F. A. Vicini

Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer

The frequency of brachial plexopathy, rib fracture, tissue necrosis, pericarditis, and second non-breast malignancies occurring in the treatment field among 1624 patients with early stage breast cancer treated with conservative surgery and radiation therapy at the Joint Center for Radiation Therapy between 1968 and 1985 is reported. The median follow-up time for survivors was 79 months (range 5-233 months). Brachial plexopathy was related to the use of a third field, the use of chemotherapy and the total dose to the axilla. Brachial plexopathy developed in 20 of 1117 women (1.8%) who received supraclavicular irradiation with or without axillary irradiation. The median time to its occurrence was 10.5 months (range 1.5-77 mo), and the majority (80%) of cases completely resolved. Among patients treated with a three-field technique, the incidence of brachial plexopathy was 1.3% (13/991) in patients treated with a dose to the axilla of less than or equal to 50 Gy, compared with 5.6% (7/126) in women treated with an axillary dose of greater than 50 Gy. The incidence of brachial plexopathy was 4.5% (15/330) among patients receiving chemotherapy, compared with 0.6% (5/787) when chemotherapy was not used (p less than 0.0001). Rib fracture was seen in 29 patients (1.8%), at a median time of 12 months following treatment (range 1-57). In all cases, the rib fracture healed without intervention. The incidence of rib fracture was 2.2% (28/1300) among patients treated on a 4 MV linear accelerator, compared with 0.4% (1/276) for patients treated on a 6 or 8 MV machine (p = 0.05). Of patients treated on a 4 MV machine, 0.4% (1/279) developed a rib fracture when a whole breast dose of 45 Gy or less was given, 1.4% (10/725) after receiving between 45 and 50 Gy, and 5.7% (17/296) following 50 Gy or higher. Tissue necrosis requiring surgical correction developed in three patients (0.18%) 22, 25, and 114 months after treatment. Presumed pericarditis (requiring hospitalization) was seen in 0.4% of women (3/831) who received radiation therapy to the left breast 2, 2, and 11 months after the start of treatment. Three women (0.18%) developed sarcomas in the treatments field at 72, 107, and 110 months, for a 10-year actuarial rate of 0.8%. Two of these sarcomas developed in areas of probable match-line overlap. One patient (0.06%) developed an in-field basal cell carcinoma at 42 months. In conclusion, the risk of significant complications following conservative surgery and radiation therapy for early stage breast cancer is low.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy

The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, we retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocenter from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002). A case:control analysis was performed to determine if the volume of lung irradiated (as determined using central lung distance [CLD]) was related to the risk of developing radiation pneumonitis. Three control patients were matched to each case of radiation pneumonitis based on age, side of lesion, chemotherapy (including sequencing), use of a third field, and year treated. Lung volumes were similar in the radiation pneumonitis cases and controls. We conclude that radiation pneumonitis following conservative surgery and radiation therapy for breast cancer is a rare complication, and that it is more likely to occur in patients treated with both a 3-field technique and chemotherapy (particularly given concurrently with radiation therapy). Over the limited range of volumes treated, lung volume was not associated with an increased risk of radiation pneumonitis.

Regional nodal failure after conservative surgery and radiotherapy for early-stage breast carcinoma.

We retrospectively analyzed the likelihood of regional nodal failure (RNF) for 1,624 patients with stage I or II invasive breast carcinoma treated with conservative surgery and radiotherapy (RT) at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. The median follow-up time was 77 months. RNF was the first site of failure for 38 of the 1,624 patients (2.3%). The incidence of axillary failure for patients undergoing axillary dissection (AXD) who were irradiated to the breast only was 2.1% (nine of 420) for patients with negative nodes and 2.1% (one of 47) for patients with one to three positive nodes. The incidence of supraclavicular failure in these two groups was 1.9% (eight of 420) and 0% (zero of 47), respectively. The incidences of axillary and supraclavicular failure in patients without clinically suspicious axillary involvement who did not have AXD but were treated with RT were 0.8% (three of 355) and 0.3% (one of 364), respectively. Despite various combinations of salvage surgery, RT, and systemic therapy, only 47% of patients (18 of 38) achieved complete regional control after nodal relapse. We conclude that RNF is uncommon in patients treated to the breast alone following an adequate AXD when the axillary nodes are negative or when one to three nodes are positive. RNF is also uncommon in patients with a clinically uninvolved axilla treated with nodal RT without AXD. Symptoms of RNF can be controlled in most but not all patients. Further study is needed to determine if the benefits of RT in preventing a small number of symptomatic RNF outweigh the potential toxicity for any subgroup of patients.

Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome.

The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities.

Are cosmetic results following conservative surgery and radiation therapy for early breast cancer dependent on technique

To assess the cosmetic results in relation to treatment technique, we retrospectively reviewed the results for 1159 Stage I-II breast cancer patients treated with conservative surgery and radiotherapy between 1970-1985. All patients underwent gross excision followed by radiation therapy including an implant or electron beam boost. The total dose to the primary site was greater than or equal to 60 Gy. Because of technical modifications introduced over time after 1981, the population was divided arbitrarily into two cohorts: 504 patients treated through 1981 and 655 treated between 1982-1985. Median follow-up time for surviving patients in the two cohorts were 107 months and 67 months, respectively. Cosmetic outcome was evaluated by the examining physician and scored as excellent, good, fair or poor. Excellent results at 5 years were scored in 59% of early cohort patients and 74% of the latter cohort (p = 0.002). Acceptable results (either good or excellent) were seen in 84% and 94%, respectively (p = 0.02). In the latter cohort, the likelihood of achieving an excellent result, but not an acceptable result, was significantly related to the volume of resected breast tissue and the use of chemotherapy. The number of fields (three-field technique, provided that fields are precisely matched, compared to tangents only) and boost type (implant vs electrons) did not influence the cosmetic outcome. We conclude that our current technique using breast RT to 45-46 Gy and a boost to the primary site of 16-18 Gy is associated with a high likelihood of acceptable cosmetic results and that this likelihood is not diminished by the use of adjuvant chemotherapy, a large breast resection, the use of a third field, or boost type.

The use of dose volume constraints to achieve rectal isotoxicity: A phase II prostate cancer radiation therapy dose escalation study

4628 Background: The primary limiting factor for prostate cancer irradiation is the risk of rectal toxicity. Rectal toxicity is associated with the dose and volume of the rectum irradiated. This dose escalation study has the unique feature of using dose volume histogram (DVH) constraints to determine the prescribed dose. METHODS From 1999-2002, 331 patients with clinical stage T1-T3N0M0 prostate cancer were prospectively treated with 3D conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed based on multiple CT scans. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined using a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: 1) <30% of the rectal wall volume can receive >75.6 Gy. 2) <5% of the rectal wall can receive >82 Gy. The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. Median follow-up was 1.6 years. RESULTS 34 patients (10%) experienced grade 2 chronic rectal toxicity (9% rectal bleeding, 6% proctitis, 3% diarrhea, 1% rectal pain) at a median interval of 1.1 years. Nine patients (3%) experienced grade ≥3 chronic rectal toxicity (1 grade 4) at a median interval of 1.2 years (table). The 3-year rates of grade ≥2 and grade ≥3 chronic rectal toxicity were 20% and 4%, respectively. There was no significant difference by dose level in the 2-year rate of grade ≥2 chronic rectal toxicity. These rates were 27%, 15%, 14%, 17% and 24% for the ≤72, 73.8, 75.6, 77.4, and 79.2 Gy dose level groups respectively (p = 0.27). CONCLUSIONS High dose levels (79.2 Gy) can be safely delivered if selected DVH constraints are met. The prescribed dose should be based on DVH information (toxicity risk) and the benefit of a specific dose level. [Figure: see text] No significant financial relationships to disclose.