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By means of a questionnaire sent to Portuguese hospitals which diagnose and treat most female patients with breast cancer, it was intended to assess the situation regarding the treatment of carcinoma in situ and early breast cancer (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The hospital participation rate was 65% and a sample of 865 patients was collected, distributed by the years 1985, 1990, 1995 and 2000. It was observed that, in terms of surgery, there was an increase in conservative surgery, which was over 40% in 2000, as well as an increase in the average of excised axillary lymph nodes. Progress in the surgical approach was similar both in cancer centres and in large and university hospitals, when compared with the other surveyed hospitals. Also, no differences between these two hospital groups in disease-free survival and overall survival were found. Postoperative radiotherapy was employed in more than 90% of the patients submitted to conservative surgery and adjuvant chemotherapy was used in 39% of all the patients, while tamoxifen as adjuvant treatment was used in 58% of the patients.

The North Trent Cancer Network Breast Group in the United Kingdom revised its adjuvant treatment guidelines in breast cancer management in 1998. We aimed to check the compliance to the guidelines, 8 months after their introduction. Data were collected, retrospectively, from the medical records of patients with invasive breast cancer who underwent definitive surgery (in a 3-month period) in different cancer units and the cancer centre within the North Trent Cancer Network. The overall compliance to treatment guidelines was 82% (90% and 74% for chemotherapy and radiotherapy, respectively), which was similar across the network. In 5% of cases, compliance could not be determined. On case review, 22% of the non-compliant incidents were justified and 16% seemed to be due to variation in guideline interpretation. We discuss the possible reasons for non-compliance and show a need to periodically monitor compliance to adjuvant treatment guidelines.

The rationale for combining surgery, radiotherapy and chemotherapy is discussed and the clinical results seen with surgery and adjuvant radiochemotherapy in three major abdominal malignancies are reviewed. A systematic approach to the literature was used. In rectal cancer, postoperative radiochemotherapy is an established treatment, although there is weak scientific support for the combined approach. The same clinical gains can also be reached much more easily with preoperative radiotherapy. In gastric cancer, a recent large randomised trial showed improved survival from postoperative radiotherapy. This was not seen in a comparably large trial in pancreatic cancer. The reasons for the different results according to primary tumour site are discussed. It is argued that adequate coverage of all adjacent regional lymph node stations is necessary for an effect on survival., (Copyright 2003 S. Karger AG, Basel)

The international conference of adjuvant therapy for primary breast cancer in St. Gallen and the National Institute of Health Consensus Conference for Breast Cancer Treatment have recommended appropriate treatment for individual subgroups by recurrence risk. However, evidence provided by Japanese clinical trials did not contribute to the consensus recommendations. To compare the risk of recurrence in breast cancer patients between Japan and western countries, a database of Japanese breast cancer patients was analyzed. From 1991 to 2001, approximately 12100 articles listed on MEDLINE were reviewed by abstract, and articles were then selected and reviewed by the authors. According to the AHPC (Agency for Health Care Policy and Research), quality assessment and strength for recommendation of the evidence from clinical trials were classified. Even though there are likely some unknown ethnic differences, we should provide Japanese patients with state of the art treatment for breast cancer in accordance with global standard therapies, which have been evaluated by breast cancer specialists in western countries.

Radiation therapy will be used much more commonly in the treatment of adenocarcinoma of the stomach because of the results of the Intergroup Trial demonstrating an advantage to adjuvant postoperative chemoradiation therapy. Previous descriptions of radiation fields have not emphasized the variation in local spread patterns between tumors located in different portions of the stomach and the varying extent of the primary tumor and lymph node spread. Based on data obtained from surgical and pathologic series, we have recommended a variation in the radiation fields from those routinely applied at the present time. Tumors located primarily in the region of the gastric cardia have the highest risk of nodal involvement in the pericardial region and along the lesser and greater curvature, as well as risk of spread into the periesophageal tissue. However, there is a lower risk of involvement in the distally located nodes, especially in the gastric antrum, periduodenal, and porta hepatis regions. For a patient who has been well evaluated both surgically and pathologically, and found to be node negative, it may not be necessary to treat the nodes in these lower risk sites. Similarly, tumors that originate in the distal stomach, in the region of the gastric antrum, have a high likelihood of spread to the periduodenal, peripancreatic, and porta hepatis nodes, and a lower likelihood of spread to the nodes near the cardia of the stomach, the periesophageal and mediastinal nodes, or to the splenic hilar nodes. Any tumor originating in the stomach has a high propensity of spread to nodes along the greater and lesser curvature, although they are most likely to spread to those sites in close anatomic proximity to the primary tumor mass. Based on such information, we have described the nodal and primary sites that should be treated for different T- and N-stage tumors located in the cardia, body, or antrum of the stomach. These should be used as guides for defining appropriate field arrangements for the adjuvant postoperative therapy of gastric cancer., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Interest in platinum compounds for the treatment of breast cancer has been reawakened because of preclinical studies indicating synergy of platinum salts with the monoclonal antibody trastuzumab in human breast cancer cell lines that overexpress HER2/neu. Cisplatin, carboplatin, and iproplatin are not very active as single agents in patients with previously treated metastatic breast cancer (MBC). The activity of oxaliplatin has not been adequately tested in refractory MBC. On the other hand, cisplatin is very active as first-line chemotherapy, with response rates (RR) of 50%; carboplatin appears to be moderately active in patients without prior chemotherapy (RR around 30%). The clinical effectiveness of the other platinum compounds (iproplatin, oxaliplatin, and others) has not yet been fully tested as first-line chemotherapy. Platinum compounds have been extensively tested in combination with other antitumoral agents. Cisplatin combinations have been employed as neoadjuvant chemotherapy in women with locally advanced breast cancer. These combinations are very active, although the precise contribution of cisplatin to the overall activity is not known. Combinations with cisplatin have been investigated, essentially, as salvage therapy for patients with previously treated MBC. The combinations of cisplatin with older pharmacological agents (5-fluorouracil, etoposide) have moderate activity, while the combinations of cisplatin with the newer agents (vinorelbine, paclitaxel, docetaxel, gemcitabine) appear to be more active. The combinations of carboplatin with the classical agents (5-fluorouracil, etoposide) are poorly active in previously treated MBC; however, the combination of carboplatin with the taxanes (docetaxel, paclitaxel) is more active. Of greatest interest is the synergy between the platinum derivatives and the monoclonal antibody trastuzumab demonstrated in vitro in breast cancer cell lines overexpressing HER2/neu. Currently, several combinations of platinum compounds (either cisplatin or carboplatin) with docetaxel and trastuzumab are under clinical testing in patients with MBC who overexpress HER2/neu. The preliminary results are very promising, and these combinations will soon be tested in the adjuvant setting. Cisplatin, carboplatin, and perhaps, oxaliplatin appear to have some antitumor activity in MBC and can be combined safely with other agents that are active in this disease. However, the precise role that platinum compounds play in the treatment of breast cancer remains to be defined.

This study evaluated conservative joint-sparing surgery for patients with osteosarcoma around the knee. Of 23 patients with stage IIB osteosarcoma around the knee, 5 were treated with long-term (30-56 weeks) local intensive preoperative chemotherapy consisting of high-dose methotrexate, intra-arterial and intravenous cisplatinum, doxorubicin, and hyperthermic isolated regional perfusion. More conservative resection, sparing the knee joint, was performed with smaller sufficient surgical margin in these 5 patients, preserving good limb function. Excellent local effects were achieved in the resected specimens. These results suggest long-term local intensive preoperative chemotherapy, including intra-arterial cisplatin and hyperthermic isolated regional perfusion, help control local tumor and allow for more conservative surgery.

Recently, the Dutch Society for Medical Oncology published new consensus guidelines for the use of adjuvant systemic treatment in patients with operable breast cancer. We used data of the cancer registry of the Comprehensive Cancer Centre South to predict the change in the number of patients who will be candidates for systemic treatment according to these new guidelines. It was estimated that of all patients with operable breast cancer, 15% should receive chemotherapy, 27% hormonal therapy and 17% a combination of both modalities. Of the patients with negative axillary lymph nodes, one-third will receive adjuvant systemic treatment. Compared with the previous guidelines, the introduction of the new guidelines will cause a 50% increase in the number of patients receiving adjuvant systemic treatment in Dutch hospitals.

Objective: To assess the effect of oestrogen (ER) and progesterone (PgR) receptors on the prognosis of patients with operable breast cancer and the decision to treat these patients with adjuvant tamoxifen., Design: Retrospective., Setting: Eight community hospitals in the Southeast Netherlands., Method: Using the registry of the Comprehensive Cancer Centre South, 2862 breast cancer patients were identified with stage I, II or IIIA tumours, treated during the period 1984-1992., Results: ER and PgR status were known for 2393 (84%) and 1761 (62%) patients respectively. From 1991, over 80% of the postmenopausal, lymph node positive patients had received tamoxifen, irrespective of the steroid receptor status. Of all lymph node negative patients fewer than 3% received adjuvant systemic treatment. Among the lymph node negative patients the steroid receptor status was not a significant predictor of survival. Among the lymph node positive patients whose tumours were both ER-negative and PgR-negative, a 2.8-fold increased risk of death was found during the first four years after primary treatment. The risk of death was not increased if only the ER or only the PgR status was negative., Conclusion: This study shows that ER and PgR receptors are significant prognostic factors for survival in breast cancer patients with involved axillary lymph nodes. The prognostic effect appeared to be restricted to the first four years after primary treatment. Selection of patients for endocrine treatment should be based on the steroid receptor status, considering the importance of the steroid receptors for predicting the response to endocrine treatment.

Medulloblastoma is the most frequent malignant brain tumor in pediatric patients. Early treatment strategies, combining surgery and radiotherapy alone, resulted in survival rates of about 40% only. In the last 15 years, chemotherapy was used more frequently in combination with surgery and radiotherapy. The rationale was to increase the survival rate and to decrease radiation toxicity in young children. Forty-six patients younger than 16 years were treated between July 1977 and September 1995 in our institution (32 boys and 14 girls). Thirty-nine patients could be evaluated according to their postoperative treatment with regard to different protocols such as SIOP 1, SIOP 2, HDMTX/VCR, HIT protocol 89/91 and Carbo-PEI (one patient). In total, 21/39 patients are alive without evidence of disease (EFS 55 +/- 7%) with a follow-up of 26 to 210 months. Four children are lost to follow-up. Twelve patients died after relapse, 1 child died of MTX-induced brain atrophy, 1 patient developed a secondary malignancy (acute lymphoblastic leukemia) and died. The best results were seen in patients treated according to the HIT 89/91 protocol as first-line treatment (CR 9/10). The improvement in outcome of our patients with medulloblastoma in recent years suggests the benefit of intensified chemotherapy on survival. In addition, refinement in surgical and radiological treatment have certainly also contributed to the better results.

Medulloblastoma, a malignant tumor arising from the medullary velum, is the most common malignant brain tumor of childhood. Local extension into the cerebellar hemisphere, infiltration of the floor of the fourth ventricle, and seeding into the subarachnoid space are common. Early diagnosis and improved treatment consisting of surgery followed by radiation and chemotherapy for selected high-risk patients has contributed to a dramatic change in survival. This article reviews current treatment strategies and describes new therapies that have the potential to improve the outlook of children with medulloblastoma.

Adjuvant chemotherapy improves the disease-free and overall survival of patients with resectable, early-stage breast cancer. However, the effect is modest, and we need means of increasing its impact. Retrospective and prospective studies on the effects of increased drug dosage have demonstrated that within some dose ranges, increasing the dose intensity (total drug dose divided by total treatment time) improves the outcome of treatment. Dose escalation to higher levels, sufficient to require growth factor and autologous stem cell support, is the subject of ongoing randomized study. Because there are both theoretical and practical limits on the potential effectiveness of single-cycle, high-dose chemotherapy, researchers are developing alternative means of increasing the effect of chemotherapy. One theoretically advantageous approach, predicted to be superior by kinetic models, is "dose-dense" chemotherapy administration. This approach consists of multiple cycles of escalated-dose chemotherapy administered at very short intervals. When administering presumed non-cross-resistant regimens or agents with overlapping toxicity, clinicians can increase dose density by using the sequential treatment plan. Furthermore, this plan can also facilitate the addition of new active drugs.

The consequences of lawsuits brought by patients to obtain insurance coverage for autologous bone marrow treatment for breast cancer illustrate the problems that arise when health plans seek to exclude "experimental" treatments.

Large-scale studies now provide relatively clear guidelines for the clinician on antiestrogen treatment in various patient populations and subgroups. Future challenges are to determine whether antiestrogens might be used for prevention, to identify the environmental and genetic causes of breast cancer, and to develop new approaches to this tumor, such as antiprogestins.

In the past decade, neoadjuvant and concomitant multimodality therapies have been studied in patients with cervical cancer. The past year has witnessed more pilot studies confirming the feasibility of multimodality therapy. It is now time to move to prospective randomized clinical trials to determine the effects on disease-free intervals, to examine survival rates, and to define the ideal chemotherapeutic regimen and relationship to radiation therapy or surgery.

Thirty-three patients treated primarily with surgical excision of pulmonary metastases from breast cancer were compared with 30 patients treated primarily with systemic chemohormonal therapy. Treatment for patients in the surgical group included pulmonary resection alone in 20, resection plus adjuvant systemic therapy in nine, and resection plus adjuvant radiation therapy in four. Treatment for patients in the medical group included systemic therapy alone in 22 and systemic therapy plus local radiation therapy in eight. Mean survival in the surgical group was significantly longer than that in the medical group, even when only those patients who manifested single pulmonary nodules were compared (58 months vs 34 months). The overall 5-year survival rate after treatment of lung metastasis was significantly greater for the surgical group than for the medical group (36% vs 11%). The results of this study indicate that surgical resection should be considered in patients with breast cancer who develop operable pulmonary metastases without evidence for concomitant extrapulmonary disease. In selected patients, such therapy may result in a survival benefit.

To determine the significance of small (< or = 5 cm in diameter) soft-tissue sarcoma of the extremity, 174 adult patients were identified from information that had been entered prospectively into a database of 1742 patients between July 1982 and December 1990. Median follow-up was 48 months. The majority of tumors were high grade (n = 114; 66%). Local recurrence (n = 17) was seen in patients with both high-grade (11%) and low-grade tumors (7%). Distant metastases were seen in 7% of high-grade tumors and in no low-grade tumors. The overall 5-year survival rate was 94% for all patients. Grade, depth, location, type of operation, and sex did not affect 5-year survival or local recurrence-free survival. Neither postoperative adjuvant chemotherapy nor radiation therapy resulted in superior 5-year survival or local recurrence-free survival when compared with no postoperative treatment. The prognosis of these lesions is favorable, and no additional prognostic factors were identified. Inclusion of these patients into adjuvant therapy trials examining survival is inappropriate.

Chemoradiation prior to pancreaticoduodenectomy ensures that all patients who undergo resection complete multimodality therapy, avoids resection in patients with rapidly progressive disease, and allows radiation therapy to be delivered to well-oxygenated cells before surgical devascularization. Twenty-eight patients with cytologic or histologic proof of localized adenocarcinoma of the pancreatic head received preoperative chemoradiation (fluorouracil, 300 mg/m2 per day, and 50.4 Gy) with the intent of proceeding to resection; all 28 completed this preoperative therapy. Hospital admission because of gastrointestinal toxic effects was required in nine patients, yet no patient experienced a delay in operation. Restaging was performed 4 to 5 weeks after completion of chemoradiation, and five patients were found to have metastatic disease; the 23 patients without evidence of progressive disease underwent laparotomy. At laparotomy, three patients were found to have unsuspected metastatic disease, three patients had unresectable locally advanced disease, and 17 patients were able to undergo pancreaticoduodenectomy. One perioperative death resulted from myocardial infarction, and perioperative complications occurred in three patients. Histologic evidence of tumor cell injury was present in all resected specimens. Our results suggest that pancreaticoduodenectomy can be performed with a low incidence of complications after chemoradiation for localized adenocarcinoma of the pancreas.

The charts of 44 women who underwent 47 immediate postmastectomy prosthetic breast reconstructions (IPMPBR) with subpectoral prostheses (long-term implant, long-term expandable implant or tissue expanders followed by long-term prosthetic placement) were retrospectively reviewed. Follow-up was from 3 to 49 months (median 18 months). Patient ages ranged from 31 to 77 years (median 42) but 82 per cent were under 60 years old. Indications for mastectomy were infiltrating cancer in 30 patients, intraductal cancer in 11, lobular carcinoma in situ in two and prophylaxis in one. There were 11 patients with pathologic Stage I, 15 with Stage II, three with Stage III and one with Stage IV breast cancer. Adjuvant chemotherapy (CTX) was given to 17 women, adjuvant hormonal treatment to nine, and radiation therapy (RT) to five. One patient had prosthesis extrusion and removal. Two patients had late periprosthetic infections (PPI) with consequent prosthesis removal. CTX did not have a significant association with PPI (two of 14 with CTX vs 0 of 29 without, P = 0.1). However, fill port migrations, prosthesis deflations, and greater than 1 complication were significantly associated with these infections (two of three vs 0 of 38, P = 0.004; two of two vs 0 of 45, P = 0.001; two of four vs 0 of 43, P = 0.006). Skin flap cellulitis and postoperative seroma were also associated with PPI (P less than 0.003 and less than 0.006, respectively). These factors were all also significantly associated with involuntary prosthesis loss (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Ten patients, seven women and three men, ages 47 to 76 years (mean 58.6 years), treated for adrenal cortical carcinoma between 1971 and 1989, were reviewed. Three (30%) of the tumors were nonfunctioning. The remaining seven (70%) were functioning, six of them occurring in women. Common presenting features were hormonal excess, distant metastases, weight loss, and abdominal pain. The primary tumor was resected in all patients, only two of whom had disease confined to the adrenal gland. Tumor diameter ranged from 9 to 21 cm (mean 15.7 cm). Inferior vena caval or right atrial extension of tumor thrombus was present in two patients. Excluding two deaths from postoperative complications, seven patients died of their disease after a mean survival of 25 months (range 2 to 84 months). Of seven patients who received o,p'-DDD treatment for metastatic or recurrent tumor, three (43%) had an objective response. In two patients, tumor regression was complete and was associated with prolonged survival. The first patient underwent resection of recurrent tumor on two occasions in addition to receiving o,p'-DDD and survived 84 months. The second patient had complete regression of pulmonary and liver metastases confirmed at laparotomy and thoracotomy and remains free of disease at 78 months. None of the five patients treated with various combinations of cytotoxic chemotherapy had an observable response, and no measurable effect was seen in a single patient following abdominal radiotherapy. It is concluded that resection for local recurrence may prolong survival and that significant and lasting tumor regression is possible with o,p'-DDD administration. Beneficial results from cytotoxic agents, however, could not be demonstrated.

The value of adjuvant systemic therapy has been clearly demonstrated in both node-positive and node-negative patients. However, there are many women with favorable prognoses whose breast cancer recurs. It has been possible only recently to identify subsets of patients who are at definite risk for recurrence. Advances both in selection and treatment of patients with early-stage breast cancer are being made as critical research questions are delineated and examined in prospective randomized trials.