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Background: Some investigators have suggested a decreased prognostic value for conventional prognostic factors over time in patients with breast carcinoma. The objective of this study was to assess the effect of prognostic factors on the risk of death in patients with breast carcinoma over a long follow-up., Methods: The authors assessed clinicopathologic prognostic factors in patients with early-stage breast carcinoma over a follow-up > 25 years and analyzed the variation of their effect on death in consecutive 5-year follow-up intervals. The study included 2410 women who primarily underwent complete surgical resection. Time-dependent variables were analyzed by using different multivariate models., Results: Four factors were related strongly to the risk of death in the first 5 years: tumor size, histologic grade, the number of involved axillary lymph nodes, and age at diagnosis. After 10-15 years of follow-up, only age at diagnosis was related to the risk of death. The effect of powerful prognostic factors, except age at diagnosis, on the risk of death was time limited, and no effects or very small effects were detectable after 10 years of follow-up., Conclusions: Conventional and widely accepted prognostic factors may explain a significant portion of early deaths among patients with early-stage breast carcinoma, but they were of limited value to explain late mortality, that also may be influenced by late events, such as new primary malignancies and treatment complications. Cancer 2006. (c) 2006 American Cancer Society.

The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer.

A multivariate analysis of the prognostic factors was carried out on a series of 546 differentiated thyroid cancers followed for 8 to 40 years. For survival, the highest risk factor was associated with age; tumors diagnosed in patients younger than 45 years had higher relapse-free survival (RFS) and total survival (TS) rates and a slower growth rate. In children, although the RFS and TS at 15 years were high, they decreased later. The second independent prognostic factor was histology. There was no difference between papillary and follicular well-differentiated (FWD) tumors, but follicular moderately differentiated (FMD) had lower TS and RFS. Among FMD cancers, relapses occurred earlier and the interval between relapse and death was shorter. The third factor was sex. Tumors tended to disseminate more in male than in female patients. The survival rate after relapse was the same, however, suggesting that the growth rates are not different. The presence of palpable lymph nodes also had a significant independent impact on both TS and RFS. Patients treated after 1960 have a better outcome than patients treated earlier, although they did not differ in age distribution, histologic characteristics, sex ratio, or incidence of palpable lymph nodes. The distribution of time intervals between treatment and relapse was not compatible with an exponential failure time model but fit with a log-logistic model. Relapses can occur as late as 30 years or more after initial treatment. Elevated levels of circulating thyroglobulin have been observed in about 12% of the patients who had been in complete remission for longer than 20 years.

Surgery is the most effective treatment for thyroid cancer; however, in some subsets of patients, the role of radiotherapy (RT) is important. The main indication for external-beam RT is incomplete surgery. When neoplastic tissue is left behind at operation, RT must be considered, but only if an experienced surgeon feels that everything that can be done has been done. Generally, in those patients, the neoplastic tissue involves the larynx, trachea, esophagus, blood vessels or mediastinum. Of 539 patients with differentiated thyroid cancer treated at Villejuif, France, until 1976, 97 were treated by external radiotherapy after an incomplete surgical excision. Fifteen years after irradiation, the survival rate is 57% and is approximately 40% at 25 years. The relapse-free survival is lower (39% at 15 years). In patients irradiated with an adequate dose (greater than or equal to 50 Gy) to residual neoplastic tissue after incomplete surgery, the incidence of local recurrence is low (actuarial probability of local recurrence 11% at 15 years versus 23% for patients treated by surgery alone, although the irradiated patients had larger and more extensive tumors). This demonstrates the efficacy of external-beam radiotherapy. The effects of radiotherapy on a residual tumor can be monitored by a serum thyroglobulin assay. With regard to local control of tumors, the effectiveness of radioiodine administration is clearly lower. However, since radioiodine facilitates early detection of distant metastases, a combination of external RT and radioiodine is indicated and is well-tolerated. For inoperable patients, the results of RT are limited: although complete remissions are sometimes obtained, the incidence of local recurrence is high. External RT is effective in medullary carcinoma despite the slow shrinkage of the tumor after irradiation. Assay of the calcitonin level helps to monitor the effects of the treatment during follow-up and has demonstrated in some patients the efficacy of cervical RT. In undifferentiated cancers, the results of RT are poor. Combination of RT and chemotherapy are being explored despite the disappointing preliminary results of this combination.

The association of radiotherapy (RT) and chemotherapy (CT) constitutes one of the main avenues for research in therapeutic oncology. This association has two aims: (1) increase in control rate of primary tumor (this requires either the potentiation of one of the two modalities by the other or the additivity of their effect on tumor cells without a parallel increase in the toxic effects on critical normal tissues); (2) spatial cooperation (RT being used for the control of the primary tumor or of the sanctuaries, and CT for the control of the disseminated disease). In these two strategies, RT and CT should be given up to full doses in order to be effective. The main risk is an increase in the number and severity of the early and late side effects. To circumvent this problem, two possibilities are being explored: (1) use of drugs without serious toxic effects on those critical tissues which are included in the irradiated volume; and (2) avoidance of concomitant administration and introduction of a sufficiently long-time gap between the completion of one modality and initiation of the other. However, in such sequential treatment, a delay of CT until after the completion of RT, or an interruption of CT cycle during the course of RT, allows the occult metastases to increase in size; a similar delay in initiation of RT is also detrimental, as drugs are often not effective on bulky tumors. Moreover, under CT, the cells which are resistant to the cytotoxic drugs may disseminate and initiate chemoresistant metastases. Taking these disadvantages into account, a treatment protocol was proposed in 1980 in which CT and RT are given alternately, without undue delay. Chemotherapy is started with the usual scheduling of one cycle every month. Radiotherapy courses are interdigitated between CT cycles. Each course is initiated 1 week after interrupting CT and continued until 1 week before beginning the subsequent cycle of chemotherapy, and so on until completion of RT. Such split-course RT should have an effect on a tumor comparable to that of a conventional fractionation. This protocol has been used on 24 patients with non-Hodgkin's lymphoma (NHL) of diffuse histology, and 63 patients with small cell carcinoma of the lung. The 2-year relapse-free survivals are promising (in clinical stage II NHL of diffuse histology, 75%; and in small cell lung carcinomas, 33%).(ABSTRACT TRUNCATED AT 400 WORDS)

The European Organization for Research on Treatment of Cancer (EORTC) trial 20781, concerning osteosarcoma of the limbs is reported. After definitive treatment of the primary tumor with amputation or irradiation, adjuvant treatment was given, randomized into either 9 months of chemotherapy according to a modified Rosen schedule, or elective bilateral lung irradiation of 20 Gy, or 3 months of chemotherapy followed by lung irradiation. The 4-year disease-free survival and total survival were 24% and 43%, respectively, with no difference between the treatment arms. In the radiotherapy arms the lung metastases were more frequently suitable for surgical treatment. The survival of patients with either tibia localizations or higher age was somewhat better. Local recurrences occurred in 16% of patients, 50% of them with distant metastases. The trial was executed from 1978 to 1983; 205 patients were evaluable and eligible, and three toxic deaths occurred in the chemotherapy arms. Elective lung irradiation provided the same survival as the adjuvant chemotherapy given in that time.

An analysis of 1059 patients with clinical stage (CS) I and II Hodgkin's disease was undertaken to determine the prognostic significance of the number of involved sites. In this group of patients the number of involved lymph node areas was highly correlated with the probability of dissemination of occult disease. In the subgroup of patients with involvement of two lymph node sites (CS II2) approximately 50% demonstrated occult dissemination on the other side of the diaphragm as evidenced by subsequent relapse in the untreated subdiaphragmatic region. However, only 15% to 20% of this group had unsuspected disease in regions other than the spleen or the paraaortic lymph nodes. In CS I and II2 supradiaphragmatic patients, who underwent a staging laparotomy, splenic involvement was a powerful prognostic indicator. When the spleen was not involved, less than 10% of patients had disease elsewhere below the diaphragm, whereas, when the spleen was involved as many as 40% of patients had additional subdiaphragmatic sites involved. In the subgroup with three or more lymph node areas involved (CS II3), the proportion of patients with extension of disease on the other side of the diaphragm, as evidenced by later relapse was also about 50%. But in these patients, unlike the CS II2 patients, analysis of relapse patterns showed that occult disease had already disseminated to the pelvic nodes or to extra nodal sites. Furthermore, splenic involvement was of much less prognostic significance because CS II3 patients who did not demonstrate splenic involvement at staging laparotomy had similar relapse incidence and similar relapse patterns as those with positive spleens.