High Risk Of Distant Metastasis Research Articles

Ipsilateral breast tumor recurrence (IBTR) after breast‐conserving treatment for early breast cancer

The clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long-term follow-up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group. Patients (N = 1901)with unilateral breast cancer < or = 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan-Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR. At a median follow-up time of 107 months, the 10-year overall and disease-free survival rates were 83.9% and 77.8%, respectively. The 10-year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10-year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676-5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis. Young age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases.

Post-hysterectomy radiotherapy in FIGO stage IB–IIB uterine cervical carcinoma

Objective This study is a retrospective analysis of stage IB–IIB cervical carcinoma patients who had received postoperative radiotherapy (PORT). Methods Eight hundred patients with stage IB–IIB cervical carcinomas who received PORT after radical hysterectomy and bilateral pelvic lymph node dissection (PLND) between February 1979 and March 2000 were analyzed. Results The median follow-up duration was 100 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 88% and 81%, respectively. One hundred forty-six patients (18%) failed, and 103 of these had distant metastases. Multivariate analysis revealed that pelvic lymph node (LN) metastasis significantly compromised OS, DFS, pelvic failure-free survival (PFFS), and distant failure-free survival (DFFS) ( P < 0.05). Patients with age <50 years, deep stromal invasion (DSI), and lymphovascular space invasion (LVSI) were significantly associated with a higher risk of distant metastasis after PORT. The incidences of late rectal, urinary, and small bowel complications of grade 3 or higher were 1.6%, 1.4%, and 1.0%, respectively. Conclusions PORT achieved good OS and DFS in the patients with risk factors after radical hysterectomy for stage IB–IIB cervical carcinomas. Distant metastasis was the major pattern of treatment failure after PORT. Effective systemic chemotherapy might be a breakthrough in improving the outcome of PORT in patients with cervical carcinomas.

High Expression of PRL-3 Promotes Cancer Cell Motility and Liver Metastasis in Human Colorectal Cancer

Overexpression of PRL-3 has been implicated in colorectal cancer metastases. We investigated the significance of PRL-3 expression in the progression and development of colorectal cancer. We transfected PRL-3-specific small interfering RNA into human colon cancer DLD-1 cells and analyzed its effect on proliferation, motility, and hepatic colonization. Using an in situ hybridization method, we examined the levels of PRL-3 expression in both primary (177 cases) and metastatic (92 cases) human colorectal cancers and elucidated the relationships with clinicopathological parameters including the incidence of metachronous liver and/or lung metastasis after curative surgery for primary tumor. Transient down-regulation of PRL-3 expression in DLD-1 cells abrogated motility (in vitro) and hepatic colonization (in vivo), but no effect on the proliferation of these cells was observed. In human primary colorectal cancers, the frequency of up-regulated PRL-3 expression in cases with liver (84.4%) or lung (88.9%) metastasis was statistically higher than that in cases without either type of metastasis (liver, 35.9%; lung, 42.3%). In metastatic colorectal cancer lesions, high expression of PRL-3 was frequently detected (liver, 91.3%; lung, 100%). Interestingly, metachronous metastasis was observed more frequently in the cases with high PRL-3 expression (P < 0.0001). These results indicate that PRL-3 expression in colorectal cancers may contribute to the establishment of liver metastasis, particularly at the step in which cancer cells leave the circulation to extravasate into the liver tissue. In addition, PRL-3 is expected to be a promising biomarker for identifying colorectal cancer patients at high risk for distant metastases.

Clinical use of positron emission tomography in the management of cutaneous melanoma

Cutaneous melanoma is the seventh most common newly diagnosed cancer among Americans. It frequently metastasizes and is difficult to treat. Accurate disease staging is important for optimizing therapy and selecting appropriate patients for experimental trials. Positron emission computed tomography (PET) using 18F-fluorodeoxyglucose (FDG) has been studied extensively since 1991 and shows great promise in the detection of metastatic cutaneous melanoma. Cumulative data from the last 13 years is reviewed in this article and suggest that FDG-PET is the modality of choice for evaluating patients who fit into one of four categories: 1) individuals with a high risk for distant metastases based on extent of locoregional disease, 2) patients with findings that are suspicious for distant metastases, 3) individuals with known distant tumor deposits who still stand to benefit from customized therapies if new lesions are discovered or treated lesions regress, and 4) patients at high risk for systemic relapse who are considering aggressive medical therapy. Despite the overall superiority of FDG-PET in the detection of melanoma metastases, limitations exist with respect to detection of small lung nodules and brain metastases, which are better evaluated by computed tomography and magnetic resonance imaging, respectively.

Comparison of whole-body MRI with automatic moving table technique and bone scintigraphy for screening for bone metastases in patients with breast cancer

The aim of this study was presentation of a whole-body MRI technique with a moving table as a screening tool for bone metastases in patients with breast cancer. Twenty-two patients with breast carcinoma underwent both a planar whole-body bone scintigraphy and whole-body MRI at 1.5 T. The MRI images were acquired with a moving table at six different anatomical positions within a measurement time of 20 min. Coronal images were acquired using a short-tau inversion recovery sequence, accomplished by an axial T2-weighted turbo-spin-echo sequence through the head, and a T1-weighted opposed-phase sagittal 2D fast low-angle shot sequence covering the whole spine. The MRI findings indicating bone metastases were compared with findings from bone scintigraphy. Metastatic lesions were confirmed by follow-up examinations over 1 year. Twelve patients showed bone metastases. Whole-body MRI was superior to bone scintigraphy in predicting lesion origin with a sensitivity of 92% (bone scintigraphy 83%), a specificity of 90% (scintigraphy 80%) and an accuracy of 91% (scintigraphy 82%). The MRI showed additional findings such as metastases of the lung and liver. Whole-body MRI with moving table technique may be an effective method of total body screening for bone in selected patients with breast carcinoma and a high risk of distant metastases, although with the higher costs of MRI bone scintigraphy must still be considered as the first method for screening patients with breast cancer.

Multimodality Management of Urachal Carcinoma: The M. D. Anderson Cancer Center Experience

Enteric type adenocarcinomas arising in the dome of the bladder or along the urachal ligament are uncommon. To improve our understanding of urachal carcinoma and define outcome with current management, we performed a retrospective review of cases seen at the M. D. Anderson Cancer Center. We reviewed the records of 42 patients with urachal carcinoma evaluated at our institution from 1985 to 2001. Specifically, we sought to evaluate the importance of extent of disease, surgical characteristics and systemic therapy on clinical outcome. Of the 42 patients 7 had clinically evident metastases at diagnosis and 35 had resectable disease that was managed initially with surgery. Overall survival from diagnosis for all 42 patients was 46 months with 40% surviving at 5 years. Of the resected cases 16 (46%) remain disease-free (median followup 31 months). Covariates associated with long-term survival were negative surgical margins (p = 0.004) and absence of nodal involvement (p = 0.01). Median survival from recognition of metastatic disease was 24 months in 26 patients in whom metastases ultimately developed. Chemotherapy for metastatic disease produced only 4 significant responses, including 3 of 9 patients treated with 5-fluorouracil and cisplatin containing regimens. Urachal carcinomas are usually locally advanced at presentation with a high risk of distant metastases. However, long-term survival following radical resection occurs in a significant fraction of patients (16 of 35 in our series), supporting an attempt at margin-negative, en bloc resection if at all possible. Chemotherapy appropriate for enteric type adenocarcinoma can induce objective responses but meaningful improvement in survival is not yet demonstrated.

Radiation to internal mammary nodes in medial tumors may compensate for higher risk of distant metastases and death in patients with early breast cancer

Purpose/Objective: Recent data suggest that breast cancer patients (pts) with medial tumors may have a 50% excess risk of both distant relapse and breast cancer death compared with lateral location. This has been shown for high-risk pts (Lohrisch et al., JCO 2000;18:2828-35) and unselected pts (Zucali et al., JCO 1998;16:1363-6). Since 1985 we have been prospectively following a consistent policy of radiation treatment (RT) of internal mammary (IM) and supraclavicular (SC) nodes in all pts with medial tumors. This analysis evaluates overall survival and distant metastases-free survival rates for an unselected group of pts with early breast cancer comparing long-term outcome between lateral and medial tumors.

438 Poster Radiation to internal mammary nodes in medial tumors may compensate for higher risk of distant metastases and death in patients with T1/2- breast cancer

438 Poster Radiation to internal mammary nodes in medial tumors may compensate for higher risk of distant metastases and death in patients with T1/2- breast cancer

Posttreatment prostate-specific antigen nadir highly predictive of distant failure and death from prostate cancer

Purpose: To link posttreatment biochemical profiles to distant failure and cause-specific survival by assessing the relationship between posttreatment prostate-specific antigen (PSA) nadir and PSA doubling time (PSADT) with these outcome measures.Methods and Materials: A total of 615 men were treated at the Fox Chase Cancer Center between April 1989 and December 1995 with three-dimensional conformal radiotherapy alone (median dose 73 Gy). The median follow-up was 64 months (range 2–135). Kaplan-Meier methods were used to estimate the rates of biochemical control, freedom from distant metastasis (FDM), and cause-specific survival. Multivariate predictors of outcome were assessed using stepwise Cox regression analysis.Results: Multivariate analyses demonstrated that the predictors of improved biochemical control were a lower PSA nadir (p <0.0001), lower pretreatment PSA level (p <0.0001), Gleason score of 2–6 (p = 0.001), Stage T1-T2a tumors (p = 0.03), and higher RT dose (p = 0.02). The predictors of improved FDM were a lower PSA nadir (p <0.0001), longer interval to nadir from start of treatment (p = 0.0002), Gleason score of 2–6 (p = 0.005), androgen deprivation for biochemical failure (p = 0.001), and Stage T1-T2a tumors (p = 0.01). The predictors of improved cause-specific survival were a lower PSA nadir (p = 0.006) and longer interval to nadir from the start of treatment (p = 0.03). The 8-year FDM rate was 96%, 89%, and 61% for PSA nadir values of ≤1.0, 1.1–2.0, and >2.0 ng/mL (p <0.0001), respectively. The 8-year cause-specific survival rate was 97%, 96%, and 78% for posttreatment PSA nadir values of ≤1.0, 1.1–2.0, and >2.0 ng/mL (p <0.0001), respectively. For patients with sufficient PSA follow-up for PSADT calculations (n = 136), multivariate analysis of FDM from the time of biochemical failure demonstrated that androgen deprivation (p = 0.001), longer PSADT (p = 0.003), lower PSA nadir (p = 0.02), and longer interval to nadir from start of treatment (p = 0.04) were independent predictors of improved FDM.Conclusion: This is the first study, to our knowledge, to demonstrate the overwhelming predictive power of posttreatment PSA nadir for distant failure and death from prostate cancer. It is also the first study, to our knowledge, to demonstrate a strong association between posttreatment PSADT and distant failure. The results provide new information regarding disease progression as a function of posttreatment PSA profiles (time to achieve nadir from start of treatment, nadir, and PSADT) and the timing of androgen deprivation for biochemical relapse. This study may be used for the early identification of patients at high risk of distant metastasis and who may be directed to applicable systemic treatment clinical trials.

Locoregional failure of postmastectomy patients with 1–3 positive axillary lymph nodes without adjuvant radiotherapy

Purpose: To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1–3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT).Methods and Materials: Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1–3 positive axillary nodes. The median number of nodes examined was 17 (range 7–33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months.Results: Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1–23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04), tumor size ≧3 cm (p = 0.002), negative estrogen receptor protein status (p = 0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size (p = 0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor ≧3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of 66.7% (95% CI 42.8–90.5%) compared with 7.8% (95% CI 2.2–13.3%) for the low-risk group (with 0–2 factors; p = 0.0001). For the 110 patients who received no adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9 of 17, 95% CI 24.6–73.4%). For patients without LRR, it was 13.3% (15 of 93, 95% CI 6.3–20.3%; p = 0.0001). The 4-year survival rate for patients with and without LRR was 75.1% (95% CI 53.8–96.4%) and 88.7% (95% CI 82.1–95.4%; p = 0.049), respectively. LRR was independently associated with a higher risk of distant metastasis and worse survival in multivariate analysis.Conclusion: LRR after mastectomy is not only a substantial clinical problem, but has a significant impact on the outcome of patients with T1 or T2 primary tumor and 1–3 positive axillary nodes. Patients with risk factors for LRR may need adjuvant RT. Randomized trials are warranted to determine the potential benefit of postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1–3 positive nodes.

A clinical study of 213 patients with laryngeal cancer

We retrospectively analyzed 213 patients--197 men and 14 women aged 40 to 87 years--with laryngeal cancer treated at our department from September 1986 to December 1997. The male to female ratio was about 12:1. Cases included 120 glottic (56.3%), 90 supraglottic (42.3%), and 3 subglottic (1.4%). Radiotherapy for early cases and surgery, mainly total laryngectomy for T3 and T4 were conducted first. The 5-year cause-specific survival by site was 97.6% glottic and 77.5% supraglottic. The five-year survival was 88.6% overall. Local control was 83.8% in glottic T1a and 84.6% in glottic T1b. The 3-year preservation of the larynx was 89.1% in glottic T1a and 92.3% in glottic T1b. Distant metastases were observed in 14 cases, mostly to the lung, bones, and liver. At high risk for distant metastasis were those with supraglottic T3-T4, N1, N2b, or pN2c.

Does histologic grade have a role in the management of head and neck cancers?

High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy. This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis. There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02). Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.

Preliminary results of the GORTEC 96-01 randomized trial, comparing very accelerated radiotherapy versus concomitant radio-chemotherapy for locally inoperable HNSCC

Purpose: In the past decades, results from randomized trials have shown that either modified fractionated radiotherapy (RT) or concomitant radio-chemotherapy (RT-CT) combinations were able to improve the therapeutic ratio of conventional RT in advanced head and neck squamous cell carcinoma (HNSCC). However few studies have directly compared these 2 modalities. In that aim, we initiated a randomized trial in a carefully selected population of HNSCC patients having both a locally inoperable tumor and a high risk of distant metastases (related to the importance of the nodal involvement).

High-risk groups of patients with Stage II colon carcinoma.

It is unclear whether patients with Stage II colon carcinoma should be offered adjuvant chemotherapy. Therefore, the authors analyzed the risk factors of these patients to identify high-risk subgroups who may benefit from such treatment. The data from 305 patients with Stage II colon carcinoma documented in the Erlangen Registry of Colorectal Carcinoma were analyzed to identify risk factors for distant metastasis and disease-related survival. The patients were divided into two subgroups: those in a low-risk group and those in a high-risk group. The data were then compared with those from 306 patients with Stage II colon carcinoma from the German Study Group for Colorectal Carcinoma (SGCRC). Emergency presentation, a primary tumor site in the left colon, pT3 tumors with a depth of invasion of > 15 mm beyond the outer border of the muscularis propria, and pT4 lesions were identified as the major risk factors for Stage II colon carcinoma. On dividing patients into subgroups according to these risk factors, it was found that patients in the high-risk group had a significantly higher risk of distant metastases and a significantly lower disease-related survival rate compared with patients in the low-risk group. On analyzing the SGCRC data, the authors also found a significantly higher rate of distant metastases in the high-risk group, but the disease-related survival rate differed only marginally. Among patients with Stage II colon carcinoma, it is possible to identify a high-risk group of patients who may be candidates for adjuvant chemotherapy. Stratification by the risk factors emergency presentation, tumor site, depth of tumor invasion, and surgical department should be employed in further clinical studies.

Down regulation of the tumor suppressor gene maspin in breast carcinoma is associated with a higher risk of distant metastasis

Background: Maspin (mammary serpin) is a relatively novel serine protease inhibitor with tumor suppressing function in breast cancer. Maspin expression was found in normal breast epithelial cells, but was decreased during tumor progression. Only a few systematic analyses of this phenomenon have been undertaken so far. In this study we developed specific nested reverse transcription polymerase chain reaction (RT-PCR) conditions for the detection of maspin expression in human breast carcinoma and assessed maspin’s association with the clinical behavior of primary breast cancers. Methods: Tumor specimens obtained from 45 primary breast cancer patients were analyzed for maspin expression by a nested RT-PCR assay. Recurrence free survival was evaluated and correlated to maspin expression. Results: The maspin transcript was detected in 29 (64%) breast cancer specimens whereas no expression was found in 16 (36%) cancer specimens. This expression was unrelated to any of the established prognostic factors. However, 6 out of 8 patients who developed distant metastasis (lymph nodes, lung, liver, bone, pleura) within 3 yr after their initial diagnosis showed no maspin expression of the primary breast cancer ( p < 0.05). Conclusions: The lack of maspin expression in breast cancer seems to be associated with a short disease free survival and supports maspin’s function as an indicator of tumor aggressiveness and metastatic potential. Nested RT-PCR is a sensitive method to determine maspin expression in human breast cancer tissue.

Lymph node metastasis in maxillary sinus carcinoma

Purpose: To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma. Methods and Materials: We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months. Results: The median survival for all patients was 22 months (range: 2.4–356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3–4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1–2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate ( p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse. Conclusion: The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3–4 SCC of the maxillary sinus.

Tumour prothymosin alpha content, a potential prognostic marker for primary breast cancer.

In a previous report we suggested that the estimation of prothymosin α (PTA) levels in primary breast tumours might be used to identify breast cancer patients at high risk for distant metastasis (Dominguez F et al (1993) Eur J Cancer29A: 893–897). Here the role of tumour PTA levels as predictor was investigated with respect to both disease-free survival (DFS) and survival. Tumours were obtained from a series of 210 consecutive female patients with ductal carcinoma who underwent surgery at the Hospital Xeral de Galicia (Santiago de Compostela, Spain). Characteristics including PTA tumour levels, number of positive axillary nodes, patient's age at surgery and tumour histological grade were significantly associated with DFS and survival, as determined by univariate analysis. Patients with tumours with low or moderate PTA levels demonstrated a statistically decreased rate of tumour recurrence and a statistically significant increased overall survival in comparison with those whose tumours had high PTA levels. Patient's relative risk of dying was 2.1 times greater for tumours with high PTA levels than for those tumours with low or moderate PTA levels. In conclusion, these data support the hypothesis that tumour high PTA levels is associated with a worse outcome. © 2000 Cancer Research Campaign

Postoperative irradiation of minor salivary gland malignancies of the head and neck

Objectives: (1) To review the Stanford experience with postoperative radiotherapy for minor salivary gland carcinomas of the head and neck. (2) To identify patterns of failure and prognostic factors for these tumors.Materials and methods: Fifty-four patients with localized tumors were treated with curative intent at Stanford University between 1966 and 1995. The 1992 AJCC staging for squamous cell carcinomas was used to retrospectively stage these patients. Thirteen percent had stage I, 22% stage II, 26% stage III, and 39% stage IV neoplasms. Thirty-two patients (59%) had adenoid cystic carcinoma, 15 (28%) had adenocarcinoma, and seven (13%) had mucoepidermoid carcinoma. Thirty (55%) had positive surgical margins and seven (13%) had cervical lymph node involvement at diagnosis. The median follow-up for alive patients was 7.8 years (range: 25 months–28.9 years).Results: The 5- and 10-year actuarial local control rates were 91 and 88%, respectively. Advanced T-stage (T3-4), involved surgical margins, adenocarcinoma histology, and sinonasal and oropharyngeal primaries were associated with poorer local control. The 5- and 10-year actuarial freedom from distant metastasis were 86 and 81%, respectively. Advanced T-stage (T3-4), lymph node involvement at diagnosis, adenoid cystic and high-grade mucoepidermoid histology were associated with a higher risk of distant metastases. The 10-year cause-specific survival (CSS) and overall survival (OS) were 81% and 63%, respectively. On multivariate analysis, prognostic factors affecting survival were T-stage (favoring T1-2), and N-stage (favoring NO). When T- and N-stage were combined to form the AJCC stage, the latter became the most significant factor for survival. The 10-year OS was 86% for stage I-II vs. 52% for stage III-IV tumors. Late treatment-related toxicity was low (3/54); most complications were mild and no cranial nerve damage was noted.Conclusions: Surgical resection and carefully planned post-operative radiation therapy for minor salivary gland tumors is well tolerated and effective with high local control rates. AJCC stage was the most significant predictor for survival and should be used for staging minor salivary gland carcinomas.

Reduction in New Metastases in Breast Cancer with Adjuvant Clodronate Treatment

Bisphosphonates are effective against the increased bone resorption caused by certain diseases because they inhibit the activity of osteoclasts. In patients who have breast cancer and metastatic bone disease, the bisphosphonate clodronate (clodronic acid) reduces the frequency of skeletal complications. Experiments in animals and preliminary clinical observations indicate that early clodronate therapy reduces the incidence of new bony metastases in breast cancer. We investigated the effects of clodronate on the incidence and extent of new metastases in patients with breast cancer. Between 1990 and 1995, 302 patients with primary breast cancer and tumor cells in the bone marrow (the presence of which is a risk factor for the development of distant metastases) were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for two years (157 patients) or standard follow-up (145 patients). The median length of observation was 36 months. All patients in both groups received standard surgical treatment and customary hormonal therapy or chemotherapy. Distant metastases were detected in 21 patients in the clodronate group and in 42 patients in the control group (P<0.001). The incidence of both osseous and visceral metastases was significantly lower in the clodronate group than in the control group (P=0.003 for both osseous and visceral metastases). Six patients in the clodronate group died, as did 22 in the control group (P=0.001). The mean number of bony metastases per patient in the clodronate group was roughly half that in the control group (3.1 vs. 6.3). Clodronate can reduce the incidence and number of new bony and visceral metastases in women with breast cancer who are at high risk for distant metastases.

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.