Prognosis following local recurrence in the conservatively treated breast cancer patient

At Yale-New Haven Hospital conservative treatment of early stage breast carcinoma with lumpectomy and radiation therapy has been used with increasing frequency since the 1960s. We have reviewed our experience with specific reference to prognosis following local recurrence. Between January 1962 and December 1984 a total of 433 patients were treated with conservative surgery and radiation therapy using standard techniques. As of December 1989, with minimum evaluable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 ipsilateral breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Extent of disease at the time of local recurrence was clinically categorized as localized (less than 3 cm without dermal involvement) or diffuse (greater than 3 cm and/or with dermal involvement). Seventy-two percent of the recurrences were at or near the original tumor site whereas 28% recurred elsewhere in the breast. At a median follow-up post recurrence of 5.0 years (range 0.3-16.9 years), the 5-year actuarial survival for breast recurrences was 59% and the 5-year disease-free survival was 65%. A number of clinical and pathological features at the time of original diagnosis as well as at the time of local recurrence were tested as possible prognostic indicators for survival following local recurrence. By univariate analysis, significant factors associated with survival following local recurrence included extent of local disease at the time of recurrence (p less than .01), time to local recurrence (p less than .03), with later recurrences doing better, and site of local recurrence (p less than .01), with recurrences elsewhere in the breast doing better. We conclude from this large single institutional experience with a median follow-up post-recurrence of over 5 years that patients experiencing a local recurrence in the conservatively treated breast have a relatively favorable prognosis. The prognostic factors correlating with survival and implications regarding adjuvant systemic therapy at the time of local recurrence are discussed.     

A clinical and histopathologic analysis of the results of conservation surgery and radiation therapy in stage I and II breast carcinoma

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

Testicular seminoma. Results of the Yale University experience, 1964-1984

Eighty-three testicular seminoma patients were treated with radiation therapy from 1964 through 1984. Seventy-nine (95%) of the 83 patients had early disease that included 61 Stage I, 15 Stage IIA (pelvic or paraaortic lymph node involvement less than or equal to 5 cm), and 3 Stage IIB (pelvic or paraaortic lymph node involvement greater than 5 cm) patients. The 15-year actuarial survival for this group of Stage I and II patients was 95% (+/- 5%). Stage I patients were treated with a mean paraaortic/pelvic dose of 2924 cGy and only one patient developed recurrent disease. This recurrence was at the margin of the radiation field and probably represents a marginal miss. The Stage IIA patients were treated with slightly higher doses (mean, 3335 cGY) to the paraaortic/pelvic region and there were no recurrences. The three Stage IIB patients received tumor doses of 3245 cGy, 4090 cGy, and 4500 cGy, respectively, and there were no recurrences. Low dose prophylactic mediastinal and supraclavicular irradiation (mean, 2320 cGy) was used in 17 (94%) of the 18 Stage II patients and there were no mediastinal or supraclavicular recurrences. Four patients presented with advanced disease (one Stage III, three Stage IV) and the only disease-free survivor was treated with cisplatinum-based combination chemotherapy and radiation therapy. Three patients developed minor complications from the radiation therapy: one patient had persistent scrotal and leg edema and two patients treated with prophylactic mediastinal irradiation had chronic low leukocyte counts. Two of the 79 Stage I and II patients developed a second malignancy: one had bronchogenic carcinoma at the margin of a mediastinal field, and one had diffuse histiocytic lymphoma both in and out of the radiation therapy fields. The 15-year actuarial probability of developing a second malignancy was 3.3%. Radiation therapy after operation is a successful treatment option for most patients with Stage I and II seminoma.     

Conservation therapy for breast cancers other than infiltrating ductal carcinoma

Pathologic review of 861 Stage I and II breast cancers yielded 152 patients (18%) with histologic types other than invasive ductal carcinoma. All patients had been treated by breast-conserving surgery and radiotherapy, including supplemental radiation to the tumor bed. For 67 patients with predominantly lobular carcinomas, the actuarial overall 5-year survival was 100% and 77% for node-negative and node-positive patients, respectively. The actuarial probability of recurrence in the treated breast (13.5% at 5 years) appeared to be somewhat greater than that observed after treatment of invasive ductal cancers (8.8% at 5 years, P = 0.11). Of 12 mammary recurrences in patients with lobular carcinoma, four occurred at a considerable distance from the original primary and seven were multifocal, involving more than one quadrant in five patients. Of 47 patients with strictly in situ carcinomas, one patient whose axillary nodal status had not been determined subsequently developed distant metastases. Three additional patients developed mammary recurrence, two at the primary tumor site and one in another quadrant. The actuarial 5-year mammary recurrence and overall survival rates were 4% and 98%, respectively. For 27 patients with true medullary cancers, overall survival at 5 years was 90%. One localized mammary recurrence was observed at the site of the original primary. Actuarial mammary recurrence rate was 4% at 5 years. No relapse was observed in ten patients with colloid and one patient with adenoid cystic carcinoma. The authors conclude that, in addition to its well-established efficacy in the treatment of infiltrating ductal carcinomas, the combination of tumor excision and radiotherapy appears to provide adequate local control for other histologic types as well. However, patients with lobular cancer appear to be at somewhat greater risk of mammary failure, and recurrences in such patients tend to be multifocal and multicentric.     

Primary radiation therapy for locally advanced breast cancer

The optimal local-regional treatment for patients with Stage III breast cancer has not been determined. To evaluate the effectiveness of radiation therapy as local treatment for such patients, the results of 192 patients (five with bilateral disease) treated with radiation therapy without mastectomy between July 1, 1968 and December 31, 1981 were reviewed. Excisional biopsy (gross tumor removal) was performed in only 54 of the 197 breasts. Patients typically received 4500 to 5000 cGy in 5 weeks to the breast and draining lymph nodes; a local boost to areas of gross disease was delivered to 157 patients. Multi-agent chemotherapy was given to 53 patients. The median follow-up was 65 months. The actuarial probability of survival for the entire group was 41% at 5 years and 23% at 10 years. The probability of relapse-free survival (RFS) was 30% at 5 years and 19% at 10 years. The addition of multi-agent chemotherapy was associated with a significantly improved 5-year RFS (40% versus 26%, P = 0.02). The 5-year survival rate was 51% for patients who received adjuvant multi-agent chemotherapy and 38% for patients who did not (P = 0.16). The actuarial rate of local-regional tumor control (not censored for distant failure) for all patients was 73% at 5 years and 68% at ten years, and the crude incidence of local-regional control was 78%. Local-regional tumor control was principally influenced by radiation dose. Patients who received 6000 cGy or greater to the primary site had a better 5-year rate of control in the breast than did patients who received less than 6000 cGy (83% versus 70%, P = 0.06). Significant complications were seen in 15 patients (8%); these included moderate or severe arm edema in six patients and brachial plexopathy in four patients. Cosmetic results at last evaluation were excellent or good in 56% of evaluable patients, fair in 25%, and poor in 19%. It is concluded that high-dose radiation therapy without mastectomy is an effective means of controlling local-regional tumor in patients with locally advanced breast cancer.     

Local recurrence after breast-conserving surgery and radiotherapy. Frequency, time course, and prognosis

Mammary recurrences were studied in 1593 patients with Stage I and II breast cancer treated by macroscopically complete tumor excision followed by megavoltage radiotherapy, including a boost to the tumor bed (mean dose, 78 Gy). The actuarial freedom from mammary recurrence was 93% at 5, 86% at 10, 82% at 15, and 80% at 20 years. Seventy-nine percent of the recurrences were in the vicinity of the tumor bed, but with increasing time interval, an increasing percentage of recurrences was located elsewhere in the breast. A majority of recurrences after 10 years could be considered new tumors. Only ten of 181 patients with recurrence had prior or concomitant distant metastases, and 159 of 171 isolated mammary recurrences (93%) were operable. Uncorrected overall survival after operable recurrence was 69% at 5 and 57% at 10 years. Prognosis after late recurrence (after 5 years) was favorable (84% 5-year survival). Operable early recurrences retained a favorable prognosis if smaller than 2 cm and confined to the breast (74% 5-year survival). Disease-free interval and histologic grade also appeared to be important prognostic factors after early recurrence. Survival after recurrence did not depend upon the type of salvage operation. Locoregional control was 88% at 5 years after salvage mastectomy and 64% after breast-conserving salvage procedures. The role of adjuvant systemic therapy at time of local recurrence requires additional study. This experience illustrates the important differences between mammary failure and chest wall recurrence after mastectomy, in particular the protracted time course and more favorable prognosis associated with the former.     

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.     

Biopsy and definitive radiation therapy in stages I and II carcinoma of the female breast

One hundred-twenty patients with Stages I and 11 carcinoma of the female breast were treated by biopsy followed by definitive radiation therapy without mastectomy. The breast received 4500–5000 cGy (rad) using a 6 MV the area of the primary tumor of 2000 cGy (rad) using electrons in 99 patients (83 % ) and interstitial implantation in 21 patients (17 % ). Local recurrence was not recorded in the 43 patients with Stage I disease, while three of 77 patients (41%) with Stage II disease suffered a local recurrence. The actuarial five-year relapse-free survival was 91 % and 60 % in Stages I and II respectively. Cosmetic results were considered excellent by both physician and patient in the majority of cases. Axillary dissection was the recommended method of staging the axilla but was noted to be more morbid than axillary sampling. Electrons may be as effective as interstitial implantation as a means of supplementation following external beam therapy if specific guidelines are followed.     

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)     

Vaginal recurrences of endometrial carcinoma: the prognostic value of staging by a primary vaginal carcinoma system

Fifty-five of 1716 women with endometrial carcinoma seen consecutively at three institutions prior to 1986 were found to have an isolated post-hysterectomy vaginal recurrence. Their therapy included external radiation therapy (RT) and brachytherapy for 26 women, external RT alone for 17, brachytherapy only for 4, and no RT for 8. Combined external RT/brachytherapy doses ranged from 2000 to 10,000 cGy with a median of 6000 cGy. The 3- and 5-year actuarial survival rates are 48% and 31% for the entire group, and the 3- and 5-year pelvic control rates are 52% and 42%. The 5-year survival and pelvic control rates for those who received greater than or equal to 6000 cGy in total RT dose are 47% and 68%, compared with 12% and 10% for those receiving less than 6000 cGy (p = 0.002 and p = 0.004). For patients receiving their second RT course, the 5-year survival rate is 16%, compared with 48% for those not previously irradiated. The Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma was applied to each recurrence. There were 15 Stage I cases (vaginal mucosa), 32 Stage II cases divided between 15 Stage IIA (subvaginal infiltration) and 17 in Stage IIB (parametrial infiltration), and 8 Stage III cases (pelvic wall involvement). The 3-year actuarial survival and pelvic control rates using this staging system are: Stage I: 85%/100%; Stage II: 41%/43%, Stage IIA: 59%/53%, Stage IIB: 26%/35%; Stage III: 13%/0%. These outcome endpoints are significantly better for Stage I than Stage II patients (p = 0.01 & 0.0004) and for Stages I and IIA compared to Stages IIB and III (p = 0.0005 & 0.002). The pre-treatment variables of age, interval since hysterectomy, initial stage, and location did not predict for survival, but a higher rate of pelvic control was observed for apical than for suburethral recurrences (56% vs. 20%). Grade III histology was highly correlated with poor survival (p = 0.0006). This vaginal carcinoma staging system appears to have value in predicting treatment outcome for patients with post-hysterectomy vaginal recurrences.     

Outpatient follow-up after treatment for early breast cancer: updated results after 5 years

The value of frequent outpatient follow-up in the first few years after primary treatment for early breast cancer is a controversial issue. Schedules involving 3-4 monthly visits in the first 2-3 years and 6-monthly from years 3-5 are still commonplace. In this study we audited such a policy from a single cancer centre, identifying a cohort of all 612 patients with early breast cancer (pT(1-3)pN(0-1)NxM0) referred for adjuvant therapy in 1993. The hospital records were reviewed to ascertain patient and tumour characteristics, the surgical and adjuvant treatment received, the timing and sequencing of recurrences and their mode of detection. Five hundred and five patients had breast conservation surgery. The actuarial local recurrence-free survival rate at 5 years in this group was 94.5%. Twenty-five of the 31 local recurrences that occurred were the first site of relapse. Eight (32%) of these were detected at routine clinic appointments, seven (28%) by routine mammography, and nine (36%) were interim referrals. Significant risk factors for local recurrence identified were lymph node status (P = 0.03) and tumour grade (P = 0.04). One hundred and four patients underwent mastectomy. The actuarial local recurrence-free survival at 5 years in this group was 85.4%. Nine of the 13 local recurrences were the first site of relapse. Six (66.7%) of these were detected at routine appointments. The significant risk factor for local recurrence identified was tumour grade (P = 0.03). Overall, 60.1% of metastases presented as interim referrals. Nodal status, tumour grade and tumour stage were confirmed as significant risk factors for metastasis (P < or = 0.001). Hazard rate analysis demonstrated a peak incidence of both local and metastatic recurrences in the second year, diminishing thereafter. This peak was largely confined to patients with tumours with poor prognostic features. We identified only eight patients out of a total of 612 followed up as outpatients for 5 years who had local recurrences that were detected at routine appointments and were amenable to salvage surgery with the prospect of cure. Therefore it is unlikely that a reduction in the intensity of outpatient follow-up in the early years after primary treatment will have a significant impact on the overall mortality or morbidity of patients with early breast cancer. Other models of follow-up are discussed, which could work well provided good communication is maintained amongst the health care professionals involved.     

Conservation therapy for invasive lobular carcinoma of the breast.

Earlier literature suggests a high incidence of multicentricity and bilaterality, with an overall poor prognosis, in patients with invasive lobular carcinoma of the breast. Consequently, there is considerable disagreement regarding appropriate local management of this disease. To determine the influence of invasive lobular histologic findings on local tumor control, disease-free survival, and overall survival, the authors reviewed 60 patients with Stage I and II invasive lobular breast carcinoma treated with local tumor excision and radiation therapy between 1981 and 1987 (mean follow-up, 5.5 years; range, 2.5 to 10 years). The 5-year actuarial risk of locoregional recurrence was 5%, with two of three failures occurring in the regional lymphatics. The mean time to locoregional failure was 28 months. The 5-year actuarial disease-free survival (84%) and overall survival (91%) were comparable to those seen in several large series of similarly treated patients with invasive ductal carcinoma. Contralateral breast cancer occurred at a rate of approximately 0.6% per year. This study and a review of the literature suggest that breast conservation, with local resection and radiation therapy, is appropriate therapy for invasive lobular breast cancer.     

Long-term follow-up of radiotherapy for prostate cancer

PURPOSE: To determine the long-term outcome of radiotherapy for prostate cancer. METHODS AND MATERIALS: A total of 136 consecutive patients with prostate cancer underwent primary radiotherapy. All but 4 patients received 6000 cGy to the prostate. The minimal follow-up was 22.9 years. RESULTS: Of the 136 patients, 93 had Stage B (T2), 9 Stage A (T1), and 34 Stage C (T3). Sixty-nine percent of the patients developed recurrence, and 51% of all patients died of prostate cancer. The recurrences developed at a steady state throughout the length of follow-up. One half the recurrences occurred after 10 years, and recurrence was still observed >20 years after treatment. The survival rate at 5, 10, 15, 20, and 25 years was 81%, 59%, 37%, 16%, and 10%, respectively. The recurrence-free survival rate at 25 years was 17%. The median survival for Grade 3-4 patients was 6.3 years and for Grade 1-2 patients was 13.0 years. The median survival for those with T1 tumors was 12.9 years; T2 tumors, 12.4 years; and T3 tumors, 9.5 years. CONCLUSION: Despite favorable early results, with long-term follow-up, patients continued to experience prostate cancer recurrence. Unless they died an intercurrent death, they were highly likely to develop recurrence and die of prostate cancer. The conclusions from treatment studies with <15 years of follow-up should be viewed as preliminary.     

Pattern of local recurrence after conservative surgery and whole-breast irradiation

PURPOSE: Most recurrences in the breast after conservative surgery and whole-breast irradiation have been reported to occur within the same quadrant as the initial primary tumor. We analyzed the long-term risk of recurrence by area of the breast after whole-breast irradiation. MATERIALS AND METHODS: In all, 1,990 women with Stage 0-II breast cancer were treated with conservative surgery and whole-breast irradiation from 1970-1998. Stage was ductal carcinoma in situ in 237, T1 in 1273, and T2 in 480 patients. Of 120 local recurrences, 71 were classified as true local (confined to the original quadrant) and 49 as elsewhere (involving outside the original quadrant). Kaplan-Meier methodology was used to calculate 5-year, 10-year, and 15-year rates of recurrence (95% confidence intervals in parentheses). The median follow-up is 80 months. RESULTS: There was no apparent difference in the 15-year rate of true local vs. elsewhere recurrence, but the time to recurrence was different. The rate of true local recurrence was 2%, 5%, and 7% (5-9%) at 5, 10, and 15 years, respectively. The recurrences elsewhere in the breast were rare at 5 (1%) and 10 (2%) years, but increased to 6 (3-9%) at 15 years. This 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers of 13% (10-16%). CONCLUSIONS: Recurrence elsewhere in the breast is rare for the first 10 years, but by 15 years is nearly equal to true local recurrence even after whole-breast irradiation. The 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers. This may indicate a therapeutic effect of whole-breast radiation for other areas of the breast. Very long follow-up will be needed for partial breast irradiation with or without tamoxifen to show that the risk of elsewhere recurrence is not significantly different than after whole-breast irradiation.     

Mammographic, pathologic, and treatment-related factors associated with local recurrence in patients with early-stage breast cancer treated with breast conserving therapy

BACKGROUND: We retrospectively reviewed our institution's experience treating early-stage breast cancer patients with breast conserving therapy (BCT) to determine clinical, pathologic, mammographic, and treatment-related factors associated with outcome. METHODS: Between January 1980 and December 1987, 400 cases of Stage I and II breast cancer were managed with BCT at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent at least an excisional biopsy. Radiation treatment consisted of delivering 45-50 Gy to the whole breast, followed by a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up in the 292 surviving patients is 118 months. Multiple clinical, pathologic, mammographic, and treatment-related factors were analyzed for an association with local recurrence and survival. RESULTS: A total of 37 local recurrences developed in the treated breast, for a 5- and 10-year actuarial rate of 4% and 10%, respectively. On univariate analysis, patient age < or =35 years (25% vs. 7%, p = 0.004), and positive surgical margins (17% vs. 6%, p = 0.018) were associated with an increased risk of local recurrence at 10 years. On multivariate analysis, only age < or = 35 years remained significant. A subset analysis of 214 patients with evaluable mammographic findings was performed. On univariate analysis, age < or = 35 years (38% vs. 8%, p = 0.0029) and the presence of calcifications on preoperative mammography (22% vs. 6%, p = 0.0016) were associated with an increased risk of local recurrence. On multivariate analysis, both of these factors remained significant. The presence of calcifications on preoperative mammography did not affect the rates of overall survival, disease-free survival, and cause-specific survival. CONCLUSION: In patients with early-stage breast cancer treated with BCT, age < or = 35 years and calcifications on preoperative mammography appear to be associated with an increased risk of local recurrence.     

Tumorectomy and radiotherapy in early breast cancer: a report on 392 patients

This study includes 392 patients (231 Stage I and 161 Stage II) treated by tumorectomy followed by radiotherapy. The overall actuarial survival for all the patients is 86.5% at 5 years and 78% at 10 years. The 5-year NED survival is 70.2%. The survival rates are depending on the loco-regional extension: Stage I: 92% survival at 5 years and 84% at 10 years; Stage II: 82% survival at 5 years and 75% at 10 years. The percentage of local recurrences were 13% for all stages (10.6% for Stage I, 16% for Stage II), of lymph node recurrences: 1.5% for all stages, 1.3% for Stage I, 2% for Stage II, of distant metastases: 11.2% for all stages, 8% for Stage I and 16% for Stage II. The loco-regional control rates were analyzed according to the TNM classification and discussed and compared to several literature data. The breast preservation rates were at 5 years 85% for Stage I and 80.9% for Stage II. Cosmetic results are judged as good in 80% by doctors and in 90% by patients themselves with very low complication rates.     

Breast relapse following primary radiation therapy for early breast cancer. I. Classification, frequency and salvage

Primary radiation therapy has become an accepted alternative to mastectomy for patients with early breast cancer. In order to improve the results of this treatment, we performed an analysis of failure on 366 clinical Stage I or II invasive breast carcinomas treated with primary radiation therapy. With a median follow-up of 52 months, there have been 30 recurrences in the treated breast, for a 5 year actuarial local recurrence rate of 9%. The recurrence rate was much higher for patients having less-than-excisional biopsy than for those undergoing excisional biopsy (35% vs. 7%, p less than 0.0001). Failures in the treated breast have been categorized as: true recurrence (TR), directly at the site of the primary; marginal miss (MM), at the edge of the boosted volume; and elsewhere in the breast (E). For patients having excisional biopsy, the actuarial probability of a true recurrence at 5 years was 4%. The risk of a true recurrence was related to the dose given to the primary site with rare true recurrences seen with doses greater than 6000 rad. The probability of a marginal miss at 5 years was 4%, and was not related to the dose or volume of the boost used. The probability of a recurrence elsewhere in the breast at 5 years was 1%. In patients treated with excisional biopsy and a total primary dose over 6000 rad, the probability of a local recurrence at 5 years was 4 and 10% for clinical Stage I and II patients respectively. These results indicate that primary radiation therapy provides a high likelihood of local tumor control and our analysis of failure suggests methods for decreasing each type of local recurrence.     

Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma. Brain metastases have been reported to be a common feature of Stage IV ASPS, and recent practice guidelines recommend routine intracranial imaging as part of the staging evaluation in all patients who present with ASPS. METHODS: The authors performed a comprehensive retrospective review of the clinical presentation, treatment, outcome, and patterns of failure in a consecutive series of patients with localized (American Joint Committee on Cancer [AJCC] Stages II/III) or metastatic (AJCC Stage IV) ASPS who presented to a tertiary care cancer center between 1959 and 1998. RESULTS: Seventy-four patients were identified from the database searches. The anatomic distribution of their primary tumors included: extremities, 44 patients (60%); trunk, 15 patients (20%); head and neck, 9 patients (12%); and retroperitoneum, 6 patients (8%). The median tumor size was 6.5 cm (range, 1.2-24 cm). The AJCC stage at presentation was Stage II or III in 35% of the patients and Stage IV in 65% of the patients. The 5-year actuarial local recurrence free, distant recurrence free, disease free, and overall survival rates among the 22 patients with localized ASPS were 88%, 84%, 71%%, and 87%, respectively. At a median follow-up of 9 years, 2 of 22 patients with localized disease had developed local recurrences and 3 had developed metastatic disease (all to the lung only). Brain metastases were noted in 9 of 48 patients who presented with Stage IV (M1) disease (19%) and always were noted in association with metastasis to other sites. The median survival of patients with M1 disease was 40 months, with a 5-year survival rate of 20%. CONCLUSIONS: Long term follow-up of patients with localized ASPS reveals a relatively indolent clinical course with relatively low rates of local and distant recurrence. In patients with Stage IV ASPS, brain metastases were observed only as part of more disseminated disease. The observations of the current study do not support current practice guidelines for the staging of patients with ASPS and suggest that selective rather than routine intracranial imaging should be used in patients presenting with ASPS.     

Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up

Between 1960 and 1980, 518 patients with T1, T2, N0, N1a, invasive breast cancer were treated by limited surgery at Institute Curie with (183 patients) or without (335 patients) axillary node dissection, followed by radiation therapy to breast and nodes. Median follow-up was 8.6 years (1.3 to 25 years). Fifty-six breast recurrences occurred, including 49 breast recurrences alone, 3 simultaneous breast and node recurrences, and 4 simultaneous breast recurrences and metastasis. Five-year, 10-year, and 15-year actuarial risks of breast recurrences were 7 +/- 1%, 11 +/- 1.5%, and 18 +/- 3%, respectively. Univariate analysis of 14 clinical and pathological prognostic factors revealed that local control in breast was significantly impaired by young age, premenopausal status, inadequate gross surgical excision, extensive ductal in situ component, and endolymphatic extension. On multivariate analysis with a Cox regression model, the most important contributors to local breast control in order of importance were age (p less than 10(-4), relative risk = 2.44), adequacy of surgery (p = 0.003, relative risk = 2.78), and endolymphatic extension (p = 0.03, relative risk = 2.98). The 5-year actuarial survival rate following breast recurrence was 73%, and was significantly worse when breast recurrence occurred in the first 3 years after treatment: 44% versus 87%, respectively (p less than 0.01). This study confirms the relationship between young age and low breast control rates, and demonstrates the importance of adequate initial surgical procedures. It emphasizes the adverse prognosis of early breast recurrences as compared to the relatively favorable outcome of late recurrences.     

Postoperative radiation therapy of rectal cancer

Beginning in December 1975, at the Massachusetts General Hospital (MGH) patients with rectal carcinomas thought to be at high risk of local recurrence after potentially curative surgical resection, were entered on a treatment protocol of high dose postoperative radiation therapy. Treatment was given with X rays of 10 MeV, generally using a four-field box technique to a dose of 4500 cGy with a boost to 5040 cGy or higher when the small bowel could be excluded from the reduced field. One-hundred sixty-five patients who began their radiation therapy between December 1975 and December 1982 were entered into the study. The median age was 65 years. The median follow-up in the survivors was 56 months, with a minimum follow-up of 17 months. All but 10 patients were followed for more than 2 years. Of the entire group, the actuarial 5-year survival was 53%, with survival of 71% in patients with Stage B-2, 39% in Stage C-2, and 17% in Stage C-3. Local failure was seen in 5/53 patients with Stage B-2 disease and 0/7 of patients with Stage B-3 disease. In patients with positive lymph nodes, local failure occurred in 2/10 (20%) of patients with Stage C-1, 16/77 (21%) of Stage C-2, and 8/15 (53%) of patients with Stage C-3 disease. Compared to previous series of surgery alone, the local failure rate has been decreased by more than one-half in all patients, except those with Stage C-3. Efforts to maximize the radiation doses in all stages should be made to minimize local failure. For Stage C-3, newer strategies such as intraoperative radiation therapy should be employed to decrease the continuing high incidence of failures.