Breast-conserving surgery and radiotherapy for early breast cancer

Breast conservation is not a commonly prescribed treatment option for breast cancer in Taiwan. We report 42 patients with 43 early-stage breast cancers who were treated with breast-conserving surgery and radiotherapy at the Koo Foundation Sun Yat-Sen Cancer Center from April 1990 to December 1994. Included in this study were 33 patients with stage I cancers and 10 with stage II. Breast-conserving surgery consisted of wide local excision and ipsilateral axillary lymph node dissection. Radiotherapy was given 2 to 6 weeks after surgery, with a dose of 46 to 50 Gy, 2 Gy per fraction per day, to the whole breast, and an additional 14 to 18 Gy to the original tumor site. Irradiation to the regional lymph nodes was not performed in patients with negative axillary lymph nodes. Sixteen out of 43 (37%) patients were treated with adjuvant chemotherapy. The local control rate 3 years after treatment was 97% and relapse-free survival was 91%. The cosmetic outcome in 41 treated breasts that were rendered relapse-free by conserving treatment were evaluated and graded by the physicians as excellent, good, fair or poor using a standardized scale. Forty breasts (98%) were scored as excellent or good for their cosmetic results. Breast-conserving surgery and radio-therapy offer Taiwanese women with early breast cancer excellent local control and a highly satisfactory cosmetic outcome.     

Adjuvant radiation after conservative surgery for early breast cancer. Local control and cosmetic outcome

Between 1980 and 1987, 115 patients with early breast cancer underwent conservative surgery and radiation therapy. Median follow-up from the date of surgery was 48 months. There was local recurrence in 5 of the 115 patients. Of this group, 67 patients were evaluable for cosmetic outcome. The overall cosmetic result was judged by a panel to be excellent or good in 61%, fair in 27%, and poor in 12%. Patients themselves found the cosmetic result to be excellent or good in 94%. Retraction of the inferior border of the breast, surface difference between both breasts, breast induration, scar retraction and telangiectasia correlated with the cosmetic score. Type of surgery, axillary irradiation, use of bolus, and length of follow-up all influenced the cosmetic outcome in a univariate analysis.     

Generation of superoxide anion and induction of superoxide dismutase and peroxidase in bean leaves infected with pathogenic fungi

PURPOSE: The purpose of this study was to review management strategies with respect to systemic therapy, radiation therapy treatment techniques, and patient outcome (local regional control, distant metastases, and overall survival) in patients undergoing conservative surgery and radiation therapy (CS + RT) who had four or more lymph nodes involved at the time of original diagnosis. METHODS AND MATERIALS: Of 1040 patients undergoing CS + RT at our institution prior to December 1989, 579 patients underwent axillary lymph node dissection. Of those patients undergoing axillary lymph node dissection, 167 had positive nodes and 51 of these patients had four or more positive lymph nodes involved and serve as the patient population base for this study. All patients received radiation therapy to the intact breast using tangential fields with subsequent electron beam boost to the tumor bed to a total median dose of 64 Gy. The majority of patients received regional nodal irradiation as follows: 40 patients received RT to the supraclavicular region without axilla to a median dose of 46 Gy, 10 patients received radiation to the supraclavicular region and axilla to a median dose of 46 Gy. Thirty of the 51 patients received a separate internal mammary port with a mixed beam of photons and electrons. One patient received radiation to the tangents alone without regional nodal irradiation. Adjuvant systemic therapy was used in 49 of the 51 patients (96%) with 27 patients receiving chemotherapy alone, 14 patients receiving cytotoxic chemotherapy and tamoxifen, and 8 patients receiving tamoxifen alone. RESULTS: As of December 1994, with a minimum evaluable follow-up of 5 years and a median follow-up of 9.29 years, there have been 18 distant relapses, 2 nodal relapses, and 5 breast relapses. Actuarial statistics reveal a 10-year distant metastases-free rate of 65%, 10-year nodal recurrence-free rate of 96%, and a 10-year breast recurrence-free rate of 82%. All five patients who sustained a breast relapse were successfully salvaged with mastectomy. Both patients with nodal relapses (one supraclavicular and one axillary/supraclavicular) failed within the irradiated volume. Of the 40 patients treated to the supraclavicular fossa (omitting complete axillary radiation), none failed in the dissected axilla. With a median follow-up of nearly 10 years, 29 of the 51 patients (57%) remain alive without evidence of disease, 15 (29%) have died with disease, 2 (4%) remain alive with disease, and 5 (10%) have died without evidence of disease. Overall actuarial 10-year survival for these 51 patients is 58%. CONCLUSIONS: We conclude that in patients found to have four or more positive lymph nodes at the time of axillary lymph node dissection, conservative surgery followed by radiation therapy to the intact breast with appropriate adjuvant systemic therapy results in a reasonable long-term survival with a high rate of local regional control. Omission of axillary radiation in this subset of patients appears appropriate because there were no axillary failures among the 41 dissected but unirradiated axillae.     

Silicon analysis of breast and capsular tissue from patients with saline or silicone gel breast implants: II. Correlation with connective-tissue disease

The silicone breast implant controversy rages on. Recent work has demonstrated that normal or baseline breast tissue silicon levels in women who had had no prior exposure to any type of breast implant may be as high as 446 microg/gm of tissue. These data ranged from 4 to 446 microg/gm of tissue, with a median of 27.0 microg/gm of tissue. In addition, numerous other epidemiologic and rheumatologic studies have demonstrated no association between silicone breast implants and any connective-tissue diseases. Despite these reports, the use of silicone implants remains restricted. The present study measured breast and capsular tissue silicon levels from 23 breasts in 14 patients with saline implants, and from 42 breasts in 29 patients with silicone implants. No patient in the saline implant group presented with signs or symptoms of connective-tissue disease. Patients with silicone implants, however, were divided into three groups based on the presence or absence of signs or symptoms of connective-tissue disease: group I, no symptoms or signs; group II, + symptoms, no signs; and group III, + symptoms, + signs. Six patients in group III were diagnosed with a specific connective-tissue disease, including systemic lupus erythematosus, rheumatoid arthritis, or scleroderma. The most common indications for implant removal or exchange were capsular contracture and implant rupture, although 41 percent of patients with silicone implants expressed media-related concern over the implant issue. The most common symptoms described by patients in groups II and III were joint pain and stiffness, arm pain and numbness, and fatigue. In all groups, capsular tissue silicon levels were significantly greater than breast tissue levels. This finding may indicate that the capsule serves as a barrier to the distribution of silicone from the implant into adjacent breast tissue. Although breast tissue silicon levels in patients with silicone implants were not significantly greater than those in patients with saline implants (p = 0.48), capsular tissue levels in patients with silicone implants were, indeed, significantly greater than those in patients with saline implants (p < 0.001). However, no statistically significant differences in tissue silicon levels were observed with relation to the presence or absence of connective-tissue disease signs or symptoms in patients with silicone implants (groups I to III). Therefore, these data strengthen the conclusion that there is no association between tissue silicon levels and connective-tissue disease.     

The effects of postradiation treatment with tamoxifen on local control and cosmetic outcome in the conservatively treated breast

BACKGROUND: The aim of this study was to evaluate the impact on disease recurrence and cosmetic outcome of tamoxifen treatment initiated after breast-conserving therapy (BCT). METHODS: Between 1982 and 1994, 498 women (509 breasts) were treated with BCT in accordance with a highly standardized institutional protocol. Adjuvant tamoxifen was administered to 130 patients (134 breasts), beginning 1-6 weeks after irradiation. The median ages and duration of follow-up for groups who received tamoxifen (TAM+) and no tamoxifen (TAM-) were 62.5 years/56 months and 53 years/60 months, respectively. The members of the TAM+ group were significantly older (P = 0.0001) and had increased incidences of positive axillary lymph nodes or undissected axilla (P = 0.001). There was a significant (P = 0.001) difference between the TAM+ and TAM- groups in the distribution of histopathologic subtypes; this reflected an increased proportion of associated ductal carcinoma in situ in the TAM- group. More extensive regional lymphatic irradiation was administered to the TAM+ group. Chemotherapy was administered to 15% of TAM+ and 28% (P = 0.003) of TAM- patients. There were no significant differences between the groups with respect to tumor size, reexcision, total excised tissue volume, final margin status, total radiation dose, or use of interstitial implant boost. RESULTS: There was no significant difference between the TAM+ and TAM- groups in the overall distribution of cosmetic scores (P = 0.18). The 5-, 7-, and 10-year actuarial local failure rates for TAM+ versus TAM- patients were 0% versus 3.1%, 1.9% versus 5.4%, and 1.9% versus 8.4%, respectively. Multivariate regression analyses of potentially confounding variables revealed no significant associations between tamoxifen and either cosmetic outcome or local failure. CONCLUSIONS: Radiotherapy followed by tamoxifen has no adverse interactive effect on cosmesis, and tamoxifen is associated with a trend toward enhanced 5-year local control probability.     

Total versus partial musculofascial coverage for steroid-containing double-lumen breast implants in augmentation mammaplasty

The use of intraluminal steroids in double-lumen breast implants is effective in preventing fibrous capsular contraction around the implant. This technique has not been accepted widely, however, and remains controversial primarily because steroid-related complications, including extrusion, late inferior migration, and atrophy of the skin, have been associated with their use. This nonrandomized retrospective study of 76 patients (146 breasts) who underwent submuscular augmentation of the breast through inframammary and periareolar incisions compares results after total musculofascial coverage of the implant with partial muscle coverage of the implant. In patients with partial muscle coverage of the implant, 7.8% steroid-related complications were observed. In the group with total musculofascial coverage of the implant, no steroid-related complications and no symptomatic contractions of the capsule were observed. Our study suggests that total musculofascial coverage provides a statistically significant margin of protection from steroid-related complications compared with techniques using only partial muscle coverage of the implant in patients who underwent cosmetic augmentation mammaplasty.     

Early-stage bilateral breast cancer treated with breast-conserving surgery and definitive irradiation: the University of Pennsylvania experience

PURPOSE: To determine whether patients with early-stage bilateral breast cancer can be treated with definitive irradiation following breast-conserving surgery with acceptable survival, local control, complications, and cosmesis. METHODS AND MATERIALS: During the period 1977-1992, 55 women with Stage 0, I, or II concurrent (n = 12) or sequential (n = 43) bilateral breast cancer were treated with definitive irradiation following breast-conserving surgery. The records of these 55 patients with 110 treated breasts were reviewed for tumor size, histology, pathologic axillary lymph node status, first and overall site(s) of failure, and adjuvant chemotherapy or hormonal therapy. Curves for survival, local control, and regional control were determined. Cosmetic outcome, complication rates, and matching technique were analyzed. The median total radiation dose delivered was 64 Gy (range 42-72) using tangential whole-breast irradiation followed by an electron or iridium implant boost. The tangential fields were matched with no overlap in 40 patients (73%); there was overlap on skin of up to 4 cm in 14 patients (25%); and the matching technique was unknown in 1 patient (2%). The median follow-up for the 12 women with concurrent bilateral breast cancer was 4.0 years. The median follow-up for the other 43 women with sequential cancer was 9.3 and 4.9 years, respectively, after the first and second cancers. RESULTS: For the overall group of 55 patients, the 5- and 10-year overall survival rates were 96% and 94%, respectively, after treatment of the first cancer, and 96% and 92%, respectively, after treatment of the second cancer. The 5- and 10-year actuarial relapse-free survival rates were 90% and 75%, respectively, after treatment of the first cancer, and 83% and 72%, respectively, after treatment of the second cancer. For the 110 treated breast cancers, the 5- and 10-year actuarial local failure rates were 5% and 15%, respectively. Complication rates were: 28% breast edema, 8% arm edema, 4% pneumonitis, 3% cellulitis, 1% rib fracture, and 1% brachial plexopathy; no patient developed matchline fibrosis. For patients with a minimum of 3 years of relapse-free follow-up, the rate of excellent or good cosmetic outcome for 104 treated breasts was 85%. CONCLUSION: Definitive irradiation after breast-conserving surgery is technically feasible for selected patients with concurrent or sequential early-stage bilateral breast cancer. Survival, local control, complication rates, and cosmetic outcomes appear comparable to historical reports of breast conservation treatment for unilateral disease. Bilateral definitive breast irradiation after breast-conservation surgery should be considered an acceptable alternative treatment to bilateral mastectomy for selected patients with concurrent or sequential early-stage bilateral breast cancer.     

The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.     

Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients

PURPOSE: To assess the cardiac effects of two different cumulative doses of adjuvant doxorubicin and radiation therapy (RT) in breast cancer patients. PATIENTS AND METHODS: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyclophosphamide (500 mg/ m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4). RESULTS: The estimated risk (95% confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than for CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P=.02]. The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose-volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. CONCLUSION: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose-volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.     

Human basophil activation measured by CD63 expression and LTC4 release in IgE-mediated food allergy

BACKGROUNDS AND OBJECTIVES: We present the interim findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast conserving therapy (BCT). METHODS: From 1 March 1993 through 1 January 1995, 50 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation alone using an interstitial LDR implant. Patients were eligible if their tumor was an infiltrating ductal carcinoma < or =3 cm in diameter, surgical margins were clear by at least 2 mm, the tumor did not contain an extensive intraductal component, the axilla was surgically staged with < or =3 nodes involved with cancer, and a postoperative mammogram was performed. Implants were positioned using a template guide delivering 50 Gy over 96 hr to the lumpectomy bed plus a 1-2-cm margin. Local control, cosmetic outcome, and complications were assessed. RESULTS: Patients ranged in age from 40 to 84 years (median, 65). The median tumor size was 10 mm (range, 1-25). Seventeen of 50 patients (34%) had well-differentiated tumors, 22 (44%) had moderately differentiated tumors, and in 11 (22%) the tumor was poorly differentiated. Forty-five patients (90%) were node-negative while five (10%) had 1-3 positive nodes. A total of 23 (46%) patients were placed on tamoxifen and 3 (6%) received adjuvant systemic chemotherapy. No patient was lost to follow-up. The median follow-up for surviving patients is 47 months (range, 37-59). No patient has experienced a local, regional, or distant failure. Three patients have died at 19, 33, and 39 months after treatment. All were without clinical evidence of recurrent disease and all deaths were unrelated to treatment. Good-to-excellent cosmetic results have been observed in 49 of 50 patients (98%) (median cosmetic follow-up was 44 months with a range of 19-59). No patient has experienced significant sequelae related to their implant. CONCLUSIONS: Interim results with treatment of the tumor bed alone with an LDR interstitial implant appear promising. Long-term follow-up of these patients and additional studies will be necessary to establish the equivalence of this treatment approach compared to standard BCT.     

A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer

PURPOSE: To evaluate the efficacy and safety of docetaxel in patients with paclitaxel-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Docetaxel (100 mg/m2) was administered every 3 weeks to 46 patients registered at four centers. Patients had previously received < or = two chemotherapy regimens for MBC. All patients had progressive disease while receiving paclitaxel therapy. Treatment was repeated until there was evidence of disease progression or for a maximum of three cycles after best response. RESULTS: Objective responses were seen in eight of 44 assessable patients (18.1%; 95% confidence interval [CI], 6.7% to 29.5%). Seven patients had partial responses and one patient responded completely. Response rates were not significantly different by previously received paclitaxel dose or resistance. No responses were seen in 12 patients who had previously received paclitaxel by 24-hour infusion, but the response rate in 32 patients who had received paclitaxel by 1- to 3-hour infusion was 25%. The median response duration was 29 weeks and the median time to disease progression was 10 weeks. Median survival was 10.5 months. Clinically significant (severe) adverse events included neutropenic fever (24% of patients), asthenia (22%), infection (13%), stomatitis (9%), neurosensory changes (7%), myalgia (7%), and diarrhea (7%). CONCLUSION: Docetaxel is active in patients with paclitaxel-resistant breast cancer, particularly in those who failed to respond to brief infusions of paclitaxel. Response rates were comparable to or better than those seen with other therapies for patients with paclitaxel-resistant MBC. This confirms preclinical studies, which indicated only partial cross-resistance between paclitaxel and docetaxel.     

Nipple-sparing total mastectomy of large breasts: the role of tissue expansion

Nipple-sparing total mastectomy remains an alternative for management of patients with high risk breast disease or patients with various types of symptomatic breast problems. In a patient with large breasts, however, achieving good cosmesis while still performing a thorough mastectomy remains a challenge. This report includes 10 patients who underwent unilateral nipple-sparing total mastectomy and 10 patients who underwent bilateral nipple-sparing total mastectomy. Tissue expansion was used as the reconstructive technique in this consecutive series done from 1985 through 1988. All expanders were placed in the submuscular position, and hyperbaric oxygen was used when intraoperative fluorescein administration identified marginally perfused areas. The average volume of breast tissue removed was 800 gm. The average permanent implant size was 767 cc. Complications included partial skin or nipple loss, infection, and problems related to the implants themselves. The complication rate, however, was not excessive, and results have been good as measured by cosmetic results, capsule grade, and lack of development of cancer in operated breasts. This reconstructive technique is recommended as an alternative in those patients undergoing nipple-sparing total mastectomy.     

Aesthetic outcome of breast implant removal in 85 consecutive patients

As we began to see increasing numbers of women concerned about their gel-filled breast implants, we became aware that we could not advise them with any degree of confidence what they might expect in terms of aesthetic result after implant removal. We decided to review the records and outcomes over a 2-year period of a number of patients who underwent implant removal. Eighty-five consecutive patients were reviewed, 69 of whom had undergone cosmetic augmentation and 16 of whom had breast reconstruction with silicone gel implant(s). Thirty-nine of the 69 cosmetic augmentation patients had removal of implants alone, and 27 had removal accompanied by mastopexy. Three had reaugmentation with saline-filled implants; one had replacement with saline-filled implants. Fifteen of the 16 reconstruction patients underwent autogenous tissue transfer. Preoperative and postoperative photographs of all patients were mixed randomly and rated by two independent raters in four aesthetic categories on a five-point scoring system. Repeatability was measured several weeks later, when each rater scored randomly selected photographs from this patient pool. The patients also performed their own outcome evaluations by means of questionnaire. We discovered that cosmetic augmentation patients who undergo implant removal only often suffer adverse aesthetic results. The postremoval appearance of many cosmetic augmentation patients actually will be improved over their preoperative appearance when mastopexy is performed in conjunction with implant removal. The study demonstrated that patients with certain body types could expect a particular outcome; i.e., women with asthenic builds and older patients with lax, striated breast skin generally had unsatisfactory aesthetic outcomes with implant removal only. Patients selected for autogenous breast reconstruction had favorable results, with extended latissimus dorsi and TRAM flaps yielding equally good outcomes. The study allows us to offer patients an optimistic view of postoperative results following breast implant removal. We have begun to advise selected patients that implant removal accompanied by mastopexy provides a more pleasing aesthetic outcome than implant removal alone.     

Autologous breast reconstruction after breast-conserving cancer surgery

Breast-conserving therapy, which aims to reduce trauma by preserving as much of a patient's natural appearance as possible, does not necessarily lead to an optimal cosmesis. We hypothesized that combining plastic and oncologic surgeries would greatly reduce the physical and psychological traumas and produce an optimal cosmesis without impairing the oncologic outcome. We performed breast reconstruction on 40 cancer patients. Of those 40 patients, 15 received combined plastic and oncologic surgeries. Procedures depended on breast size: mammareduction plasty in cases with sufficient volume, and reconstruction using myocutaneous latissimus dorsi flaps for those with less volume. Cosmetic results were rated good to poor. Of the 15 primary reconstruction patients, 86.7 percent of the cases showed good results and 13.3 percent fair; in the secondary cases, 68 percent were good, 16 percent fair, and 16 percent poor. Through a follow-up and cosmetic evaluations by both surgeons and patients, the study showed that combining aesthetic improvements and oncologic surgery does not compromise patient safety, reduces mental and physical trauma, and frequently results in superior cosmesis, thereby improving the patient's overall health.     

A note on the possibility of explaining why a color cannot be both red and green

OBJECTIVE: This study was a blinded, concurrent assessment of a historical cohort derived from a provincial registry (1978 to 1986) of breast implant recipients (cosmetic, not reconstructive) and controls (other cosmetic surgery) to test the hypothesis that connective tissue disease (CTD) is increased in breast implant recipients. METHODS: Women who underwent breast implant or other cosmetic surgery during the interval from 1978 to 1986 were contacted confidentially by Alberta Health and asked to participate in the study. Those willing to participate completed an extensive questionnaire and supplied a blood sample, subsequent to which all surgical records were reviewed to confirm implant type(s) or cosmetic surgery(ies). All participants with any suggestion of rheumatic disease were assessed blindly by a rheumatologist for CTD. RESULTS: One thousand five hundred seventy-six breast implant recipients were recruited, including 1112 who had received silicone gel-filled implants (> 13,500 person yrs exposure). Seven hundred twenty-six controls were recruited. Prevalence rates adjusted for sex and age for rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and Sj?gren's syndrome (the principal targeted conditions) were consistent with published reports for Caucasian women. While breast implant recipients self-reported significantly greater rates of symptoms than controls, post-surgical diagnoses of the principal targeted conditions did not indicate an increased incidence of typical or atypical CTD. CONCLUSION: The results of the study do not support the hypothesis that silicone gel-filled implants induce or promote CTD.     

Direction of predator approach and the decision to flee to a refuge

PURPOSE: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. METHODS AND MATERIALS: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. RESULTS: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). CONCLUSION: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.     

Paclitaxel with mitoxantrone, fluorouracil, and high-dose leucovorin in the treatment of metastatic breast cancer: a phase II trial

PURPOSE: Paclitaxel is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. In this phase II study, we added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin (NFL). PATIENTS AND METHODS: Forty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous (i.v.) infusion on day 1, mitoxantrone 10 mg/m2 by i.v. bolus on day 1, 5-FU 350 mg2/m by i.v. bolus on days 1, 2, and 3, and leucovorin 300 mg i.v. over 30 to 60 minutes immediately preceding 5-FU on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients. RESULTS: Twenty-three of 45 assessable patients (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. Hospitalization for treatment of fever during neutropenia was required in 13% of courses, and two patients died as a result of sepsis. Two patients developed severe congestive heart failure after a large cumulative anthracycline dose. CONCLUSION: This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although its activity compared with other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than anticipated based on previous results with the NFL regimen or with paclitaxel administered at this dose and schedule as a single agent. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with the paclitaxel/doxorubicin combination.     

Adjuvant systemic chemotherapy and hormonal therapy. Effect on local recurrence in the conservatively treated breast cancer patient

BACKGROUND: The purpose of this study is to determine the impact of adjuvant systemic chemotherapy and adjuvant hormonal therapy on local relapse in the conservatively treated breast. MATERIALS AND METHODS: Before December 1989, 548 patients underwent lumpectomy with axillary dissection followed by radiation therapy to the intact breast. Adjuvant systemic therapy was administered as clinically indicated. The majority of patients with pathologically involved lymph nodes received adjuvant systemic therapy, whereas those with pathologically negative lymph nodes received no adjuvant systemic therapy. The majority of patients received a course of radiation therapy either concomitant with or before systemic therapy. In only nine cases was radiation therapy delayed more than 16 weeks after surgery. RESULTS: As of June 1992, the 548 patients had a median follow-up of 6.4 years. In univariate and multivariate Cox regression analysis, patient age and adjuvant systemic chemotherapy were statistically significant independent prognostic factors relating to breast relapse. Those patients who received adjuvant systemic chemotherapy had a lower breast relapse than those who did not. Among patients who received tamoxifen, there was a statistically insignificant trend toward a lower relapse rate compared with those who did not receive tamoxifen. CONCLUSIONS: It appears from this retrospective analysis that patients who received adjuvant systemic therapy, either concomitantly or after their course of radiation therapy, had a lower relapse rate in the conservatively treated breast than those patients who received no adjuvant systemic therapy.     

Mixed mesodermal tumor of the ovary. Description of a case with a small primary neoplastic mass. Anatomo-clinical and histogenetic considerations]

Forty-one patients with locally advanced hypopharyngeal carcinomas were followed for at least 3 years (median, 60 months) after simultaneous radiochemotherapy. Conventionally fractionated radiotherapy was administered as 5 x 2 Gy/week to a total dose of 30 Gy within 3 weeks. From the fourth week an accelerated hyperfractionated schedule was used as 2 x 1.4 Gy/day five days weekly given exclusively to the first order target volume of macroscopic tumor (adding up to a total dose of 72 Gy in six weeks). The second and third order target volumes received conventional fractionation only to 60 Gy and 50 Gy, respectively. The moderate acceleration of the concomitant boost scheme in the second half was counterbalanced during the first week by the introduction of a 5-fluorouracil bolus of 350 mg/M2 with 200 mg/M2 folinic acid and a subsequent continuous infusion using the same dose each 24 h for 5 days. Additionally, a Mitomycin-C bolus of 10 mg/M2 was infused at the fifth day and on the first day of the sixth week. Six weeks after treatment the patients were restaged. In cases with residual carcinoma salvage surgery was performed (11 patients). Late effects of therapy were analyzed according to the Lent-Soma index and life quality according to the European Organisation for Research and Treatment of Cancer-Module. Late effects of treatment were tolerable and were controlled locally. The 3-year-survival rate was 39%, with a local-regional recurrence-free control rate of 71%. Fifty-two percent of all cases of death were caused by distant metastases, secondary carcinomas or other diseases not related to tumor recurrence. The poor prognosis of hypopharyngeal carcinomas despite acceptable local tumor control may be due to specific biological factors present in affected patients.     

Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study

PURPOSE: Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced NSCLC received six weekly administrations of a CDDP-paclitaxel combination with concurrent local RT. The starting doses of CDDP and paclitaxel were 30 mg/m2/wk and 35 mg/m2/wk, respectively. RT was initially given at the dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (total dose, 60 Gy) and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last two cohorts of patients. The drug doses were escalated alternately until DLT occurred in more than one third of the patients in a given cohort. RESULTS: Overall, 25 patients were recruited through five different cohorts. All were assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of 25 patients (64%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk), two of five patients had to discontinue treatment because of severe esophagitis and one of these died of complications related to grade 4 esophagitis. However, keeping the same doses of chemotherapy and replacing hyperfractionation with a standard single-day fraction, weekly doses of CDDP and paclitaxel of 35 mg/m2 and 45 mg/m2 could be safely administered. Neutropenia was by far the most relevant hematologic toxicity and occurred in 33 of 141 weekly delivered courses, but it was of grade 4 in only four courses. Substantial pulmonary or neurologic toxicity was not observed in this study. Two complete responses (CRs) and 13 partial responses (PRs) were observed, for a 60% overall response rate (95% confidence interval [CI], 39% to 79%). The median survival time was 16 months, with a 66% 1-year survival probability. CONCLUSION: CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk can be safely administered with concurrent standard RT. The use of hyperfractionation is associated with a more frequent occurrence of severe esophagitis and requires a reduction of the CDDP dose to 30 mg/m2/ wk. Only future randomized trials will elucidate which of these two approaches (standard or hyperfractionated RT) is the better option to improve the outcome of patients with locally advanced NSCLC.