Combined modality treatments are indicated for most patients with breast cancer. The definition of a proper treatment schedule and of the timing of each modality is a relevant issue that affects the ...feasibility and the clinical outcome of the treatment. A review of the literature was done on the timing of radiation therapy (RT) in the post-operative treatment of breast cancer. Retrospective studies and randomized clinical trials addressing the issue were considered and grouped according to the combined modality treatments performed. With regard to breast conserving surgery and adjuvant RT, it was verified that a delay up to 8 weeks between breast surgery and start of RT is not associated with an increased risk of local failure if compared with RT started within 4 weeks. Concerning breast conserving surgery followed by adjuvant RT and chemotherapy, the choice of the best schedule is still a complex unresolved issue. More results on sequential schedule of adjuvant RT and chemotherapy from recently published randomized studies are available. The reconstruction of the breast after conservative surgery is rarely necessary and is usually performed immediately after surgical treatment. With regard to mastectomy followed by adjuvant RT and breast reconstruction, it appears from some retrospective studies that autologous tissue transfer offers better results over implants. Concerning the transverse rectus abdominis muscle (TRAM) procedure, either immediate reconstruction before RT or delayed reconstruction after RT was feasible without significative differences in complication rates. Further randomized clinical studies are required to address the unresolved issues linked to the timing of RT. At present the treatment plan should be based on the patient's individual circumstances with regard to risk of metastasis and local failure.
In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., ...mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy.
A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy.
At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively.
The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.
Background. The efficacy and toxicity of total body irradiation (TBI) in patients with chronic lymphocytic leukemia (CLL) and low grade non‐Hodgkin's lymphomas (NHL) were evaluated.
Methods. Between ...January 1984 and September 1992, 81 consecutive patients, 40 affected with CLL and 41 with low grade NHL, with symptomatic Stage III and IV disease, were treated with TBI followed by prednimustine.
TBI was given with a 6 MV linear accelerator, applying two opposite alternating fields, including total body, with two fractions of 15 cGy given per week (3‐day interval). A total dose of 150 cGy was given over 5 weeks. Six to nine courses of prednimustine (100 mg/m2 orally for 5 consecutive days every 4 weeks) was administered 2 months after TBI treatment as consolidation therapy.
Results. Of 40 patients with CLL, 18 (Group I; median age 58.5 years) were younger than 65 years and 22 (Group II; median age 73 years) were older. The overall response rates were 78% in Group I and 91% in Group II, with a median response time of 16.5 and 16 months, respectively. Hematologic toxicity was 72% in Group I and 73% in Group II. It was reversible in all but one heavily pretreated patient who died of progressive anemia and thrombocytopenia after TBI alone. In the 40 patients with CLL, the response rate was 85%; there were 5 complete responses (CRs) (12.5%) and 29 partial responses (PRs) (72.5%).
Of the 41 patients with NHL, 29 (Group I; median age 55 years) were younger than 65 years and 12 (Group II; median age 71.5) were older. The overall response rate in both groups was 83%, with median response times of 18.5+ and 14.5+ months for Groups I and II, respectively. Hematologic toxicity was 59% in Group I, whereas it was 50% in Group II. It was reversible in all patients. Overall, in the 41 patients with symptomatic Stage III and IV low grade NHL, the response rate was 82.8%; there were 10 CRs (24.3%) and 24 PRs (58.5%).
The prednimustine regimen was generally well tolerated.
Conclusions. In our experience, TBI given in a dose of 150 cGy in 10 fractions twice a week, followed by prednimustine, is an effective treatment for patients with CLL and patients with low grade NHL. This treatment also is effective in patients older than 65 years. The toxicity is acceptable, particularly when TBI and prednimustine are given as initial treatment. Pretreated patients should be monitored strictly.
From January 1984 to December 1986, 94 patients with unresectable, locally advanced, non-small cell lung cancer (NSCLC) were treated to assess both the efficacy and the toxicity of a combined ...modality treatment including radiation therapy (45 Gy/15 fractions/3 weeks) and daily low dose cDDP (6 mg/m2). The overall response rate for the 90 evaluable patients was 54.3% with 16.6% of complete responses. At a minimum follow-up of 4 years, the overall median survival time was 12 months. Provided adequate hydration is ensured, the cDDP regimen chosen as a radiosensitizer can be safely combined with radiation therapy.
Anthracyclines are among the most active agents for the treatment of patients with locally advanced breast cancer. The aim of our study was to evaluate the feasibility and activity of a relatively ...high-dose regimen with 4-epirubicin plus normal doses of cyclophosphamide over a short period of time without the use of hematologic growth factors as adjuvant in resected locally advanced breast cancer.
Between January 1990 and June 1992, 43 consecutive patients, premenopausal or postmenopausal < 60 yrs, were surgically resected and then treated with epirubicin plus cyclophosphamide for at least 4 cycles (maximum 6). Electron beam (6-10 MeV energy) radiotherapy was delivered on the chest wall in patients with pathological skin infiltration (pT4b).
Median age was 46 years (range, 27-59); 37 were premenopausal and 6 postmenopausal. The total number of administered cycles was 202 (6 in 15 patients and 4 in 28 patients); 195/202 (96.5%) were administered at full dose, and 7 (3.5%) were reduced to 75% of the planned dosage. The three-year disease-free survival was 67% for stage IIIa and 61% for stage IIIb patients. The three-year overall survival was 88% and 79%, respectively. Local relapse only was reported in one patient (2%), distant relapse in 11 patients (25%), and local and distant relapse in four patients (9%). Toxicity was acceptable and mainly hematologic.
Our trial showed that the regimen is feasible without the use of hematologic growth factors. In this era of cost containment, the use of this short-term, high-dose induction course instead of repetitive courses of conventional dose regimens merits further evaluation, possibly in a large randomized trial.
The primary site remains unknown in 0.5-15% of patients with multiple metastases. In 5-20% of these patients bone metastases are the first sign of disease. Survival after diagnosis ranges 2 to 6 ...months and 1-year survival is less than 25%. First of all, this paper reviews the current diagnostic and therapeutic approaches to patients with bone metastases from an unknown primary site and then reports the 10-year experience with radiotherapy at the Radiotherapy Division of the Centro di Riferimento Oncologico (Aviano) and of the Pordenone General Hospital in this patient population. Seventy-nine patients with bone metastases were evaluated. In 33 patients histology confirmed the original diagnosis and in 46 patients diagnosis was based on radiological and clinical findings. With respect to pain relief, differences in irradiated areas and in the ages of the patients were not significant. The patient's sex, however, did make a difference both to the degree of pain relief achieved and to survival (more favorable in women). To conclude, this paper suggests the diagnostic procedures necessary for the correct follow-up of patients with bone metastases from an unknown primary site.
A group of 38 patients with a median age of 70 years and chronic lymphocytic leukemia (CLL) were treated using a cobalt 60 U or a 6‐MeV linear accelerator. A direct field or two opposite fields ...covered the palpable spleen area in most patients. 100 cGy were administered weekly for a total dose of 10 Gy, given over 10 weeks. The stage arrangement (according to Rai) for the 32 evaluable patients was as follows: Stage I: 11 patients, Stage II: nine patients, Stage III: three patients, and Stage IV: nine patients. Patients in Stages I and II were treated when symptomatic. Twenty‐five patients (78%) achieved hematologic response (HR), defined as normalization of the differential leukocyte count, of the total blood cell count, and of bone marrow infiltration. However, no complete response according to the standard criteria of response has been obtained. The median response time of HR was 7 months (range, 1.5 months to > 120 months). The overall median survival time from the start of splenic irradiation (SI) was 40 months. More than 50% splenomegaly reduction was obtained in 63% of patients, whereas no benefit was verified in the lymphadenopathy. The incidence of second tumor was 29%. Fourteen patients benefited from a further 21 SI cycles. SI does not result in a complete remission and threfore cannot modify the course of CLL. This treatment is most advisable for elderly patients with predominant bone marrow lymphocytosis, for patients with previous extensive chemotherapy or radiotherapy, and for patients with poor marrow reserve. Moreover, because of the absence of toxicity subsequent treatment is not compromised.
From April 1983 through December 1989, 42 consecutive patients with diagnosis of epithelial ovarian carcinoma were initially managed by aggressive surgery and three courses of endoperitoneal ...cis-platinum-based chemotherapy followed by an alternating combination chemotherapy and second-look laparotomy. Patients with residual tumor less than or equal to 2 cm subsequently received whole abdominal radiation therapy (WAR). Twenty-eight patients (42% with no residual disease, 21% with microscopic disease, and 36% with residual disease less than 2 cm) were eligible for WAR. WAR was delivered using an open-field technique up to 22 Gy in 20 fractions followed by a pelvic boost of 18 Gy in 10 fractions. The kidneys were shielded posteriorly at 1100 cGy; hepatic shields were not added. One patient did not complete WAR for lung metastases after 5 radiotherapy fractions. The complete treatment program lasted 8 months (range, 6.8-11). The median follow-up of the 28 patients entered into the study was 50 months. Eight patients are alive and disease-free at 5 years. The overall and disease-free survival rates at 5 years are 45 and 30%, respectively. All but 2 patients relapsed within the abdominopelvic cavity and 3 developed brain metastases. Toxic effects, during WAR, required treatment interruption in all but 4 patients: 3 developed a small bowel obstruction requiring surgery and 1 died of surgical complications in complete remission. The poor disease-free survival and the severe toxicity encountered have been valid indications that WAR should be discontinued as a treatment modality in advanced ovarian cancer at our department.
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