Locoregional recurrence risks in elderly breast cancer patients treated with mastectomy without adjuvant radiotherapy

This study examined tumour and treatment characteristics in elderly women treated with mastectomy without radiotherapy and compared their outcomes to younger counterparts. Data were analysed for 2362 women aged 50 years and older referred to the British Columbia Cancer Agency, Canada between 1989 and 1997. The women had invasive T1-4, N0-N3, M0 breast cancer treated with mastectomy without adjuvant radiotherapy. Clinical characteristics and patient outcomes were compared between two age cohorts: 50-69 (n = 1423) and 70+ years (n = 939). Median follow-up was 8.3 years. Tumours > 5 cm were present in 5% of women aged 50-69 and 3.5% of women aged 70+, respectively. The distribution of nodal stage was similar in the two age cohorts but older women were more likely to have fewer axillary nodes removed (P = 0.009). Fewer women aged 70+ had grade III histology (P = 0.002) and estrogen receptor (ER)-negative status (P < 0.001). The rates of systemic therapy use were comparable in the two age groups. With tumours > 5 cm, locoregional recurrence (LRR) were 13.7% and 30.0% in women aged 50-69 and 70+, respectively. With 1-3 positive nodes (N+), LRR were 14.8% and 13.0% in women aged 50-69 and 70+. In the presence of 4 N+, LRR were 16.8% and 30.8% in women aged 50-69 and 70+. On multivariate analysis, age was not significantly associated with LRR (P = 0.62). Independent prognostic factors for LRR were grade III histology, lymphovascular invasion and positive nodal status. This study suggests that despite more favourable tumour characteristics and comparable systemic therapy use, women aged 70+ years have similar or higher postmastectomy LRR risks compared to younger women. Chronologic age alone should not preclude these women from consideration of adjuvant radiotherapy.     

Breast cancers, apparently non-metastatic, treated by prior chemotherapy and radiotherapy, combined with or without excision surgery. Preliminary results

Combined treatment modality was applied in 51 consecutive patients with locally advanced breast carcinoma between December 1982 and December 1984. The treatment was started with 4 cycles of chemotherapy with combination of adriamycin, vincristine, 5-fluorouracil and cyclophosphamide. This was followed by high-energy radiotherapy (45 Gy to the breast and lymphatic areas), with or without surgery. After radiotherapy, the response rate was 76%: 39/51 (complete response 39%: 20/51). Twenty-nine patients (57%) were treated conservatively (20 treated by radiotherapy alone and 9 treated by tumorectomy with axillary dissection followed by interstitial implantation). For 22 patients (43%), the mastectomy with axillary dissection was necessary. The three year overall survival rate and disease free survival rate were 88, and 86%. Local recurrences occurred in one patient (2%). The toxicity with this combined treatment regime was low. The cosmetic results were acceptable when a conservative treatment was proposed.     

Locoregional recurrence of ovarian cancer: the place of surgery

Standard therapy for advanced ovarian cancer includes cytoreductive surgery associated with platin based chemotherapy. Secondary surgery for recurrent ovarian cancer remains controversial. Actually there is not randomized trial based on this question. Furthermore literature shows that patients with recurrent disease may derive a significant survival benefit from optimal debulking. The datas availables indicate that prolonged disease free interval and feasibility of complete surgical resection are the main prognosis criteria. Proper selection of patients with recurrent ovarian cancer is essential to improve the therapeutic benefit of secondary surgery. There is a large place for trials and evaluation of innovatives techniques as hyperthermic intraperitoneal chemotherapy or intraperitoneal radio-immunotherapy.     

Locoregional recurrence of ORL cancer: the place of surgery

Surgery of locoregional failures is mainly represented by salvage surgery after radiotherapy. Due to progress of radiotherapy, especially modification of fractionation and association with chemotherapy, the problem of salvage surgery is nowadays emphasized. Despite the reduction of postoperative mortality and morbidity by the use of myocutaneous flaps the complications are still frequent and the rehabilitation long and difficult. Oncologic results are disappointing too, especially in salvage surgery for oropharyngeal and hypopharyngeal tumors with less than a half of patients being candidates for salvage surgery and 5 year survival rates inferior to 30% in these patients. Laryngeal tumors are more favorable for salvage surgery but in the majority of the cases recurrences after radiotherapy require a total laryngectomy. The poor postoperative, functional and oncologic results after salvage surgery, especially in pharyngeal tumors must be taken into account for the decision of primary treatment. Regarding the important locoregional aggressivity of squamous cell carcinomas of the upper aerodigestive tract, these results must be kept in mind when preservation protocols are in question.     

Isolated local-regional recurrence following mastectomy for adenocarcinoma of the breast treated with radiation therapy alone or combined with surgery and/or chemotherapy

The results of radiation therapy alone or combined with surgery and/or chemotherapy are reported for 47 patients who presented with local and/or regional recurrence without evidence of distant metastases following initial management of adenocarcinoma of the breast with radical or modified radical mastectomy (43) or simple mastectomy (4). Patients were treated between October 1964 and March 1983 at the University of Florida; all have a 2-year minimum follow-up and 42/47 (89%) have had follow-up for greater than or equal to 5 years. The overall actuarial local-regional control rates were 80% at 2 years, 68% at 5 years, and 61% at 10 years. The 5-year actuarial local-regional control rates by site and extent of disease were as follows: single chest wall nodule, 92%; multiple chest wall nodules, 49%; regional lymph nodes, 66%; and multiple sites, 64%. The 5- and 10-year actuarial determinate disease-free survival rates for all patients were 41 and 17%, respectively. The 5- and 10-year actuarial survival rates for all patients were 50 and 34%, respectively.     

Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group.

PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.     

Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence

PURPOSE: This study sought to review a single-institution experience with the management of adenoid cystic carcinoma of the head and neck. METHODS AND MATERIALS: Between 1960 and 2004, 140 patients with adenoid cystic carcinoma of the head and neck were treated with definitive surgery. Ninety patients (64%) received postoperative radiation to a median dose of 64 Gy (range, 54-71 Gy). Distribution of T stage was: 26% T1, 28% T2, 20% T3, and 26% T4. Seventy-eight patients (56%) had microscopically positive margins. Median follow-up was 66 months (range, 7-267 months). RESULTS: The 5- and 10-year rate estimates of local control were 88% and 77%, respectively. A Cox proportional hazards model identified T4 disease (p = 0.0001), perineural invasion (p = 0.008), omission of postoperative radiation (p = 0.007), and major nerve involvement (p = 0.02) as independent predictors of local recurrence. Radiation dose lower than 60 Gy (p = 0.0004), T4 disease (p = 0.005), and major nerve involvement (p = 0.02) were predictors of local recurrence among those treated with surgery and postoperative radiation. The 10-year overall survival and distant metastasis-free survival were 64% and 66%, respectively. CONCLUSION: Combined-modality therapy with surgery followed by radiation to doses in excess of 60 Gy should be considered the standard of care for adenoid cystic carcinoma of the head and neck.     

Adenocarcinoma of the endometrium treated with combined irradiation and surgery: study of 437 patients

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. METHODS AND MATERIALS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). CONCLUSION: Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.     

Long-term results of local excision with and without chemoradiation for adenocarcinoma of the rectum

The role of local excision for rectal carcinoma remains controversial. We reviewed 285 patients undergoing curative resection for rectal cancer between 1984 and 2001. Surgical procedures were local excision (LE; n = 49), abdominoperineal resection (APR; n = 124), and low anterior resection (LAR; n = 112). Median follow-up for all patients was 6.2 years. For patients undergoing local excision, postoperative tumor stages were Tis (22%), T1 (41%), T2 (18%), and T3 (18%). Twelve patients received postoperative radiation >/= 45 Gy, and 4 patients received adjuvant chemotherapy. Of the 49 patients who underwent LE, the 5- and 10-year overall survival rates were 76% and 42%, respectively. The 5- and 10-year disease-free survival rates were 69% and 58%, respectively. The incidence of local recurrence was 16% and the incidence of distant recurrence was 6%. For the 11 patients who experienced disease recurrence, the median time to recurrence was 13 months (range, 1-59 months). Of the 8 patients who developed local recurrence, 4 refused salvage treatment, 2 underwent salvage APR, and 2 underwent repeat excision. Of the 4 who underwent salvage surgery, one is alive with no evidence of disease, one developed distant disease, and 2 died with unknown disease status. Adjuvant therapy did not affect survival or recurrence rates in patients undergoing LE compared with other surgeries. The rate of local failure (16%) is comparable to that observed in the Cancer and Leukemia Group B (CALGB) 8984 prospective study and suggests that highly selected patients undergoing local excision can expect good local control of rectal cancer.     

Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy

PURPOSE: To evaluate prospectively the impact of combination chemotherapy in the combined modality treatment of isolated first locoregional recurrence (LRR) following mastectomy for breast cancer. METHODS AND MATERIALS: Between 1979 and 1989, 120 chemotherapy-naive women with isolated LRR as first failure after mastectomy were prospectively identified, uniformly staged, and systematically followed. Treatment consisted of excision if feasible, radical locoregional radiotherapy, and a hormonal maneuver (unless estrogen receptor negative). The initial chemotherapy cohort also received 8 cycles of doxorubicin and cyclophosphamide. This was compared to a subsequent control cohort. RESULTS: For all patients, the 10-year actuarial relapse-free survival +/- 95% confidence interval was 42.1+/-9.2%, and overall survival was 56.8+/-9.1%. No difference was seen in locoregional control between cohorts. At 5 years, distant recurrence-free survival for chemotherapy and control cohort respectively was 75.4+/-10.8% and 60.7+/-12.5% (p = 0.33) and overall survival was 81.9%+/-9.6 and 74.3%+/-11.2 (p = 0.24). Univariate analysis showed no prognostic importance for any imbalance between cohorts. Cox modeling confirmed that complete resection was strongly associated with fewer LRR (hazard ratio [HR] 0.32, p = 0.001) and also with better overall survival (HR 1.82, p = 0.019). Chemotherapy produced a substantial reduction in risk of death (HR 0.72 CI 0.421-1.235, p = 0.23). CONCLUSIONS: In this prospective but nonrandomized study of treatment for first LRR, the risk of death in the later control cohort was 1.39 times the risk in the chemotherapy cohort but failed to reach statistical significance. The results justify further study.     

Patterns of recurrence in bladder cancer treated by irradiation and/or cystectomy

Between 1949 and 1971, 451 patients with bladder cancer were treated by radiation therapy and/or radical cystectomy at the Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment for 137 patients in Group 1. In Group 2, 109 patients received radiation therapy to an average tumor dose of 6000 rad in 6 weeks ± 1 year before radical cystectomy for persistent, recurrent or new lesions. Planned preoperative irradiation consisted of either 4000 rad in 4 weeks for 119 patients in Group 3, or 2000 rad in 1 week for 86 patients in Group 4, ± 6 weeks and 2 days, respectively, before radical cystectomy.The determinate over-all distant and/or local recurrence rate was 49% for Group 1 and 37–45% for Groups 2–4. Local recurrence alone occurred in 28% of Group 1 patients and 14–16% of those in Groups 2–4. Distant metastases developed in 21% of Group 1 patients and 22–28% of Group 2–4 patients. A reduced incidence of pelvic recurrence was associated with radiation-induced stage reduction for Group 2–4 clinically high and low stage tumors, especially when the histologic grade was high. Similar frequencies of extrapelvic metastases in the four groups were maintained in clinically low and high stage tumors of low or high histological grade.     

Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation

We evaluated the 10- to 15-year outcome of 252 patients with small-cell lung cancer entered into therapeutic clinical trials with or without chest and cranial irradiation. Thirty-two patients (13%) survived free of cancer for 2 or more years. Twelve patients (5%) survived at least 10 years free of cancer, and 10 patients are currently alive and free of cancer beyond 10 years. Six of these 10 patients currently function at a level comparable with that before diagnosis. The other 22 patients who were cancer-free at 2 years have died. Nine patients died from recurrent small-cell lung cancer 2 to 6.2 years after initiation of chemotherapy. Five died from non-small-cell lung cancer, three died of other malignancies, and five died of causes other than cancer. A small fraction of patients with small-cell lung cancer are cured of their original malignancy, but these patients remain at high risk for second cancers and death from other causes.     

Locoregional irradiation for inflammatory breast cancer: effectiveness of dose escalation in decreasing recurrence

Purpose: To evaluate the effect of radiation dose escalation on locoregional control, overall survival, and long-term complication in patients with inflammatory breast cancer.

Patients and Methods: From September 1977 to December 1993, 115 patients with nonmetastatic inflammatory breast cancer were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. The usual sequence of multimodal treatment consisted of induction FAC or FACVP chemotherapy, mastectomy (if the tumor was operable), further chemotherapy, and radiation therapy to the chest wall and draining lymphatics. Sixty-one patients treated from September 1977 to September 1985 received a maximal radiation dose of 60 Gy to the chest wall and 45–50 Gy to the regional lymph nodes, 22 treated once a day at 2 Gy per fraction, and 35 were treated b.i.d. (32 after mastectomy and all chemotherapy was completed, and 2 immediately after mastectomy; one patient had distant metastases discovered during b.i.d. irradiation, and treatment was stopped). Four additional patients received preoperative radiation with standard fractionation. Based on the analysis of the failure patterns of the patients, the dose was increased for the b.i.d. patients in the new series, with 51 Gy delivered to the chest wall and regional nodes, followed by a 15-Gy boost to the chest wall with electrons. From January 1986 to December 1993, 39 patients were treated b.i.d. to this higher dose after mastectomy and all the chemotherapy was completed; and 8 additional patients received preoperative irradiation with b.i.d. fractionation to 51 Gy. During this period, another 7 patients were treated using standard daily doses of 2 Gy per fraction to a total of 60 Gy, either because they had a complete response or minimal residual disease at mastectomy or because their work schedule did not permit the b.i.d. regimen. Comparison was made between the groups for locoregional control, disease-free and overall survival, and complication rates.

Results: The median follow-up time was 5.7 years (range, 1.8–17.6 years). For the entire patient group, the 5- and 10-year local control rates were 73.2% and 67.1%, respectively. The 5- and 10-year disease-free survival rates were 32.0% and 28.8%, respectively, and the overall survival rates for the entire group were 40.5% and 31.3%, respectively. To evaluate the effectiveness of dose escalation, a specific comparison of patients who received b.i.d. radiation after mastectomy and completion of adjuvant chemotherapy was performed. There were 32 patients treated b.i.d. to 60 Gy in the old series versus 39 patients treated b.i.d. to 66 Gy in the new series. There was an significant improvement in the rate of locoregional control for the b.i.d. patients for the old vs. new series, from 57.8% to 84.3% and from 57.8% to 77.0% (p = 0.028) at 5 and 10 years, respectively. Chemotherapy regimens did not change significantly during this time period.

Long-term complications of radiation, such as arm edema more than 3 cm (7 patients), rib fracture (10 patients), severe chest wall fibrosis (4 patients), and symptomatic pneumonitis (5 patients), were comparable in the two groups, indicating that the dose escalation did not result in increased morbidity. Significant differences in the rates of locoregional control (p = 0.03) and overall survival (p = 0.03), and a trend of better disease-free survival (p = 0.06) were also observed that favored the recently treated patients receiving the higher doses of irradiation.

Conclusion: Twice-daily postmastectomy radiation to a total of 66 Gy for patients with inflammatory breast cancer resulted in improved locoregional control, disease free survival, and overall survival, and was well tolerated.     

Locoregional recurrence of breast cancer: a retrospective comparison of irradiation alone versus irradiation and systemic therapy.

The role of systemic therapy in addition to irradiation for locoregional recurrence of breast cancer is controversial. In the absence of prospective randomized trials, treatment decisions must be based on retrospective studies. We retrospectively analyzed 230 patients treated for locoregionally recurrent breast cancer between 1964 and 1986. Forty-seven were premenopausal, 173 were postmenopausal, and the menopausal status was unknown in 10 patients. Each patient treated with radiotherapy (RT) and chemotherapy or with RT and hormonal therapy was matched with a control patient treated with RT alone. The addition of hormonal therapy to radiation therapy significantly improved the 5-year overall survival (50 versus 28%), disease-free survival (37 versus 26%), and distant metastases-free survival (45 versus 29%). No improvement in locoregional control was observed. In contrast, chemotherapy did not confer such survival benefits, but there was a trend towards improvement in 5-year locoregional control (68 versus 50%), p = 0.08. Our data support the use of hormonal therapy along with RT at the time of locoregional recurrence of breast cancer. Although our data suggest that chemotherapy is not routinely indicated, controlled clinical trials are needed to define which subsets of patients, if any, benefit from systemic therapy.     

Retromolar trigone squamous cell carcinoma treated with radiotherapy alone or combined with surgery

BACKGROUND: Treatment outcomes were analyzed for retromolar trigone squamous cell carcinoma. METHODS: Between June 1966 and August 2003, 99 patients were treated with radiotherapy alone (35 patients) or radiotherapy combined with surgery (64 patients). Followup ranged from 0.2 to 23.8 years (median, 3.3 yrs). All living patients had followup for at least 1 year. RESULTS: The 5-year local-regional control rates after definitive radiotherapy versus surgery and radiotherapy were as follows: Stages I-III, 51% and 87%; Stage IV, 42% and 62%; and overall, 48% and 71%, respectively. The 5-year cause-specific survival rates after definitive radiotherapy compared with surgery and radiotherapy were as follows: Stages I-III, 56% and 83%; Stage IV, 50% and 61%; and overall, 52% and 69%, respectively. Multivariate analyses revealed that the likelihood of cure was better with surgery and radiotherapy compared with definitive radiotherapy. CONCLUSIONS: The likelihood of cure after treatment for retromolar trigone squamous cell carcinoma was influenced by the extent of disease and treatment. Patients treated with surgery and radiotherapy had a better outcome than those treated with radiotherapy alone.