Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.

Adjuvant irradiation after mastectomy in women with one to three positive axillary nodes: then no; now yes.

The decision whether to offer women with one to three positive nodes postmastectomy radiation after adjuvant chemotherapy has been the subject of intense discussion since the publication of two major randomized prospective trials. Although radiotherapy after mastectomy was an established treatment for women with four or more positive axillary nodes, before these studies, existing data did not justify its use in patients with less extensive nodal involvement. Now with results from these studies showing improved survival after radiotherapy in all node-positive premenopausal and perimenopausal women, with perhaps its greatest benefit in women with one to three positive nodes, practice patterns are again shifting toward strong consideration of treatment in women with less tumor involvement. The arguments supporting this new treatment philosophy are presented.

Changes in photon dose distributions due to breast prostheses.

PURPOSE: Subcutaneous prosthetic implants had been routinely used for cosmetic augmentation and for tissue replacement following mastectomy over the last 15 years. The implants come in many forms as the gel filler material and surrounding shell material(s) vary significantly. METHODS AND MATERIALS: This study uses a thin window parallel-plate chamber and thermoluminescent dosimeters to quantify and dosimetric changes to surrounding breast tissue due to the presence of the prosthesis. A mammographic phantom was compared to four commercial prostheses, namely two silicon gel fillers within two different shells (silicon or silicon/polyurethane), a tri-glyceride within silicon and a bio-oncotic gel within silicon/polyurethane. The latter two implants were designed with a low-Z fill for diagnostic imaging benefits. RESULTS: Ion chamber results indicate no significant alteration of depth doses away from the implant with only minor canceling (parallel opposed) interface perturbations for all implants. In addition the physical changes to the irradiated prostheses were quantified by tonometry testing and qualified by color change. Each implant exhibited color change following 50 Gy, and the bio-oncotic gel became significantly less formable following irradiation, and even less formable 6 weeks postirradiation. CONCLUSION: The data indicates that prostheses do not affect the photon beam distribution, but radiation does affect the prostheses.

Locally advanced (noninflammatory) carcinoma of the breast: results and comparison of various treatment modalities.

From 1968-1987 237 women with Stage III, noninflammatory breast cancer were treated with various modalities. Ninety-three (39%) had Stage IIIA tumors, and 144 (61%) had Stage IIIB, noninflammatory tumors (AJC, 1983 staging). Median follow-up was 5.4 years (range 2 to 22 years). No patients were lost to follow-up. Thirty-five patients (15%) were treated with irradiation alone, 27 (11%) with irradiation and adjuvant systemic therapy, 80 (34%) with mastectomy and irradiation, and 95 (40%) with combined mastectomy, irradiation, and systemic therapy. Local/regional control by treatment at 5 and 10 years, respectively, was 31% and 31% for irradiation alone, 47% and 47% for irradiation and systemic therapy, 80% and 80% for irradiation and mastectomy, and 93% and 78% for irradiation, mastectomy, and systemic therapy (p less than .0001). Actuarial disease-free survival by treatment was 19% and 12% for irradiation alone, 25% and 18% for irradiation and systemic therapy, 34% and 20% for irradiation and mastectomy, and 41% and 31% for irradiation, mastectomy, and systemic therapy, at 5 and 10 years, respectively (p = .0001). Patients given systemic therapy and/or irradiation prior to mastectomy had a better local/regional control and DFS and actuarial survival, although not achieving statistical significance (p = 0.10). Of the triple modality group of patients, there were no chest wall failures with chest wall doses greater than 5040 cGy (p = 0.3). There were 40/237 (17%) grade 2 or greater treatment sequelae. The administration of chemotherapy significantly increased complications.

Radiotherapy and breast reconstruction: clinical results and dosimetry.

Immediate or delayed reconstruction using implants or autologous tissue transfer is increasingly offered to women undergoing mastectomy for breast cancer. Some patients require radiotherapy for prevention of local/regional relapse, and some for post-surgical local/regional recurrence. Others with augmented breasts may opt for conservative surgery and irradiation. At Washington University, 70 breast cancers were irradiated in 66 patients following mastectomy with reconstruction (N = 61) or wide local excision of an augmented breast (N = 5). Two patients elected to have a second reconstruction after an unsatisfactory initial result. Thus, 72 breasts were evaluated after radiotherapy for tumor control, complications, cosmesis, and patient satisfaction. Locoregional failure occurred in only five patients, one following adjuvant radiotherapy after mastectomy with reconstruction and four following radiotherapy for recurrent breast cancer within a reconstructed breast. Grade 2 or 3 complications occurred in 34 patients (51%). The complication rate was highest in autologous tissue transfer reconstructions. Cosmetic results were evaluated good/excellent in 49% by physicians and 67% by patients. Immediate reconstructions had fewer good/excellent physician evaluations (32%) compared with reconstructions performed at least 6 weeks after radiotherapy (55%). Transverse rectus abdominis flaps had the best cosmesis scores, followed by permanent silicone prostheses, tissue expanders, latissimus dorsi, and gluteal flaps. Only 48% of patients would choose to have the same reconstructive procedure again. Phantom interface dosimetry with a parallel plate chamber and TLD measurements was performed. Radiotherapy and reconstruction are not incompatible, but careful consideration of their relative timing and technique appear to be important in optimizing cosmesis while minimizing complications.

Brachytherapy or electron beam boost in conservation therapy of carcinoma of the breast: a nonrandomized comparison.

PURPOSE: The results of breast-conservation therapy using breast irradiation and a boost to the tumor excision site with either electron beam or interstitial 192Ir implant are reviewed. METHODS AND MATERIALS: A total of 701 patients with histologically confirmed Stage T1 and T2 carcinoma of the breast were treated with wide local tumor excision or quadrantectomy and breast irradiation. The breast was treated with tangential fields using 4 or 6 MV photons to deliver 48 to 50 Gy in 1.8 to 2 Gy daily dose, in five weekly fractions. In 80 patients the regional lymphatics were irradiated. In 342 patients with Stage T1 and 107 with Stage T2 tumors, boost to the primary tumor excision site was delivered with 9 MeV and, more frequently, with 12 MeV electrons. In 91 patients with Stage T1 and 38 patients with Stage T2 tumors an interstitial 192Ir implant was performed. Tumor control, disease-free survival, cosmesis, and morbidity of therapy are reviewed. Minimum follow-up is 4 years (median 5.6 years; maximum, 24 years). RESULTS: The overall local tumor recurrence rates were 5% in the T1 and 11% in the T2 tumor groups. There was no significant difference in the breast relapse rate in patients treated with either electron beam or interstitial 192Ir boost. Regional lymph node recurrences were 1% in patients with T1 and 5% with T2 tumors. Distant metastases were recorded in 5% of the T1 and 23% of the T2 groups. The 10-year actuarial disease-free survival rates were 87% for patients with T1 and 75% with T2 tumors. Disease-free survival was exactly the same in patients receiving either electron beam or interstitial 192Ir boost. Cosmesis was rated as excellent/good in 84% of patients with T1 tumors treated with electron beam and 81% of patients treated with interstitial implant, and 74 and 79% respectively, in patients with T2 tumors. CONCLUSIONS: Breast-conservation therapy is an effective treatment for patients with T1 and T2 carcinoma of the breast. There is no difference in local tumor control, disease-free survival, cosmesis, or morbidity in patients treated with either electron beam or interstitial 192Ir implant boost. Clinical trials in progress will further elucidate this controversial subject.

Inflammatory carcinoma of the breast: treatment results on 107 patients.

From 1958 to 1985, 107 patients with a clinical and/or histopathologic diagnosis of non-metastatic inflammatory breast cancer received radiotherapy as all or part of initial treatment. Therapy included definitive irradiation alone in 31 patients, irradiation with mastectomy in 16 patients, irradiation and combination chemotherapy in 23 patients, and irradiation with chemotherapy and surgery in 37 patients. Survivors have a median follow-up of 30 months. Overall median relapse-free survival (RFS) was 12 months (12% at 5 years). Local control and relapse-free survival were significantly improved for patients receiving surgery as part of initial treatment: 19% (10/52) of operated patients experienced locoregional failure vs. 70% (37/53) not operated (p less than 0.0001). The median overall actuarial survival was 24 months (17% at 5 years). Patients who received surgery showed improved survival (44 months vs. 18 months median; 37% vs. 7% at 5 years; p = 0.0004). Chemotherapy also was associated with improved relapse-free survival (18 months vs. 8 months median; 20% vs. 5% at 5 years; p = 0.02) and actuarial survival (32 months vs. 17 months median; 23% vs. 3% at 5 years; p less than 0.02). Patients treated with initial chemotherapy (usually 2-3 cycles of CAF), surgery, and postoperative irradiation followed by maintenance chemotherapy showed a 34 month median relapse-free survival (37% at 5 years RFS) and a 47 month median survival (48% at 5 years). Moderate to severe complications were seen in 25% of patients, the most frequent complication being fibrosis of the breast or chest wall. There were two fatalities secondary to Adriamycin-induced cardiomyopathy. This study suggests better local control, with fewer complications, when surgery and irradiation are combined with multiagent chemotherapy. Further prospective clinical trials are strongly recommended.

Breast conservation therapy for intraductal carcinoma of the breast.

PURPOSE: Between 1979 and 1987, 76 women with 77 ductal carcinomas in-situ of the breast were evaluated by The Radiation Oncology Center after breast conservation surgery. METHODS AND MATERIALS: Seventy breasts (91%) had tylectomy and irradiation and seven breasts (9%) had tylectomy alone. Median follow-up was 4.0 years, with a range of 2-10 years. Fifty patients (65%) had occult lesions discovered by mammography with a median mammographic size of 0.9 cm. The twenty-six patients with presenting symptoms had a median clinical tumor size of 1.95 cm. All patients had local excision of the primary tumor. Of 15 patients who had axillary dissections, one had nodal metastasis. Seventy breasts were irradiated. Seven patients refused radiotherapy. RESULTS: Overall 5-year actuarial survival was 99%; 5-year actuarial disease-free survival was 89%; the 5-year actuarial intramammary tumor control rate for irradiated patients was 93% vs. 57% for patients not irradiated (p < 0.001). Comedocarcinoma had a 5-year actuarial tumor control rate of 75%, 88% in the irradiated group as compared to 98% for all other histologic subtypes of ductal carcinoma in situ (p < 0.03). All six patients with local failure were successfully salvaged by further surgery. Multivariate analysis revealed significant factors in local control to be (a) radiotherapy, (b) comedocarcinoma histology, and (c) menopausal status. CONCLUSIONS: Although the number of patients treated is small, and follow-up time is limited, these early results support the contention that the treatment of ductal carcinoma in situ by excision and irradiation is an acceptable alternative to mastectomy. We urge caution in treating patients with the comedocarcinoma subtype and counsel these patients to have more treatment than excision alone.

A report of RTOG 8206: a phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases.

Hemibody irradiation (HBI) in a single exposure is an effective and safe technique for palliation of symptoms due to widespread bony metastases (RTOG 78-10). The present study (82-06) sought to explore the possibility that HBI added to local-field irradiation might delay the onset of metastases in the hemibody effected, as assessed by bone scans and X rays, and decrease the frequency of further treatment. The results of this clinical trial establish that 800 cGy of HBI is indeed causes micro-metastases to regress, perhaps completely. A total of 499 patients were randomized to receive either HBI or no further treatment following completion of standard palliative local field irradiation (300 cGy x 10) to the symptomatic site. Improvement was seen in time-to-disease progression at one year, 35% for local + HBI versus 46% on the local-only control arm. Time-to-new disease in the targeted hemibody was also improved. At one year, 50% of patients on the local + HBI arm showed new disease compared to 68% on the local-only arm. Furthermore, the median time-to-new disease within the targeted HBI area was 12.6 months for the local + HBI arm versus 6.3 months for patients in the local-only arm. Time-to-new treatment within the hemibody segment was also delayed. At one year, 76% of the local only group had been retreated versus 60% in the local + HBI arm. There were no fatalities and no radiation pneumonitis was seen in the local + HBI arm. Overall, the incidence of toxicities was low (5-15%). The occurrence of severe hematopoetic toxicities were significantly different in the local + HBI arm, but they were transitory. One life-threatening thrombocytopenia occurred, for a limited time, indicating excellent tolerance to HBI. This clinical trial demonstrates that HBI has the potential to be used to treat systemic and occult metastases, particularly if both halves of the body can be treated.

Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone.

Definitive therapy for Stage I adenocarcinoma of the endometrium consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pre- and/or post-operative radiotherapy (RT) is employed in selected patients with poor prognostic factors such as poorly differentiated tumors or deep myometrial invasion by tumor. The results are reported of RT alone in 69 patients with Stage I adenocarcinoma of the endometrium who presented with severe, acute, and chronic medical illnesses which prevented surgical management of their disease. Sixty-three patients (91.3%) were obese or hypertensive. Twenty-seven patients (39.1%) had diabetes mellitus, 16 (23.2%) had congestive heart failure, and the remaining patients had such conditions as stroke (17.4%), coronary artery disease (15.9%), and recent myocardial infarction (13.0%). The median age for this group of patients was 72.0 years compared to 60.0 years for a concurrent group of 304 patients with Stage I adenocarcinoma of the endometrium treated at our institution with combined surgery and RT. RT consisted of intracavitary insertions alone (11 patients), intracavitary plus low dose external beam therapy (9 patients), and intracavitary therapy plus high dose external beam therapy (49 patients, definitive RT). Younger patients and those with poorly differentiated disease were treated more aggressively. The 5- and 10-year overall survival for all patients was 76.8 and 33.3%, respectively. The 5- and 10-year disease-free survival was 88.1 and 82.4%, respectively. The 5-year overall and disease-free survival for the group of 49 patients treated with definitive RT was 85.4% and 88.7% with 15/49 (30.6%) having poorly differentiated tumors. For the definitive therapy group, the 5- and 10-year disease-free survival was 94.3, 92.3, and 78.0% for grades I, II, and III, respectively. Analysis of patterns of failure showed that none of the patients failed in the pelvis alone. Two out of 11 (18.2%) receiving intracavitary therapy alone and 3/49 (6.1%) receiving definitive RT failed in the pelvis with simultaneous distant metastasis (DM). Three patients in the definitive RT group failed with DM only. Severe complications occurred in 8 patients (16%), all of whom received definitive RT.

Definitive irradiation in carcinoma of the vagina: long-term evaluation of results.

A retrospective analysis of 165 patients with histologically confirmed carcinoma of the vagina is reported. Actuarial disease-free 10-year survival was: Stage 0 (16 patients)--94%, Stage I (50 patients)--75%, Stage IIA (49 patients)--55%, Stage IIB (26 patients)--43%, Stage III (16 patients)--32%, Stage IV (8 patients)--0%. All but one of the in situ lesions were controlled with intracavitary therapy. Of the patients with Stage I disease, 86% showed no evidence of vaginal or pelvic recurrence. Most of them received interstitial or intracavitary therapy or both; the addition of external beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) 61% of the tumors were controlled with a combination of brachytherapy and external beam irradiation. Ten of 16 Stage III tumors were controlled in the pelvis. Two of the patients with Stage IV disease had no recurrence in the pelvis with relatively high doses of irradiation. The total incidence of distant metastases was 16% in Stage I, 30.6% in Stage IIA, 46.1% in Stage IIB, 62% in Stage III, and 50% in Stage IV. The dose of irradiation delivered to the primary tumor or the parametrial extension was critical in achieving successful results. The incidence of grade 2-3 complications (12%) is correlated with the stage of the tumor and type of treatment given. More effective irradiation techniques including the optimization of dose distribution by judicious combination of external irradiation and interstitial brachytherapy will be necessary to enhance loco-regional tumor control. The high incidence of distant metastases underscores the need for earlier diagnosis and effective systemic cytotoxic agents if survival is to be significantly improved in these patients.

Isolated local-regional recurrence of breast cancer following mastectomy: radiotherapeutic management.

Two hundred twenty-four patients with their first, isolated local-regional recurrence of breast cancer were irradiated with curative intent. Patients who had previous chest wall or regional lymphatic irradiation were not included in the study. With a median follow-up of 46 months (range 24 to 241 months), the 5- and 10-year survival for the entire group were 43% and 26%, respectively. Overall, 57% of the patients were projected to be loco-regionally controlled at 5 years. The 5-year local-regional tumor control was best for patients with isolated chest wall recurrences (63%), intermediate for nodal recurrences (45%), and poor for concomitant chest wall and nodal recurrences (27%). In patients with solitary chest wall recurrences, large field radiotherapy encompassing the entire chest wall resulted in a 5- and 10-year freedom from chest wall re-recurrence of 75% and 63% in contrast to 36% and 18% with small field irradiation (p = 0.0001). For the group with recurrences completely excised, tumor control was adequate at all doses ranging from 4500 to 7000 cGy. For the recurrences less than 3 cm, 100% were controlled at doses greater than or equal to 6000 cGy versus 76% at lower doses. No dose response could be demonstrated for the larger lesions. The supraclavicular failure rate was 16% without elective radiotherapy versus 6% with elective radiotherapy (p = 0.0489). Prophylactic irradiation of the uninvolved chest wall decreased the subsequent re-recurrence rate (17% versus 27%), but the difference is not statistically significant (p = .32). The incidence of chest wall re-recurrence was 12% with doses greater than or equal to 5000 cGy compared to 27% with no elective radiotherapy, but again was not statistically significant (p = .20). Axillary and internal mammary failures were infrequent, regardless of prophylactic treatment. Although the majority of patients with local and/or regional recurrence of breast cancer will eventually develop distant metastases and succumb to their disease, a significant percentage will live 5 years. Therefore, aggressive radiotherapy should be used to provide optimal local-regional control.(ABSTRACT TRUNCATED AT 400 WORDS)

Tumor control in long-term survivors following superficial hyperthermia.

Sixty tumors with a minimum of 1-year follow-up were treated with radiation and superficial microwave hyperthermia (915 MHz). The overall local control rate was 50% (30/60). The most important factor in outcome was appropriateness of the hyperthermia applicator. Tumors covered by at least the 25% iso-SAR contour achieved 65% local control versus 21% local control with less than 25% SAR coverage (p less than 0.01). Several measures of adequate minimum monitored tumor temperature and duration were considered. The measure best correlated with outcome was best single session time at or above 43 degrees C (t43). If each monitored tumor catheter achieved t43 greater than or equal to 30 minutes in at least one session, then tumor control was significantly (p less than 0.01) improved (63% with Min t43 greater than or equal to 30 versus 25% with Min t43 less than 30). Although there was considerable overlap between tumors with SAR greater than or equal to 25% and those achieving Min t43 greater than or equal to 30, a statistically significant (p = 0.02) difference could be demonstrated between the group meeting both the SAR and the minimum tumor time/duration standards as opposed to those meeting only one standard. The actuarial local progression-free survival for tumors most likely to have had adequate hyperthermia (defined as SAR greater than or equal to 25% and Min t43 greater than or equal to 30) and all other tumors did not begin to separate significantly until 8 to 12 months after treatment. Implications for future randomized studies are discussed.

Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone.

A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation therapy and conservation surgery for primary and recurrent carcinoma of the vulva: report of 40 patients and a review of the literature.

Forty patients with histologically confirmed primary or recurrent vulvar carcinoma were treated with radiation therapy for loco-regional disease. Nineteen of the patients with primary tumors received postoperative radiotherapy (5000 cGy in 6 weeks). Fifteen of the 19 exhibited local tumor control. Five patients with Stage III or IV disease were managed with radiotherapy alone. Four had a complete response with two currently NED. Two patients who received preoperative radiotherapy with local excision are also currently free of disease. The 4-year NED survival for the study population is 100%, 28%, 50%, 0% and 10% for Stage I, II, III, IV and recurrent tumors respectively. The poor results obtained in Stage II tumors is likely due to selection criteria since four of seven patients developed distant metastases. Two of the 14 patients treated for recurrent disease remain NED after local excision of their tumors prior to irradiation. Even though the number of patients is small no dose response for subclinical disease could be found between 4500 and 7000 cGy. Treatment morbidity was acceptable with two patients developing severe long-term complications requiring surgical intervention.

Mini-colpostats in the treatment of carcinoma of the uterine cervix.

Between 1976 and 1982, 293 patients were treated for carcinoma of the uterine cervix at Washington University by definitive radiotherapy consisting of external beam therapy and two standard Fletcher-Suit applications (tandem plus vaginal colpostats). In ninety-nine patients (34%) mini-colpostats (MC) were used for one or both of their intracavitary insertions while 194 (66%) patients were treated twice with regular Fletcher-Suit colpostats (RC). The frequency of MC use was related to the age and parity of the patients. The distribution by stage of MC and RC groups was not significantly different. Pelvic failure in the MC group was similar to that of the RC group (21% vs 24%). Five-year disease-free survival was also similar between the two groups: 86% vs 80% Stage IB, 57% vs 61% Stage IIA, 47% vs 52% Stage IIB, and 27% vs 45% Stage III for MC and RC groups, respectively. The rate of major complications (grade 3) was 15% in the MC group and 8% in the RC group (p = 0.08). Careful phantom dosimetric studies in both types of colpostats and correlations of dose distributions at various points in the pelvis with frequency of rectal and bladder complications were carried out. The bladder and rectum received a 5-10% higher mean radiation dose (Gy) in the MC group than in the RC group despite lower overall exposure (milligram-hours). Thermoluminescent dosimetry in a polystyrene phantom demonstrates that approximately 10% higher doses are delivered to the bladder, rectum, and point A with an MC system as compared to an RC system, for constant exposure in mgh. Phantom measurements of a newer MC with bladder and rectal shielding demonstrate no influence on the bladder and rectal point dose at a source separation of 3 cm; midline points of the bladder and rectum are not within the full shadow of the shields even if the colpostats are flush with the tandem. Implications for therapy are discussed.

Combined hyperthermia and irradiation in the treatment of superficial tumors: results of a prospective randomized trial of hyperthermia fractionation (1/wk vs 2/wk).

From December 1984 to December 1989, 240 superficially located recurrent/metastatic malignant lesions (173 patients) were enrolled in a prospective randomized study of one versus two hyperthermia fractions per week. In the majority of patients, the dose of radiation therapy was less than 4000 cGy over 4 to 5 weeks. Stratification was by tumor size, site, and histology. The goal of the hyperthermia sessions were 42.5 degrees C for 45-60 min minimum intra-tumor measured temperature. Hyperthermia was given after radiation within 30-60 min. External applicators, both microwave (over 90% of treatments) and ultrasound, were used. Overall, complete response rate in 222 evaluable lesions was 56.3% (125/222) with a minimum follow-up of 6 months and a maximum follow-up of 52 months. The complete response rate for once a week versus twice a week hyperthermia group was 54.7% and 57.8%, respectively. The severe complication rate was 18% (41/222). There was no difference between the two treatment arms. Cox regression analyses were performed to study the prognostic significance of patient characteristics, tumor characteristics, and treatment parameters. Detailed analysis and results are presented.

Survival following locoregional recurrence of breast cancer: univariate and multivariate analysis.

Although prognostic variables for locoregional recurrence of breast cancer have been evaluated by univariate analysis, multifactorial analysis has not been previously performed. In the present study, survival following chest wall and/or regional lymphatic recurrence was determined in 230 patients with locoregionally recurrent breast cancer without evidence of distant metastases treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology and affiliated hospitals. Multifactorial analysis demonstrated that the site of recurrences correlated most strongly with overall survival (p = 0.001). The 5-year actuarial overall survival was 44-49% for patients with isolated chest wall, axillary, and internal mammary lymph node recurrence. Patients with either supraclavicular, multiple lymphatic, or concomitant chest wall and lymphatic recurrence had an 21-24% 5-year overall survival. The 5-year disease-free survival was 28-37% for patients with chest wall, axillary, or internal mammary recurrences compared to 4-13% for those with supraclavicular, chest wall and lymphatic, or those with multiple sites of lymphatic recurrence. Disease-free interval from mastectomy to recurrence was also found to be a significant prognostic factor for overall survival (p = 0.005). Fifty percent of patients with a disease-free interval of at least 2 years survived 5 years following locoregional relapse, compared to 35% for those with disease-free interval of less than 2 years. In the subset of patients with small chest wall recurrences (excised or less than 3 cm) and a disease-free interval of at least 2 years, the 5-year overall and disease-free survivals were 67% and 54%, respectively. These results suggest that subsets of patients with locoregional recurrence of breast cancer can survive for long periods of time. The conventional wisdom that chest wall and/or regional nodal recurrence following mastectomy uniformly confers a dismal prognosis is not necessarily true.

The influence of young age and positive family history of breast cancer on the prognosis of ductal carcinoma in situ treated by excision with or without radiation therapy or by mastectomy.

BACKGROUND: Several recent studies have investigated the influence of family history on the progression of DCIS patients treated by tylectomy and radiation therapy. Since three treatment strategies have been used for DCIS at our institution, we evaluated the influence of family history and young age on outcome by treatment method. METHODS: Between 1/1/82 and 12/31/92, 128 patients were treated for DCIS by mastectomy (n = 50, 39%), tylectomy alone (n = 43, 34%), and tylectomy with radiation therapy (n = 35, 27%). Median follow-up is 8.7 years. Thirty-nine patients had a positive family history of breast cancer; 26 in a mother, sister, or daughter (first-degree relative); and 26 in a grandmother, aunt, or cousin (second-degree relative). Thirteen patients had a positive family history in both first- and second-degree relatives. RESULTS: Six women developed a recurrence in the treated breast; all of these were initially treated with tylectomy alone. There were no recurrences in the mastectomy group or the tylectomy patients treated with postoperative radiation therapy. Patients with a positive family history had a 10.3% local recurrence rate (LRR), vs. a 2.3% LRR in patients with a negative family history (p = 0.05). Four of 44 patients (9.1%) 50 years of age or younger recurred, compared to two of 84 patients (2.4%) over the age of 50 (p = 0.10). Fifteen patients had both a positive family history and were 50 years of age or younger. Among these women, the recurrence rate was 20%. Women in this group treated by lesionectomy alone had a LRR of 38% (3 of 8). CONCLUSION: The most important determinant of outcome was the selection of treatment modality, with all of the recurrences occurring in the tylectomy alone group. In addition to treatment method, a positive family history significantly influenced LRR in patients treated by tylectomy, especially in women 50 years of age or younger. These results suggest that DCIS patients, particularly premenopausal women with a positive family history, benefit from treatment of the entire breast, and raise concerns about treating patients with a possible genetic susceptibility to breast cancer with tylectomy alone.

Factors influencing cosmetic results after conservation therapy for breast cancer.

PURPOSE: Host, tumor, and treatment-related factors influencing cosmetic outcome are analyzed for patients receiving breast conservation treatment. METHODS AND MATERIALS: Four-hundred and fifty-eight patients with evaluable records for cosmesis evaluation, a subset of 701 patients treated for invasive breast cancer with conservation technique between 1969 and 1990, were prospectively analyzed. In 243 patients, cosmetic evaluation was not adequately recorded. Cosmesis evaluation was carried out from 3.7 months to 22.3 years, median of 4.4 years. By pathologic stage, tumors were 62% T1N0, 14% T1N1, 15%, T2N0, and 9% T2N1. The majority of patients were treated with 4-6 MV photons. Cosmetic evaluation was rated by both patient and physician every 4-6 months. A logistic regression analysis was completed using a stepwise logistic regression. P-values of 0.05 or less were considered significant. Excellent cosmetic scores were used in all statistical analyses unless otherwise specified. RESULTS: At most recent follow-up, 87% of patients and 81% of physicians scored their cosmetic outcome as excellent or good. Eighty-two percent of physician and patient evaluations agreed with excellent-good vs. fair-poor rating categories. Analysis demonstrated a lower proportion of excellent cosmetic scores when related to patient age > 60 years (p = 0.001), postmenopausal status (p = 0.02), black race (p = 0.0034), and T2 tumor size (p = 0.05). Surgical factors of importance were: volume of resection > 100 cm3 (p = 0.0001), scar orientation compliance with the National Surgical Adjuvant Breast Project (NSABP) guidelines (p = 0.0034), and > 20 cm2 skin resected (p = 0.0452). Extent of axillary surgery did not significantly affect breast cosmesis. Radiation factors affecting cosmesis included treatment volume (tangential breast fields only vs. three or more fields) (p = 0.034), whole breast dose in excess of 50 Gy (p = 0.0243), and total dose to tumor site > 65 Gy (p = 0.06), as well as optimum dose distribution with compensating filters (p = 0.002). Daily fraction size of 1.8 Gy vs. 2.0 Gy, boost vs. no boost, type of boost (brachytherapy vs. electrons), total radiation dose, and use of bolus were not significant factors. Use of concomitant chemotherapy with irradiation impaired excellent cosmetic outcome (p = 0.02). Use of sequential chemotherapy or adjuvant tamoxifen did not appear to diminish excellent cosmetic outcomes (p = 0.31). Logistic regression for excellent cosmetic outcome analysis was completed for age, tumor size, menopausal status, race, type of surgery, volume of breast tissue resected, scar orientations, whole breast radiation dose, total radiation dose, number of radiation fields treated, and use of adjuvant chemotherapy. Significant independent factors for excellent cosmetic outcome were: volume of tissue resected (p = 0.0001), type of surgery (p = 0.0001), breast radiation dose (p = 0.005), race (p = 0.002), and age (p = 0.007). CONCLUSIONS: Satisfactory cosmesis was recorded in 81% of patients. Impaired cosmetic results are more likely with improper orientation of tylectomy and axillary incisions, larger volume of breast resection, radiation dose to the entire breast in excess of 50.0 Gy, and concurrent administration of chemotherapy. Careful selection of treatment procedures for specific patients/tumors and refinement in surgical/irradiation techniques will enhance the cosmetic results in breast conservation therapy.