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ABSTRACT: The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data.
Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%).
Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors.
Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.
Journal of Clinical Oncology 04/1998; 16(4):1363-6. · 18.37 Impact Factor
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ABSTRACT: Brachytherapy is widely adopted as an exclusive treatment of T1/T2 oral cancer with a high probability of definitive cure. Therefore, any major complication, like mandibular bone necrosis, should be avoided. Many risk factors, either clinical or technical, have been considered in the literature.
One hundred consecutive interstitial iridium LDR treatments for early cancers of the tongue and floor of the mouth performed from January 1989 to November 1993 were reviewed. An analysis of some simple technical parameters (total dose, dose-rate, reference volume, linear activity, total reference kerma) was performed in order to identify the main physical risk factors. Moreover, total dose was recalculated as extrapolated responsive dose for normal tissue complications.
Bone necrosis was observed in 10 out of 100 patients with a median follow-up of 38 months. No significant incidence of this complication was observed when tumor site (mobile tongue versus floor of the mouth), dental status or total physical dose were considered. A significant correlation between the incidence of bone necrosis and two main parameters was found, i.e. dose-rate (P < 0.02) and reference volume (P < 0.05).
A threshold value may be suggested both for dose-rate (50 cGy/h) and reference volume (25,000 mm3). Bone necrosis is clearly related to both these parameters since most cases (i.e. 80%) were observed in the subgroup over the volume and dose-rate threshold.
Radiotherapy and Oncology 08/1997; 44(2):143-7. · 5.58 Impact Factor
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ABSTRACT: In clinical breast cancer research, the utility of certain biomarkers as predictors of response to surgery, chemotherapy, or hormonal therapy has been studied intensively. Much less research has been done on the relevance of biologic predictors of response to radiotherapy, which represents an effective local-regional treatment for breast cancer.
The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients. These patients had had no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in distant sites and had had similar distributions of clinicopathologic and biologic prognostic features. They had been treated by conservative surgery alone (139 case patients) or by conservative surgery followed by adjuvant radiotherapy (496 case patients) during the period from 1984 through 1990.
The expression of the p53, GST-pi, and Bcl-2 proteins in the specimens of primary breast tumor obtained from these patients was determined by use of immunohistochemistry; cell proliferation activity and levels of steroid receptors were determined by use of a [3H]thymidine-labeling index assay and the dextran-coated charcoal technique, respectively. The median time of follow-up of patients was 6 years. In the analyses of patient outcomes, only local failures that presented as first events were considered.
After surgery alone, the risk of local recurrence at 6 years was higher for patients with tumors exhibiting elevated levels of p53 and GST-pi protein expression than for patients with low levels (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of Bcl-2 protein was only suggestive of a higher frequency of local failures. Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor status did not change these findings. Conversely, in the series of patients given conservative surgery followed by radiotherapy, there was no difference in local tumor recurrence between patients with tumors expressing or not expressing each of the three markers.
Our study provides indirect evidence of a benefit from radiation therapy in preventing local breast cancer relapse, particularly among node-negative patients with tumors that express elevated levels of the p53 or GST-pi proteins or that express little or no Bcl-2 protein.
JNCI Journal of the National Cancer Institute 06/1997; 89(9):639-45. · 13.76 Impact Factor
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ABSTRACT: This prospective phase II study was designed to test the activity and toxicity of a regimen of fluorouracil (5-FU) and cisplatin (CDDP) in combination with radiation therapy in the treatment of epidermoid cancer of the anal canal.
Thirty-five consecutive patients with untreated epidermoid cancer of the anal canal were candidates for chemoradiation therapy (CRT). Staging of cancer was as follows: T1, 26%; T2, 60%; T3, 14%; and N1, 2,3, 26%. No patient had distant metastases. The treatment protocol consisted of two to three cycles of chemotherapy starting on days 1 and 21 and concurrent radiotherapy at a daily dose of 1.8 Gy up to a total dose of 36 to 38 Gy in 4 weeks, delivered to the anal region, perineum, middle and lower pelvis, and inguinal and external iliac nodes. Radiotherapy was then delivered to the anoperineal region and metastatic inguinal nodes to a total dose of 18 to 24 Gy in 10 fractions. Chemotherapy consisted of 24-hour intravenous (IV) infusion of 5-FU 750 mg/m2 on days 1 to 4 and CDDP 100 mg/m2 by 60-minute IV infusion on day 1.
All patients received two cycles of chemotherapy; the second was delayed in three patients because of leukopenia that was evident in 11 (31%). In eight patients, a third cycle was added. They all experienced nausea or vomiting; one patient showed signs of cardiotoxicity and one developed proctitis, dermatitis, and diarrhea (grade 3). Complete regression (CR) was assessed in 33 patients (94%); nine patients with metastatic lymph nodes also had CR. Two patients had a partial response (PR); both underwent abdominoperineal resection, which was not curative in one. Two patients (6%) had a local recurrence; in one, this was associated with hepatic metastases. One of these patients underwent surgery and is alive after about 4 years, while the other is undergoing chemotherapy. After a median follow-up duration of 37 months, 94% of patients are alive without evidence of disease and 86% are colostomy-free.
This regimen is well tolerated; its toxicity does not exceed that observed with the combination of 5-FU and mitomycin (MMC). Compared with our previous experience based on the classic CRT (5-FU, MMC, and radiation), the objective response rate observed with this new combination was similar. However, the local recurrence rate, observed in patients treated with the new regimen, was lower (6% v 24%). According to more recent data from the literature, primary CRT is the elective indication in epidermoid cancer of the anus and replacement of MMC with CDDP seems an effective and logical evolution.
Journal of Clinical Oncology 01/1997; 14(12):3121-5. · 18.37 Impact Factor
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ABSTRACT: Although for decades exenterative surgery has represented the standard treatment for patients with locally advanced vulvar cancer, combined approaches, including preoperative radiation with or without chemotherapy, are now considered the treatment of choice. We report the results of a pilot study on concurrent chemoradiotheraphy followed by radical surgery for patients with locally advanced squamous cell carcinomas of the vulva.
Thirty-one patients with squamous cell carcinoma of the vulva were treated with two courses of combination chemotherapy mitomycin C, 15 mg/m2 intravenously (i.v.) on Day 1, and 5-fluorouracil, 750 mg/m2 i.v., in continuous 24-hour infusion on Days 1 to 5. Inguinal and pelvic lymph node chains and the vulva were irradiated (starting on the same day as the chemotherapy) up to a total dose of 36 Gy. After a 2-week interval, a second course of chemoradiotherapy was given (18 Gy on the vulvar region only). After 2 weeks, patients underwent radical surgery.
An objective response was observed in 22 of 24 primary cases (91.6%) and in 7 of 7 recurrent cases. All but two unresponsive patients underwent radical surgery. The postoperative morbidity rate was 65% (19 of 29 patients), and the mortality rate was 13.8% (4 of 29 patients). Five of nine patients (55%) with biopsy-proven inguinal lymph node metastases showed no residual lymph node disease in the surgical specimen. The recurrence rate was 31.8% and the medial follow-up time was 34 months.
Chemoradiotherapy seems to be effective for squamous cell carcinoma of the vulva. If treatment-related morbidity could be decreased, such a combined approach might offer a new perspectives for a conservative treatment of locally advanced vulvar cancer.
Cancer 05/1996; 77(8):1472-8. · 4.77 Impact Factor
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ABSTRACT: A series of 191 patients submitted to adjuvant radiotherapy after surgery for rectal and rectosigmoid carcinoma from January, 1975, to December, 1990, has been analyzed to evaluate the incidence of high grade small bowel late toxicity (grades III/IV according to RTOG/EORTC scoring system). Surgical approach was abdominoperineal Miles resection in 92 patients, while a sphincter preserving bowel resection was performed in 99. The total radiation dose to the pelvis ranged from 40 to 60 Gy in 4 to 8 weeks, with conventional fractionation. Three different beams arrangements were used: two sagittal parallel opposite AP-PA fields in 106 patients, three fields (one posterior sagittal plus two parallel lateral fields) in 56, four fields (box technique) in 29. Fourteen patients (7.3%) developed sequelae grades III/IV: three of them died of toxicity. Average free interval between radiation and complication was 23 months (range: 4-87). The following risk factors were investigated: sex, age, type of surgery on primary rectosigmoid cancer, previous abdominal or pelvic surgery, radiation technique, treated volume, administered radiation dose. Dose was calculated as BED (time corrected biologically equivalent dose) according to the linear quadratic model. The only factors significantly related to late intestinal complications were the beam arrangement and, consequently, the treated volume. Detailed analysis showed that radiation sequelae developed in 12/106 (11.3%) patients treated with the two sagittal fields technique, while small bowel toxicity was observed in only 2/85 (2.3%) patients treated with the three--or four--fields technique. The difference is stastically significant (p < 0.05). Another significant correlation was the ratio between treated volume and late complications incidence observed.(ABSTRACT TRUNCATED AT 250 WORDS)
La radiologia medica 06/1995; 89(5):643-6. · 1.44 Impact Factor
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ABSTRACT: Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.
Gynecologic Oncology 12/1992; 47(2):239-46. · 3.89 Impact Factor
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ABSTRACT: The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.
International Journal of Radiation OncologyBiologyPhysics 07/1987; 13(6):853-60. · 4.11 Impact Factor
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ABSTRACT: From 1974 to 1982 a total of 58 patients with locoregional breast cancer, judged not suitable for demolitive surgery because of old age, bad general conditions or other reasons, were treated with simple tumorectomy followed by radiotherapy. The median age of the patients was 71 years. Two patients had synchronous bilateral breast cancer, both treated with the same conservative approach. Thirty-three tumors were classified as T1, 24 as T2, 1 as T3, and 2 as T4 of a small size. The median size of the tumor was 2 cm; mean size was 2.24 cm. Radiotherapy was given to the whole breast, followed by a conedown on the tumor bed. The median dose to the tumor bed was 64 Gy, over 7-9 weeks. Thirty-two patients received irradiation on nodal sites too, up to 45-60 Gy. The median follow-up for the whole series was 44 months. Only 4 of 60 treated breasts have presented a local recurrence (6.6%); relapse-free survival at 3 and 5 years is 85.4% and 79%, respectively. Our results confirm that tumorectomy followed by radiotherapy appears to be a very effective alternative to radiotherapy alone and to demolitive surgery. In fact, local control, survival and cosmetic results are quite satisfactory and achievable through a simple therapeutic modality.
Tumori 01/1986; 71(6):571-4. · 0.86 Impact Factor
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G De Palo,
S Pilotti, R Kenda,
E Ratti,
R Musumeci,
C Mangioni,
F Di Re,
A Lattuada,
U Conti,
F Cefis,
L Recanatini,
S Carinelli,
G Rossi
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ABSTRACT: Data on 56 patients with pure dysgerminoma are discussed. Forty-nine patients were classified as having new disease or were to have reassessment of disease, and seven cases were to be restaged (one with and six without clinical evidence of disease). Of new and reassessment cases, 44 patients underwent lymphography, 16 underwent peritoneoscopy with diaphragmatic inspection and 30 had peritoneal cytologic testing performed. Positive lymphography resulted in restaging in 31.6% of patients. Diaphragmatic inspection was always negative. Peritoneal cytologic testing was positive for malignant cells in three patients and worsened the stage in one. Pathologic staging of disease was as follows: Stage IA, 24; Stage IB, one Stage IC, one; Stage III peritoneal disease, two. Stage III retroperitoneal disease, 12; Stage III peritoneal and retroperitoneal disease; four. The 5-year relapse-free survival rates were 91% in patients with pathologic Stages IA, IB, and IC; 74% in those with Stage III retroperitoneal disease, and 24% in patients with Stage III peritoneal disease or peritoneal plus retroperitoneal disease. The results indicate that the prognosis is excellent for patients with Stage I and Stage III retroperitoneal disease whereas peritoneal involvement is associated with a poor prognosis.
American Journal of Obstetrics and Gynecology 09/1982; 143(7):799-807. · 3.47 Impact Factor
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Tumori 09/1982; 68(4):341-7. · 0.86 Impact Factor
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ABSTRACT: From 1969 to 1977, 420 patients with endometrial carcinoma were observed and treated at the National Tumor Institute of Milan. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed in 351. After careful clinical and pathologic review, 262 patients were classified as having stage I disease. Further treatment included post-operative radium therapy to the vaginal vault. There were 247 cases with adenocarcinoma, 10 with adenoacanthoma, and 5 with adenosquamous or clear cell carcinoma. Of 257 cases with adenocarcinoma or adenoacanthoma, 63 were grade 1, 161 grade 2, and 33 grade 3. Of the total series, only 41 cases had disease limited to the mucosal surface. The 5-year actuarial survival was 91.4% and the recurrence-free survival was 93.4%. The case material was evaluated according to the risk factors, and results were 1) premenopausal patients had a better prognosis (100% recurrence-free survival versus 92.8% for postmenopausal women, P = .003); 2) length of the uterine cavity was not a significant prognostic factor; 3) myometrial invasion alone was not prognostic but correlated with grade of tumor; 4) the grade of the tumor was an important determinant of recurrence (grade 1 98% recurrence-free survival, grade 2 95%, grade 3 79%). With the described therapy, vaginal recurrences were absent. The recurrences were distant in 20% and local with or without distant metastases in 80%.
Obstetrics and Gynecology 09/1982; 60(2):225-31. · 4.73 Impact Factor
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ABSTRACT: The clinical and pathologic features of 34 uterine sarcomas were studied to determine the natural history of the disease. Sixteen patients had leiomyosarcoma, five mixed mesodermal sarcoma, ten endometrial stromal sarcoma, two carcinosarcoma and one endolymphatic stromal myosis. The patients were treated without an unique protocol. At 3 years the actuarial relapse-free survival was 53.6%: 68.4% in stage I-II patients and 22.2% in stage III-IV patients. As regards the histologic subtype mixed mesodermal sarcomas had the best prognosis; endometrial stromal sarcomas the worst. The necessity of a uniform clinical and histologic classification as well as the importance of controlled clinical trials are pointed out.
Tumori 09/1981; 67(4):341-8. · 0.86 Impact Factor
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Gynecologic Oncology 03/1981; 11(1):17-22. · 3.89 Impact Factor
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ABSTRACT: Sixty-four patients, 34 with no clinical evidence of disease (NED) and 30 with clinical evidence of disease (ED), were submitted to restaging with peritoneoscopy plus diaphragmatic inspection, peritoneal cytology, and lymphography. Eleven patients (32.2%) in the NED group and 25 (83.3%) in the ED group had positive restaging findings. The 3 diagnostic procedures, in combination, are important in establishing occult disease and therefore in the planning of further treatment.
Obstetrics and Gynecology 02/1981; 57(1):96-8. · 4.73 Impact Factor
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European journal of gynaecological oncology 01/1981; 1(3):140-5. · 0.47 Impact Factor
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European Journal of Cancer (1965) 12/1980; 16(11):1469-74.
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ABSTRACT: The results of foot lymphography in 295 patients with endometrial carcinoma observed from 1968 to 1978 at two institutions are reported. One hundred and eighty-two were new cases, 61 were recurrences, and 52 were patients who underwent restaging diagnostic procedures without clinical evidence of disease. The incidence of lymphatic spread was correlated with the clinical stage, the pathologic stage, and the extent of recurrent disease. In fact, in the 182 new cases, at clinical stage, the pathologic stage, lymphography was positive in 8.9% of patients at Stage I, 28.6% at Stage II, 57.1% at Stage III, and 66.6% at Stage IV disease; at pathological stage, lymphography was positive in 8% of patients at Stage I, 14.8% at Stage II, 39.3% at Stage II, and 53.3% at Stage IV disease. There was lymph node involvement in 47.5% of the 61 pretreated patients. Finally, in 52 pretreated patients with no evidence of disease, the incidence of lymph node involvement was 7.7%. In new cases, metastases were found only in the pelvic nodes in 56.2% of the patients and only in the para-aortic nodes in 9.5%; in 34.3%, both chains were simultaneously involved. The five-year survival rate for patients at Stage I, II, and III disease with positive lymphography was 35% as compared with 73% for negative cases. In patients at Stage I and II, the difference of survival was equal to 24%. The reliability of the results is confirmed by the concordance with the data of the literature on histologic involvement, by the first radiologic-pathologic comparison, and by the clinical course of the positive cases. Lymphography is of unquestionable value for an appropriate staging and for a correct plan of treatment.
Cancer 11/1980; 46(8):1887-92. · 4.77 Impact Factor
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ABSTRACT: From 1973 through 1978, 365 patients with ovarian carcinoma were evaluated with lymphography. The extent of disease was assessed by clinical and conventional radiologic examinations, peritoneoscopy with visualization of diaphragmatic leaves, peritoneal cytology, and, in some patients, exploratory laparotomy. The highest incidence of metastases was found in advanced stages (31.1% in stage III and 60% in stage IV) and in recurrences (75.9%). In 87 patients with early disease, the incidence was 9.2%. In 36 pretreated patients with no evidence of disease, this incidence was 11.1%. Biopsies of the nodes were performed in 96 patients: radiologic accuracy was confirmed in 33 of 33 positive and in 55 of 63 negative cases. Of the patients, 33% had metastases only in the pelvic nodes, and 7.9% only in the paraaortic nodes; in 79.1%, both chains were involved simultaneously. These data confirm the importance of lymphography in diagnosis, treatment planning, and surveillance of ovarian carcinoma.
American Journal of Roentgenology 04/1980; 134(3):449-52. · 2.78 Impact Factor
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ABSTRACT: Ninety-four patients with T2 NO, N1a, N1b, MO were treated with primary radiotherapy (RT) because of old age or poor general conditions. In 32 patients (34%), younger in age and in better general conditions, Halsted radical mastectomy could be performed 5-8 months from starting RT; surgery was not done at random, but decided case by case on the basis of a good response to RT and an improvement of general status. Relapse was documented in 42 patients. Relapse rate was 50% in the group treated with RT alone (high incidence of breast recurrences) and 33% in the group operated on after RT. Distant metastases had the same incidence in the 2 groups, with a median free interval of 14 months. Overall disease-free survival rates at 5 to 10 years were 46% and 35%, respectively; these results are not particularly different from the data of historical series of T2 breast cancer treated with surgery alone. The patients operated on after RT had a significantly better survival, but the results were clearly influenced by the selection of patients. For the future, a safe policy could be a conservative combined treatment consisting of tumorectomy followed by curative RT; adjuvant medical therapy could be scheduled for high-risk patients (N1b).
Tumori 03/1980; 66(1):93-100. · 0.86 Impact Factor
