Human cancer natural history, radiation induced immunodepression and post-operative radiation therapy

For several types of cancers, post-operative radiation therapy is able to reduce the incidence of local recurrences, but has only a relatively small beneficial effect on total survival. Conversely to what has been claimed, this discrepancy is not due to a detrimental effect of radiotherapy. The data do not substantiate the hypothesis that irradiation through an impact on the immune system enhances growth of neoplastic foci outside of the irradiated volume. Several sets of data show that uncontrolled primary tumors or lymph node metastases can be important foci for distant spread. However the analysis of the data shows that post-operative radiotherapy can prevent metastatic spread only in a small subset of patients, those without distant metastases at the initial treatment and in whom local recurrences can be a nidus for distant dissemination before being detected and treated. The results of the clinical trials carried out on patients with breast cancers show that this situation is frequently observed in patients with tumors located in the inner quadrants of the breast who are those in whom the involvement of the internal mammary chain is relatively frequent.     

Local and distant recurrence after conservative management of “very low-risk” breast cancer are dependent events: a 10-year follow-up

Purpose: To determine the risk factors associated with recurrence after breast-conserving treatments, and the relationship between occurrence of a local recurrence and subsequent distant metastases.Methods and Materials: Among the 3697 patients with primary breast cancer treated at Institut Paoli-Calmettes Cancer Center, Marseille, between 1980 and 1995, we retrospectively analyzed 756 patients who had been treated with conservative surgery with uninvolved margins of excision, were node-negative, and had received uniform radiotherapy and no chemotherapy. One third of the patients received hormonal therapy via tamoxifen or surgical castration. The endpoints considered were local failures and distant metastases. All tumors were reviewed by our pathologists. The median follow-up for the 700 survivors was 62 months.Results: In the multivariate analysis, histological multifocality (p = 0.0076), peritumoral vessel invasion (p = 0.0215), and young age (p = 0.0245) were associated with an increased risk of local recurrences, whereas tumor size (p = 0.0013), young age (p = 0.003), and histological multifocality (p = 0.0414) were associated with an increased risk of distant metastases. Local recurrences and distant metastases had similar yearly-event probabilities. Median time to distant metastases was shorter after a local recurrence. Early timing of local recurrences did not mark a higher risk of distant metastases. Hazard of relapsing from distant metastases was 4.4 times higher after a local recurrence.Conclusion: our results support the hypothesis that, in this subset of patients, local recurrences favor further dissemination of cancer cells. We are unable to clearly identify a group who would benefit from more aggressive local therapy.     

Survival and Pattern of Failure Following Locoregional Recurrence of Breast Cancer

This study analyzed prognostic factors at primary diagnosis and at first recurrence for impact on survival after isolated locoregional failure. The aims were: (1) assessment of prognostic factors for time to second locoregional failure, distant failure, and survival in isolated locoregional recurrence of breast cancer after mastectomy; and (2) investigation of the impact of a second locoregional failure on dissemination and survival.Between 1983 and 1985, 99 patients who had undergone mastectomy and then developed isolated local and/or regional recurrences, were treated with radical excision and radiotherapy; none of these patients had distant metastases. Survival and the times to second local failure and distant metastasis were analyzed according to potential prognostic factors.The median follow-up was 123 months; 38 patients were still alive. Median survival was 89 months and the 10-year survival rate was 38%, with no difference between local and regional recurrences. A total of 43 patients developed a second locoregional recurrence after a median of 73 months; primary tumour size and initial node status were significant independent prognostic factors. The annual hazard rates for recurrence were similar for patients developing local failure or systemic recurrence. The 10-year rate of dissemination was 49% for patients with locoregional control, compared with 51% for patients who had a second locoregional recurrence. The prognostic factors for survival were node status at mastectomy and haemoglobin level at first recurrence.The development of a second locoregional recurrence was not associated with an increased risk of dissemination or reduced survival. Differences in prognostic factors for locoregional control and distant metastases suggest that these recurrences represent different biological entities that require different treatment strategies. However, as the achievement of locoregional control had no influence on prognosis, the use of systemic adjuvant therapy may be warranted in a subset of these patients.     

Natural history of human cancer and prognostic factors. The example of breast cancer

The most important event during the growth of a human cancer is the occurrence of distant spread. A model of the natural history of breast cancer was developed which was used for several aims. It has been possible to study the relationship between the size of the breast tumor and the probability of dissemination either in regional lymph nodes or in distant sites. It was found that the distribution of tumor volume at metastatic dissemination is log normal with a median (termed V50) of 23.6 ml (diameter 3.5 cm). The number of involved axillary lymph nodes and the histological grade have both an impact on the dissemination probability and the size of the V50. It is also possible to estimate the median volume of the primary at the involvement of the first axillary node, of the second, of the third... On average, the V50 for distant metastatic dissemination is greater than the volume of the tumor at the initiation of the second axillary node but smaller than the volume at the initiation of the third. Another study was the assessment of the time at which the metastases were initiated. The results concerning age of metastases at the time of initial treatment allow to estimate the reduction in the incidence of distant metastases which can be obtained by an earlier diagnosis; these estimations are consistent with data of screening programs. The size of the occult metastases at the time of treatment of primary tumor was calculated. It was found that this size is much larger in the subset of patients with pejorative prognostic factors which probably explains the relatively low effectiveness of adjuvant chemotherapy in these patients. The maximum size of the metastases which are controlled by adjuvant chemotherapy was found equal to 1.5.10(6) cells. Finally the model was used to investigate the possible dissemination arising from loco-regional recurrence. The discrepancy between the great reduction in the incidence of loco-regional recurrences obtained with post-operative radiotherapy and its relatively small impact on survival is probably due to the fact that a recurrence has an impact on survival only in patients without distant metastases at the time of initial treatment and in whom the recurrence was not detected and treated before it reached the size at which it can initiate a metastasis. This situation is likely to occur only in patients with tumors of the inner quadrants in whom the internal mammary chain has a great likelihood of being involved.     

Influence of local recurrence on survival in patients with extremity osteosarcoma treated with neoadjuvant chemotherapy: the experience of a single institution with 44 patients

BACKGROUND: Risk factors for local recurrence (LR) after osteosarcoma, such as surgical margins and histologic response to preoperative treatment, have been well documented, whereas the outcome for patients who locally recur has not been well established yet. METHODS: Retrospective analysis of the management and outcome of 44 patients who developed LR after treatment of osteosarcoma of the extremities with neoadjuvant chemotherapy was performed in a single institution between 1983 and 1999. RESULTS: In 24 patients (54.5%), LR was the first sign of recurrence; in 8 patients (18.2%) LR followed systemic recurrence and in 12 patients (27.3%), the 2 events, local and systemic recurrence, were concurrent. Of the 44 patients, 26 with local recurrences were free of disease, but only 5 were long-term event-free survivors, and 39 patients developed further recurrences: 37 died of the tumor and 2 were alive with uncontrolled disease at the time of last follow-up. The 5-year disease-free survival rate after the last recurrence was 15.9%; it was 25.9% for patients who achieved remission and 0% for the others. The only prognostic factor identified for post-LR disease-free survival was the presence of systemic recurrence at the time of diagnosis of LR or before (5-year postrecurrence event-free survival rate of 29.1% for patients without metastases at the time of local recurrence vs. 0% for those with metastases; P = .02). CONCLUSIONS: These results confirm that patients with osteosarcoma of the extremities who develop LR are at a very significantly high risk of developing metastatic disease and dying of the tumor.     

Soft tissue sarcoma: The enigma of local recurrence

Local recurrence following the treatment of soft tissue sarcoma has been long recognized as a grave prognostic sign. Nevertheless, many investigators have recently suggested that local recurrence following limited surgery (“local persistence”) may be a manifestation of a tumor's size and metastatic potential and not a cause of tumor cell dissemination. The author reviewed the experience of several investigators with local persistence. This event was not found to be a threat to survival. The author offers an explanation for this unexpected finding. Soft tissue tumors vary widely in their metastatic potential, and patients also may vary widely in their ability to resist the distant implantation of circulating tumor cells. Patients with a low level of host resistance may be more susceptible to both distant metastases and local persistence, and vice versa. Weaker patients succumb to their initial tumor. Patients who survive the circulating tumor cells from their primary tumor may be immunologically prepared to survive the local persistence of a similar volume of tumor without developing distant disease. © 1993 Wiley-Liss, Inc.     

Locoregional recurrences after 649 modified radical mastectomies: incidence and significance

A continuous series of 649 patients, treated by modified radical mastectomy for primary breast carcinoma, is analyzed after a median follow-up of 92 months. 'True isolated' locoregional recurrences (LR), defined as LR not preceded or followed by distant metastases within 6 weeks, appeared with a cumulative actuarial incidence rate of 6%, 14% and 19% after 1, 5 and 7 years respectively, whereas the respective figures for distant metastases (M1) were 10%, 37% and 48%. The main initial parameters, predicting both the LR-free and the M1-free interval, are presented by statistical analyses in the following order of importance: number of invaded lymph nodes in the axilla, tumor size (T) and histological grading of differentiation. The same factors also predicted the imminence of M1 once LR had occurred, as well as survival after LR. A higher incidence of M1 after LR was also correlated with estrogen-receptor negative tumors and with those LR occurring within one year after mastectomy. LR occurred at the chest wall (65%), in the sub-clavicular fossa (16%) and the axilla (6%); the remaining 13% occurred in two of the sites. There was a trend towards longer survival after chest wall recurrence than after LR recurrence at another site. Axillothoracic irradiations postmastectomy gave a lower rate of LR in 227 patients than did a regimen of 12 months adjuvant chemotherapy with irradiation restricted to the internal mammary lymph nodes in 120 subsequent patients: 17 vs 25% at 5 years (P = 0.03 when adjusted by initial nodal involvement and T-size). Total excision of LR (repeated if new LR occurred) gave better rates of local ultimate control and survival than other kinds of treatments, with or without adjuvant local or systemic therapy. LR is not always a sign of imminent generalized disease. Actuarial 5-year survival after LR is 26.2% overall whereas, if only 'true isolated' LR are considered, the survival is 37%.     

Pattern of dissemination and survival following isolated locoregional recurrence of breast cancer

Purposes: The study evaluates prognostic factors for dissemination and survival in patients with local or regional recurrence of breast cancer. Furthermore, the aim was to define subgroups of patients at different risk of developing metastases in specific anatomical sites. Patients and methods: The study included 140 patients with isolated local or regional node recurrence, who entered a prospective study for staging of patients with first recurrence of breast cancer in the period 1983–85. The primary treatment was a simple mastectomy; node positive patients received adjuvant radiotherapy and chemotherapy or tamoxifen.If possible, the locoregional recurrence was treated with surgery and/or radiotherapy, otherwise by systemic therapy. Results: Median follow up was 10.4 years; 78 patients developed distant metastases (soft tissue, 32%; bone, 45%; viscera 40%). Median time to dissemination was 4.4 years, and the ten year dissemination rate was 72%. Median time to dissemination was 3.7 years for patients with recurrence in the regional nodes compared to 6.5 years for patients with chest wall recurrence only, p = 0.05. No specific time sequence (temporal pattern) was observed in the anatomical distribution of metastases, and the anatomical site of recurrence could not be predicted by any of the prognostic factors. At follow up, 93 patients had died. The median survival was 5.6 years and 30% were alive after 10 years. Forty-three of the 99 patients who received local therapy only did not develop metastases. Fifteen of these patients died without evidence of metastatic disease while 28 patients were still alive without distant recurrence after a median follow up time of 9.3 years (range, 6.5–11.9 years). Level of LDH and the number of positive regional nodes (NPOS) at primary diagnosis were significant independent prognostic factors for survival after recurrence. Conclusions: Approximately one third of the patients receiving local treatment only, were alive and without distant metastases up to ten years after locoregional recurrence, indicating that there is a subset of patients which may be long term survivors after local treatment only (surgery or radiotherapy). The duration of survival can be estimated by LDH and NPOS, but the model needs validation in a separate data set before clinical use.     

Prognostic factors for death after an isolated local recurrence in patients with early-stage breast carcinoma

BACKGROUND: The authors analyzed the outcome of patients with early-stage breast carcinoma after an isolated local recurrence, taking into account initial tumor characteristics and the type of initial treatment and local salvage treatment. METHODS: One hundred five patients were studied who presented with a breast tumor measuring 相似文献   

Papillary microcarcinoma of the thyroid-Prognostic significance of lymph node metastasis and multifocality

BACKGROUND: It is known that patients with papillary microcarcinoma (PMC) of the thyroid gland have a very favorable prognosis. The rising incidence of PMC among papillary thyroid carcinoma (PTC) necessitates the identification of prognostic factors and the formulation of treatment protocols. METHODS: The authors conducted a retrospective analysis of 203 patients with PMC who were diagnosed on or before 1999 and were treated at the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. RESULTS: The cause specific survival, locoregional (LR) failure free survival, and distant metastases failure free survival rates at 10 years were 100%, 92.1%, and 97.1%, respectively. Five patients had lung metastases; 2 patients died of their metastases 12.9 years and 14.8 years after diagnosis, and 3 patients achieved clinical remission after radioiodine (RAI) treatment. Twelve patients had LR recurrences. Patients with LR recurrence were highly salvageable with a combination of surgery, RAI treatment, and external radiotherapy; all but one (who refused treatment) were alive without disease at last follow-up. Multivariate analyses did not reveal any independent prognostic factor for survival. The risk of cervical lymph node (LN) recurrence increased 6.2-fold (P = 0.01) and 5.6-fold (P = 0.02) when LN metastases and multifocal disease were present at diagnosis. RAI ablation reduced the LN recurrence rate to 0.27 (P = 0.04). The presence of LN metastasis increased the rate of distant metastasis 11.2-fold (P = 0.03). Age was not a significant factor in predicting disease recurrence or survival. Subdivision by tumor sizes 5 mm did not affect the outcome, but no patient with tumors 相似文献   

Radiotherapy and hyperthermia with curative intent in recurrent high risk soft tissue sarcomas

Purpose: Radiotherapy before or after resection is one of the pillars of treatment for localised high risk soft tissue sarcomas. Treatment intensification has been described with concurrent chemotherapy and hyperthermia. The aim of this study is to assess local control after multimodal treatment, focussing on the treatment of local recurrences after surgery only.

Patients and methods: Of 42 patients treated in a prospective protocol with radiotherapy and hyperthermia, nine were treated for isolated local recurrences without metastatic spread. Most patients were treated with trimodal therapy including chemotherapy with ifosfamide and underwent resection whenever possible. Median follow-up was 1.4?years.

Results: The treatment was well tolerated. Estimated disease free survival, distant metastases free survival and local control for the whole cohort after 1.5?years were 66, 73 and 88%, respectively. Neoadjuvant vs. adjuvant treatment influenced local control with a trend to statistical significance. Resection status did not influence local control. The cohort of patients treated for local recurrence after surgery alone had a significantly impaired local control compared to multimodal treatment at primary diagnosis (100 vs. 52%, p?Conclusions: With multimodal therapy including radiotherapy and hyperthermia local tumour control is achievable even in locally recurrent tumours. The clear-cut difference of the treatment of local recurrence in contrast to primary diagnosis might either reflect difficulties in diagnosis and treatment of local recurrences or biological aggressiveness of recurrent tumours. However, we recommend to consider multimodal treatment at primary diagnosis of high risk soft tissue sarcomas.     

Adenoid cystic salivary gland carcinoma. A histopathologic review of treatment failure patterns

Seventy-one cases of adenoid cystic salivary gland carcinoma were reviewed according to treatment modality and clinical course. Thirty-six patients (51%) were treated by combined surgery and radiation therapy. The tumors were classified by their histologic patterns into tubular, cribriform, and solid forms. Distant metastases, in 52%, were the most frequent and ominous sources of failure. In 35% of cases, distant metastases developed despite local control at the primary site. In this group, the disease had a more fulminant course with shorter survival. Histopathologically, the cribriform subtype was associated with multiple local recurrences, greater local aggressiveness, and a poorer salvage rate as compared with the tubular subtype. Late onset of local recurrences and distant metastases was especially associated with the cribriform subtype. Overall prognosis in terms of distant metastases and survival was worst for the solid subtype. Control of local disease is best achieved with combined surgery and radiation therapy. The high incidence of distant metastases may not be affected by this regimen. The ultimate outcome of therapy is poorly predicted. Survival appears to be based on the pattern in which distant metastases develop. Overly aggressive and mutilating surgical approaches for these tumors are not recommended in many instances. The need for the development of new, more effective forms of therapy is emphasized.     

Hyperthermia and radiation therapy in the treatment of recurrent Merkel cell tumors

A high incidence of local recurrence, spread to regional lymph nodes, and distant metastases has been reported after surgical excision of Merkel cell tumors (MCT). The use of postoperative radiation therapy and/or chemotherapy is reviewed from the literature. Despite adjuvant treatment, local tumor recurrences frequently develop. Two patients are presented with metastatic MCT recurrent in previously irradiated sites who had excellent clinical responses and local control following retreatment with local hyperthermia in conjunction with low to moderate dose radiation therapy. These patients represent the first reported use of hyperthermia in the management of MCT. The encouraging local responses described suggest a potential role for the use of hyperthermia and concomitant radiation therapy in the treatment of recurrent MCT.     

Evaluation of modalities for recurrent breast cancer patients

Of 342 breast cancer patients radically operated on in the Second Department of Surgery, School of Medicine, Chiba University during 1965-1988, treatment for 75 recurrent patients were evaluated by the initial modes of recurrence. The modes of recurrence were classified into distant metastases, local lymph node recurrence (axillary, parasternal and supraclavicular nodes) and chest wall recurrence according to the General Rules for Clinical and Pathological Recording of Breast Cancer. Of 75 recurrent patients, distant metastases were seen as common as 77.3%, followed by recurrences of local lymph nodes (14.7%) and chest wall (8.0%). The number of patients in each mode of recurrence increased in relation to increase in the size of tumor and the number of metastatic lymph nodes at the time of the first operation. Histologically, scirrhous carcinoma was most common in chest wall recurrence. 2-year disease-free survival rates of distant metastases, local lymph node recurrence and chest wall recurrence were 44.6%, 24.2% and 16.7%, respectively. 5-year survival of bone metastasis with chemo-endocrine therapy was as significantly favorable as 60%, compared to chemo- or radiotherapy alone (p less than 0.01). However, 5-year survival of lung metastasis with or without endocrine therapy revealed no significant difference. Local lymph node recurrence with the combination of resection, radio- and/or chemotherapy produced a trend toward showing more favorable survival than that without resection.     

Development of a metastatic human colon cancer xenograft model in the nude mouse

The objective of our experimental protocols was to develop a metastatic model for a human colon carcinoma xenograft in congenitally athymic nude mice. This model would be useful in evaluating the efficacy of radiolabeled monoclonal antibodies for detection and treatment of regional and distant metastases. The LS-174T human colon carcinoma line was used to establish primary subcutaneous tumors in nude mice. Mice were killed at varying time intervals to establish the incidence of spontaneous metastases. Only lung micrometastases were observed during the 2-month observation period. To increase the metastatic rate, the site of primary implantation was varied and/or surgical manipulations were performed. Excision of small primary tumors resulted in a low incidence of local recurrence and no distant metastases. However, with excision of large primary tumors, a high local recurrence rate was noted and over 30% of mice had gross metastases. Mice bearing hind footpad tumors underwent excision when tumors were at least 1 cm in size. There were no local recurrences, but by 8 weeks over 40% had large pulmonary metastases. The LS-174T tumor was also established as a primary implant in the spleen from which 10 to 15% of the mice developed liver or lung metastases. The LS-174T tumor can metastasize in the nude mice and the latter two models may prove very useful in imaging and therapy studies.     

Long-term results of local recurrence after breast conservation treatment for invasive breast cancer

PURPOSE: The outcome for women with a local failure after breast conservation treatment is not well described in the literature. Because local recurrence is a potentially salvageable event, this study was performed to evaluate the outcome of patients with local recurrence after breast conservation surgery and definitive radiation treatment. METHODS AND MATERIALS: The study population consisted of 112 patients with ipsilateral breast tumor recurrence. There were 100 isolated local recurrences and 12 local-plus-regional recurrences. There were 93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local recurrences. Local recurrences were detected by physical examination alone in 42 patients, mammography alone in 47 patients, and both modalities in 23 patients. All patients were initially treated with breast conservation treatment with or without systemic therapy and subsequently treated at the time of local recurrence with salvage mastectomy with or without systemic therapy. The mean and median follow-up times after local recurrence were 49 and 44 months, respectively. RESULTS: For the entire group of 112 patients, the overall survival at 10 years after local recurrence was 69%, the cause-specific survival was 71%, and the freedom from distant metastases was 47%. For the 93 patients with an invasive local recurrence, the overall survival at 10 years was 64%, cause-specific survival was 67%, and freedom from distant metastases was 44%. For the 93 patients with an invasive local recurrence, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) also predicted for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On multivariable analysis, interval from diagnosis to local recurrence was an independent predictor of overall survival (p = 0.03). Method of detection of local recurrence (physical examination vs. mammography vs. both methods) was borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%, respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that predicted for freedom from distant metastases were identified. There were three second locoregional failures on the chest wall. Two of the 19 patients with a DCIS local recurrence have died of metastatic breast cancer. Death was probably not related to their local recurrence, but rather a result of persistent risk from an invasive primary cancer. CONCLUSIONS: This analysis provides long-term data after salvage treatment for patients who experience local recurrence after breast conservation treatment. The variables of method of detection and interval from diagnosis to local recurrence are identified as having prognostic significance for overall and cause-specific survival. In view of the potential for long-term survival, aggressive attempt at salvage treatment is warranted for the patient with local recurrence after breast conservation treatment. Second local recurrence after salvage mastectomy is an uncommon event. Although DCIS local recurrences may not in themselves cause an increase in the risk of mortality, the risk from the primary invasive cancer persists.     

Fusion imaging to evaluate the radiographic anatomical relationship between primary tumors and local recurrences in retroperitoneal soft tissue sarcoma

BackgroundLocal recurrence (LR) of retroperitoneal soft tissue sarcoma (RPS) is a common and life-threatening event. The evaluation of the exact anatomical patterns of local recurrence might help to improve local treatment in RPS.MethodsOf our local database we extracted ten patients with LR of RPS with axial MRI and/or CT datasets of the primary tumor (PT) and the LR. Using the Osirix DICOM viewer Version v.3.9.4 64-bit (Pixmeo, Geneva, Switzerland) we performed a three-step fusion algorithm consisting of: a) 3-point co-registration of the axial datasets depicting the PT and the LR using three abdominal landmarks b) re-orientation of the datasets and c) image fusion. We evaluated the feasibility of this technique with regard to categorizing the localization of LR as within or distant from the PT.ResultsFusion imaging was feasible in seven out of ten patients. In the other three patients anatomical shifting of organs after surgery led to a relevant mismatch of anatomical landmarks and impeded interpretation of the fused images. In five of seven patients with successful fusion imaging, local recurrences were located within the anatomical borders of the primary tumor, in two out of seven patients local recurrences were distant to the primary.ConclusionsFusion imaging of primary tumors and local recurrences is feasible in most patients with RPS. Most local recurrences occurred within the anatomical localization of the primary tumor. For further investigations validation of the technique in larger patient cohorts is required.     

Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: Further support about the concept of tumor dormancy

Purpose To gather information on metastatic growth from the time-distribution of first treatment failure in breast cancer patients undergoing mastectomy alone.Methods: The risk of recurrence at a given time after surgery was studied utilizing the cause-specific hazard function. Recurrence was categorized as first treatment failure at any site, local-regional recurrence, distant metastases, and contralateral tumor. The risk distribution was assessed relative to tumor size, axillary lymph node involvement, and menopausal status.Results: A total of 1173 patients treated between 1964 and 1980 with mastectomy alone and no adjuvant therapy were studied. The hazard function for first failure presented an early peak at about 18 months after surgery, a second peak at about 60 months and then a tapered plateau-like tail extending up to 15 years. A similar risk pattern was detectable for both local recurrence and distant metastases, while the curve of contralateral breast tumors showed a near flat plateau. The risk of early local-regional and distant recurrences was much lower for tumors less than 2 cm in diameter than for larger tumors; the risk of late recurrence was similar for small and large primaries. Node-positive patients showed peaks four to five times higher than node-negative patients. Subdividing node-positive patients into 1–3 and > 3 node-positive subsets did not substantially change the general picture of tumor recurrence. The hazard functions for premenopausal and postmenopausal patients were virtually superimposable.Conclusions: The multipeak hazard curve suggests that the process resulting in overt clinical metastases may have discrete features. Primary tumor size could affect in different ways early and late metastases, while axillary node status should be related to the risk level, not to the risk pattern, and menopausal status does not seem to significantly affect the hazard distribution. Moreover, contralateral breast tumors, occurring at constant risk throughout the time, should be considered as second primary cancers. These findings could be reasonably explained by a tumor dormancy hypothesis, which assumes that micrometastases may be in different biological steady states, most of which do not imply tumor growth. Tumor or microenvironment changes could induce metastatic growth after given mean transition times from surgery and originate a discrete pattern of the hazard function.     

Are there patients with stage I rectal carcinoma at risk for failure after abdominoperineal resection?

The clinical courses of 64 patients undergoing abdominoperineal resection for Stage I lower rectal carcinoma (tumors confined to the muscularis propria without lymph node involvement) were reviewed to identify subsets at risk for failure. Twelve of 12 patients with tumors limited to the submucosa remained disease free without evidence of recurrence. Of the 52 patients with muscularis propria involvement, there have been eight failures with three patients having local failure only, three patients with local failure and distant metastases, and two patients with distant metastases only. The 6-year actuarial disease-free survival, local control, and freedom from distant metastases rates for patients with tumors invasive of the muscularis propria were 80%, 84%, and 88%, respectively. Patients with tumors exhibiting vascular/lymph vessel involvement were at even higher risk for failure. Although adjuvant treatment is infrequently advised for these patients, the use of radiation therapy and chemotherapy should be reconsidered for patients with Stage I lower rectal carcinoma, specifically for patients with tumors invasive of the muscularis propria with vascular/lymph vessel involvement.