Roberto Zucali

Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy.

In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkins disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy.

A Randomized Trial Comparing Axillary Dissection to No Axillary Dissection in Older Patients With T1N0 Breast Cancer: Results After 5 Years of Follow-up

Summary Background Data:Axillary dissection, an invasive procedure that may adversely affect quality of life, used to obtain prognostic information in breast cancer, is being supplanted by sentinel node biopsy. In older women with early breast cancer and no palpable axillary nodes, it may be safe to give no axillary treatment. We addressed this issue in a randomized trial comparing axillary dissection with no axillary dissection in older patients with T1N0 breast cancer. Methods:From 1996 to 2000, 219 women, 65 to 80 years of age, with early breast cancer and clinically negative axillary nodes were randomized to conservative breast surgery with or without axillary dissection. Tamoxifen was prescribed to all patients for 5 years. The primary endpoints were axillary events in the no axillary dissection arm, comparison of overall mortality (by log rank test), breast cancer mortality, and breast events (by Gray test). Results:Considering a follow-up of 60 months, there were no significant differences in overall or breast cancer mortality, or crude cumulative incidence of breast events, between the 2 groups. Only 2 patients in the no axillary dissection arm (8 and 40 months after surgery) developed overt axillary involvement during follow-up. Conclusions:Older patients with T1N0 breast cancer can be treated by conservative breast surgery and no axillary dissection without adversely affecting breast cancer mortality or overall survival. The very low cumulative incidence of axillary events suggests that even sentinel node biopsy is unnecessary in these patients. Axillary dissection should be reserved for the small proportion of patients who later develop overt axillary disease.

Prognostic factors in locally advanced noninflammatory breast cancer. Long-term results following primary chemotherapy

Since 1973 we have treated T3b-T4 (stage III) breast cancer with various forms of multidisciplinary approaches through prospective trials. The present report analyses the 10-year results of 277 patients. Primary chemotherapy consisted of adriamycin plus vincristine given for three or four cycles prior to high-energy irradiation or surgery. In 205 of 277 (74%) additional chemotherapy was planned following the local-regional modality. Primary chemotherapy yielded complete plus partial remission in 62% (CR 7%). Long-term freedom from progression and overall survival were significantly improved by the addition of chemotherapy following local-regional treatment (radiotherapy or surgery). Further chemotherapy was able to significantly affect treatment outcome when it was analyzed both singly and in the presence of other prognostic variables. Thus, in our experience, the variables significantly affecting the 10-year results were represented by duration of treatment and tumor cell burden expressed by size of primary malignancy and clinical nodal status. Locally advanced breast cancer appears a pleomorphic disease difficult to control over a long period of time because of its frequent presentation with bulky tumor and the very high risk of disseminated micrometastases. Thus, the management of this stage of disease almost invariably requires a multidisciplinary approach.

Early breast cancer: evaluation of the prognostic role of the site of the primary tumor.

PURPOSE 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. PATIENTS AND METHODS 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%). RESULTS 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. CONCLUSION 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.

Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer

At Istituto Tumori of Milano in a series of 3295 patients treated with conservative surgery and radiotherapy for breast cancer from 1973 to 1989 three cases of soft tissue sarcoma were observed in irradiated breasts. One patient developed a fibrosarcoma of the breast stroma, 16 months after irradiation. A grade II bulky angiosarcoma was diagnosed in the breast of a patient treated 59 months previously. The third was a grade II angiosarcoma detected 41 months after therapy. At present, the risk of a second primary in the irradiated breast seems too low to justify modification of our present policy of conservative therapy of breast cancer, but a careful and longer follow-up is needed.

Combined preoperative chemoradiotherapy followed by radical surgery in locally advanced vulvar carcinoma: A pilot study

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 chemoradiotherapy followed by radical surgery for patients with locally advanced squamous cell carcinoma of the vulva.

Nutritional support in patients with cancer of the esophagus: Impact on nutritional status, patient compliance to therapy, and survival

Aims and background The multimodal approach to patients with esophageal squamous cell carcinoma often includes poly-chemotherapy combined with radiation therapy. Cancer dysphagia and drug-related anorexia, mucositis and vomiting can all lead to malnutrition. The aim of this study was to analyze the impact of the administration of enteral nutrition (EN) on the patients nutritional status, tolerance of chemotherapy and radiotherapy, and final oncological outcome. Methods Fifty esophageal cancer patients who were to be submitted to chemotherapy (days 1-4 5-fluorouracil (FU) 1 g/m2/day and cisplatin (CDDP) 100 mg/m2/day 1) for two cycles plus radiotherapy (31 Gy) were referred to the Nutrition Support Unit prior to any therapy due to their malnourished status. Twenty-nine dysphagic patients received nutrition via tube (37 kcal/kg/day + 2.0 g proteins/kg/day for 34 days), while 21 others who were not dysphagic were given a standard oral diet (SD). The patients who received EN had a more severe weight loss than the SD patients (16.8% vs 12.8%, P <0.02). Results The dose of administered EN represented 86% of the planned support, and 70% of the nutritional therapy was administered in the home setting. Administration of EN support resulted in stable body weight and unchanged levels of visceral proteins, while SD patients had a decrease in body weight, total proteins and serum albumin (P <0.01). There was no difference between the two groups in terms of tolerance and response to cancer therapy, suitability for radical resection and median survival (9.5 months). Conclusions EN in patients with cancer of the esophagus undergoing chemotherapy and radiotherapy is well tolerated, feasible even in the home setting, prevents further nutritional deterioration and achieves the same oncological results in dysphagic patients as those achieved in non-dysphagic patients.

Prognostic factors for metachronous contralateral breast cancer: A comparison of the linear Cox regression model and its artificial neural network extension

The purpose of the present study was toassess prognostic factors for metachronous contralateral recurrence ofbreast cancer (CBC). Two factors were of particularinterest, namely estrogen (ER) and progesterone (PgR) receptorsassayed with the biochemical method in primary tumortissue. Information was obtained from a prospective clinicaldatabase for 1763 axillary node-negative women who hadreceived curative surgery, mostly of the conservative type,and followed-up for a median of 82 months.The analysis was performed based on both astandard (linear) Cox model and an artificial neuralnetwork (ANN) extension of this model proposed byFaraggi and Simon [9]. Furthermore, to assess theprognostic importance of the factors considered, model predictiveability was computed.In agreement with already published studies, the resultsof our analysis confirmed the prognostic role ofage at surgery, histology, and primary tumor site,in that young patients (≤ 45 years) withtumors of lobular histology or located at inner/centralmammary quadrants were at greater risk of developingCBC. ER and PgR were also shown tohave a prognostic role. Their effect, however, wasnot simple in relation to the presence ofinteractions between ER and age, and between PgRand histology. In fact, ER appeared to playa protective role in young patients, whereas theopposite was true in older women. Higher levelsof PgR implied a greater hazard of CBCoccurrence in infiltrating duct carcinoma or tumors withan associated extensive intraductal component, and a lowerhazard in infiltrating lobular carcinoma or other histotypes.In spite of the above findings, the predictivevalue of both the standard and ANN Coxmodels was relatively low, thus suggesting an intrinsiclimitation of the prognostic variables considered, rather thantheir suboptimal modeling. Research for better prognostic variablesshould therefore continue.

Preoperative radiation therapy for patients with T2–T3 carcinoma of the middle-to-lower rectum

The aim of this study was to determine the effects of preoperative radiation therapy (RT) on the objective responses of patients with rectal carcinoma to their treatment. These effects were assessed with endorectal ultrasound (EUS) evaluation, histopathologic grading of postirradiation tumor mass reduction in the surgical specimen, and analysis of local and distant recurrences.

New perspective in the treatment of low rectal cancer: Total rectal resection and coloendoanal anastomosis

PURPOSE: Presently abdominoperineal resection still remains the most diffuse modality of treatment of low rectal cancer. However, a new surgical approach is now available to avoid such a demolitive surgery and a definitive colostomy. METHODS: From March 1990 to March 1993, 58 total rectal resections were performed in 55 patients affected with primary or recurring cancers of the low rectum. As a restorative procedure, a colic J-shaped pouch and a handsewn pouch-endoanal anastomosis was adopted. All of the primary lesions were within 7 cm of the anal verge; in 74 percent the distal tumor margin was located less than 6 cm from the cutaneous edge. RESULTS: Histologic clearance of the rectum cut edge was documented in all cases. Seven patients relapsed locally from 7 to 14 months after surgery and in 3 more cases distant metastases were documented. Postoperative morbidity is low. After colostomy closure in 78 percent of patients, perfect continence was achieved and in 74 percent less than two bowel movements a day were recorded. Fifty patients are presently alive, 46 without evidence of disease. The follow-up ranged from 2 to 37 (median, 13) months. CONCLUSION: This experience, along with data obtained from last years literature, indicates that a conservative surgical procedure, such as total rectal resection and coloendoanal anastomosis, can be considered a feasible and radical option for treatment of low rectal cancer.