees C +/- 0.5 for 60 min. Following hyperthermia, a 400 cGy fraction of radiation was given. The radiation fraction size on other days was 200 cGy. Twenty-two fields had previously been irradiated and 17 fields had not. Prior chemotherapy had been given in 24 of 29 patients (83%) and hormonal therapy given in 21 (72%). The median follow-up time is 10 months; 16/29 patients (55%) have died of disease. The overall complete response rate for all fields was 53%. Response rate was not related to any clinical factor, radiation dose, microwave or ultrasound technique, type of chemotherapy, or tumor temperatures, but the number of patients in the study population was small. A statistically significant association between the likelihood of complications and the total radiation therapy dose (previous radiation and present radiation) was found. Persistent ulceration lasting greater than 1 month after completing treatment was seen in 67% of previously irradiated fields compared to 21% of fields that had not been previously treated (p = 0.015). Surgical wound repair was needed for 38% of fields with a history of prior irradiation versus 6% of those without prior treatment (p = 0.050). A statistically significant radiation therapy dose response was found for the likelihood of these complications. None of the hyperthermia temperature parameters studied correlated with an increased risk of complication. We conclude that the combination of radiation therapy, hyperthermia, and chemotherapy results in a high rate of complete response. However, in patients who have been treated with prior radiation therapy, this combination may be more locally toxic than treatment with hyperthermia and radiation therapy alone. The precise impact of chemotherapy on the therapeutic index of hyperthermia and radiation therapy remains to be determined in randomized clinical trials.

Ten-year results of breast-conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast.

An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10-year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow-up time was 78 months (range, 11 to 197 months). The 10-year actuarial overall survival rate was 94%, and the 10-year actuarial cause-specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10-year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty-four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow-up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node-positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow-up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow-up of patients after breast-conservation and definitive irradiation is required.

Results of treating ductal carcinoma in situ of the breast with conservative surgery and radiation therapy.

To determine the frequency, pattern, and time course of tumor recurrence in the breast, the outcome of 38 women with ductal carcinoma in situ (DCIS) treated with conservative surgery and radiation therapy between 1976 and 1985 was studied. Surgery typically consisted of local excision without evaluation of the microscopic margins of resection. The median radiation dose to the tumor site was 6400 cGy. With a median follow-up time of 81 months, eight patients (21%) have experienced a recurrence in the breast. The time course to recurrence was protracted in some cases, with failures occurring at 17, 27, 43, 63, 71, 83, 92, and 104 months. The 5-year and 8-year actuarial rates of tumor recurrence in the breast were 8% and 27%, respectively. Seven patients had a recurrence at or near the primary tumor site, four with invasive carcinoma, and one had an invasive recurrence at a site elsewhere in the breast. No clinical or pathologic factor was significantly associated with an increased risk of recurrence, but the number of patients in the study population was small. The authors reached the following conclusions for patients with DCIS treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation: (1) recurrence in the breast may be seen in at least one fifth of the patients; (2) recurrence typically occurs at or near the primary site; and (3) recurrence can occur long after treatment. Careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy.

Can simulation measurements be used to predict the irradiated lung volume in the tangential fields in patients treated for breast cancer?

A simple method of estimating the amount of lung irradiated in patients with breast cancer would be of use in minimizing lung complications. To determine whether simple measurements taken at the time of simulation can be used to predict the lung volume in the radiation field, we performed CT scans as part of treatment planning in 40 cases undergoing radiotherapy for breast cancer. Parameters measured from simulator films included: (a) the perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall at the center of the field (CLD); (b) the maximum perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall (MLD); and (c) the length of lung (L) as measured at the posterior tangential field edge on the simulator film. CT scans of the chest were performed with the patient in the treatment position with 1 cm slice intervals, covering lung apex to base. The ipsilateral total lung area and the lung area included within the treatment port were calculated for each CT scan slice, multiplied by the slice thickness, and then integrated over all CT scan slices to give the volumes. The best predictor of the percent of ipsilateral lung volume treated by the tangential fields was the CLD. Employing linear regression analysis, a coefficient of determination r2 = 0.799 was calculated between CLD and percent treated ipsilateral lung volume on CT scan. In comparison, the coefficients for the other parameters were r2 = 0.784 for the MLD, r2 = 0.071 for L, and r2 = 0.690 for CLD x L. A CLD of 1.5 cm predicted that about 6% of the ipsilateral lung would be included in the tangential field, a CLD of 2.5 cm about 16%, and a CLD of 3.5 cm about 26% of the ipsilateral lung, with a mean 90% prediction interval of +/- 7.1% of ipsilateral lung volume. We conclude that the CLD measured at the time of simulation provides a reasonable estimate of the percent of the ipsilateral lung treated by the tangential fields. This information may be of value in evaluating the likelihood of pulmonary complications from such treatment and in minimizing toxicity.