Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation

Purpose The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. Material and methods Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10–12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. Results The median age was 64.5 years (40–90). The median follow-up was 62 months (4–86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6–52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3–4 chronic toxicity was observed. Grade 1–2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. Conclusions IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment (AU)

Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.

PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.

Role of boost radiotherapy for local control of pure ductal carcinoma in situ after breast-conserving surgery: a multicenter, retrospective study of 622 patients.

PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Management of breast ductal carcinoma in situ in Catalonia, Spain: Results from the Grup Oncologic Calalà-Occità-Catalonia survey with 9-year follow up.

INTRODUCTION: Reliable data on DCIS incidence and management are not available in many countries. The present study describes the management of DCIS in Catalonia, Spain in the year 2005 and compares these findings to data obtained in France. Local recurrence and late toxicity rates from 2005 through the end of 2014 are reported. MATERIALS AND METHODS: Observational survey of patients with pure DCIS (n = 270) diagnosed during 2005. A written questionnaire, the same as used in the French survey, was completed by 14 doctors at 12 cancer centres in Catalonia, Spain. RESULTS: Median patient age was 55 years (range, 29-89). Diagnosis was mammographic in 225 cases (83.3%). Treatment approaches included: mastectomy (10.4% of cases), breast-conserving surgery (BCS) alone (3.7%), and BCS plus radiotherapy (RT) (85.5%). Sentinel node biopsy and axillary dissection were performed in 27.4% and 5.6% of patients, respectively. Hormonotherapy was prescribed in 45.2% of cases. Tumour nuclear grade was as follows: low (16.7% of cases), intermediate (23%), and high (55.6%). Excision was complete (margins ≥1 mm) in 75% of patients treated with BCS alone vs. 95.7% for BCS+RT. The treatment approach varied widely: mastectomy rates ranged from 7.1% to 26.7% of centres, BCS+RT from 55.5% to 87.8%, and hormonotherapy from 3.3% to 83.3%. At a median follow-up of 102.6 months, 14 patients (5.6%) presented ipsilateral breast tumour recurrence. CONCLUSIONS: These findings on DCIS management in Catalonia are consistent with previous international reports. The inter-centre differences observed are similar to those reported in other international surveys during the same period.

Incidental versus symptomatic venous thrombosis in cancer: a prospective observational study of 340 consecutive patients.

BACKGROUND: The clinical significance of incidental venous thrombosis (IVT) is uncertain. The objective of this study was to compare the clinical characteristics and the outcome of cancer patients with IVT with those of patients with symptomatic venous thrombosis (SVT). PATIENTS AND METHODS: Prospective observational study enrolling consecutive cancer patients newly diagnosed with venous thromboembolism (May 2006-April 2009). Diagnosis of IVT was based on vascular filling defects in scheduled computed tomography scans in the absence of clinical symptoms. Anticoagulant therapy was routinely prescribed regardless of SVT or IVT. RESULTS: IVT was diagnosed in 94 out of 340 (28%) patients. Patients with IVT were older (63.7 ± 10.5 versus 60.8 ± 10.5 years, P = 0.035), more frequently had metastatic cancer (82% versus 65%, P = 0.01) and were less likely to be receiving chemotherapy at the time of the thrombotic event (53% versus 67%, P = 0.018). Mean follow-up was 477 days. A lower risk of venous rethromboses was observed in patients with IVT (log-rank P = 0.043), with no differences in major bleeding and overall survival compared with SVT patients. CONCLUSIONS: A high proportion of venous thrombotic events in cancer patients are diagnosed incidentally during scheduled imaging. Prospective controlled trials evaluating the optimal therapy in this setting are required.

Brain nodules with lung mass: are they always metastases?

In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment (AU)

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Clinical axillary recurrence after sentinel node biopsy in breast cancer: a follow-up study of 220 patients.

PURPOSE: The aim of this study was to evaluate the frequency of false-negative (FN) sentinel node procedures in patients with breast cancer and the subsequent clinical outcome in such patients. METHODS: A total of 325 breast cancer patients underwent sentinel lymph node biopsy at our institution between June 1998 and May 2004. A 2-day protocol was used to localise the sentinel node with the injection of 99mTc-nanocolloid. There were two phases in the study: the learning phase (105 patients) and the application phase (220 patients). In the learning phase, a complete lymphadenectomy was always performed. In the application phase, sentinel nodes were studied intraoperatively and lymphadenectomy was performed when considered warranted by the pathological intraoperative results. RESULTS: The median follow-up duration in the 220 patients studied during the application phase was 21.2 months (range 4-45 months). In this phase a total of 427 sentinel nodes were obtained (range 1-5 per patient, median 1.99), with 66 positive sentinel nodes in 56 patients (26%). The lymphadenectomies performed were also positive in 25% of cases (14 patients). We observed a total of two false-negative sentinel lymph node results (3.45%). One of them was found during the surgical excision of non-sentinel nodes, and the other presented as an axillary recurrence 17 months postoperatively (1.72% clinical false-negative rate). The latter patient died 1 year after the first recurrence. CONCLUSION: After a median follow-up of 21.2 months we observed only one clinical recurrence among 220 patients. Our results indicate that adequate local control is achieved by application of the sentinel node protocol.

Prospective evaluation of CEA and CA 15.3 in patients with locoregional breast cancer.

The tumor markers, CEA and CA 15.3, were prospectively studied in the sera of 1057 untreated patients with locoregional breast cancer diagnosed from 1983 to 2001. Abnormal CEA and CA 15.3 serum levels were found in 13% and 18.8% of the patients, respectively. One tumor marker or another was abnormal in 22.8% of the patients. Both tumor markers were correlated with tumor size and nodal involvement, with significantly higher concentrations in patients with larger tumors or in patients with nodal involvement. CEA was also related to the histological type and CA 15.3 with the histological grade. Univariate prognostic evaluation showed that tumor size, nodal involvement, histological grade, steroid receptors, adjuvant treatment, CEA, CA 15.3 and treatment before surgery were prognostic factors in both disease-free survival (DFS) and overall survival (OS). Similar results were obtained in node-positive patients, with the same factors being prognostic, excluding adjuvant treatment and CA 15.3, in both DFS and OS. Multivariate analysis showed that tumor size, nodal involvement, histological grade, ER and CEA were independent prognostic factors in both DFS and OS in the whole group as well as in node-positive patients. In contrast, tumor size was the only useful parameter in the prognosis of node-negative patients. CA 15.3 was useful for prognosis (OS) in node-negative patients. In summary, tumor markers are useful tools in the prognostic evaluation of patients with breast cancer.

Prospective evaluation of tumor markers (c-erbB-2 oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer.

Tumor markers were prospectively (CEA and CA 15.3) or retrospectively (c-erbB-2) studied in the sera of 503 untreated patients with breast cancer diagnosed from 1988 to 2001. Abnormal c-erbB-2 levels (> 15 U/ml) were found in 7%, CEA in 12% and CA 15.3 in 13% of the 503 patients. C-erbB-2 serum levels were only related to c-erbB-2 in tissue, with significantly higher concentrations in patients with positivity in tissue. All the tumor markers (c-erbB-2 only in patients with positivity in tissue) were correlated with tumor size, TNM and nodal involvement. CEA was also related to menopausal status, c-erbB-2 overexpression in tissue and ER. Univariate analysis (mean follow-up 8 years) showed that CEA and CA 15.3 were prognostic factors with significantly shorter disease-free survival (DFS) and overall survival (OS) in patients with pretreatment tumor marker positivity. Multivariate analysis in DFS and in OS showed that nodal involvement CEA and ER but not tumor size, menopausal status, histological grade, histology, CA 15.3, c-erbB-2, PgR, adjuvant treatment, p53 (345 patients) or c-erbB-2 in tissue are independent prognostic factors. In summary, tumor markers are a useful, inexpensive and reproducible tool for prognosis in breast cancer.

C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients.

UNLABELLED: C-erbB-2, CEA and CA 15.3 serial serum determinations were performed in 250 patients (follow-up: 1-4 years, mean 2.5 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Ninety-five patients developed metastases during follow-up. RESULTS: Abnormal c-erbB-2, CEA and CA 15.3 serum levels (> 20 U/ml, > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis were found in 28.4%, 31.6% and 46.3% of the 95 patients with recurrence, with a lead time of 4.2 +/- 2.4, 5.0 +/- 2.5 and 4.6 +/- 2.7 months, respectively. One of the tumor markers was the first sign of recurrence in 69.5% of the patients. Tumor marker specificity was 100% with levels lower than the cut-point in all 155 patients without recurrence. Tumor marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver or bone metastases. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (10/12, 83.3%) than in those without overexpression (1/34, 2.9%) (p = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PgR+ patients (CA 15.3) or in PgR- patients (C-erbB-2) (p < 0.015). In conclusion, tumor markers are useful tools for the early diagnosis of metastases, being the first sign of recurrence in 69.5% of patients with relapse (76.3% in patients with metastases).

Carcinoembryonic antigen in tissue and serum from breast cancer patients relationship with steroid receptors and clinical applications in the prognosis and early diagnosis of relapse.

From July 1982 to August 1994, CEA levels were determined in 298 mammary tissue samples (30 benign, 242 primary breast cancer and 26 metastatic breast cancer). CEA serum levels were also evaluated in 30 patients with benign diseases, 153 patients with primary breast cancer and 26 patients with metastases. CEA tissue levels in both pellet and cytosol were significantly higher in samples from cancerous than from non malignant tissues (p < 0.0001), and higher in the pellet than in the cytosol (p < 0.0001). CEA in the pellet and cytosol were related to steroid receptors, with the highest levels being observed in ER+/PR+ tumors (p < 0.001). They were, however, not related to other pathological parameters such as tumor size or nodes. There was a correlation between CEA pellet and CEA serum in both patients with primary or metastatic tumors, with significantly higher CEA serum levels in patients with CEA pellet positivity than in those with CEA pellet negativity. CEA serum levels were a prognostic factor (DFS and OS) in the whole group as well as in node-positive and node-negative breast cancer patients. This prognostic value was only found in patients with CEA pellet positivity. In the follow-up of 143 NED patients, abnormal CEA serum levels rose prior to the diagnosis of relapse in 73% (29/40) of CEA pellet+ patients with distant recurrences but in only 9% (2/22) of CEA pellet- cases (p < 0.0001). In summary, CEA evaluation in tissue improves the CEA clinical application, selecting those patients whose serum CEA will be useful in the prognosis and early diagnosis of recurrence.

Impact of radiotherapy on local control and survival in uterine sarcomas: a retrospective study from the Grup Oncologic Català-Occità.

PURPOSE: In order to provide more information for the clinician and to analyze the impact of radiation therapy on the loco-regional disease-free interval (LRFI), disease-free interval (DFI) and specific overall survival (OS), a multicentric retrospective study of uterine sarcomas has been undertaken using cases reported to the Grup Oncològic Català-Occità (GOCO). PATIENTS AND METHODS: One hundred three patients were selected for this study with a median follow-up period of 49 months. Patients were restaged using the FIGO classification for endometrial adenocarcinoma. Radiotherapy was administered postoperatively to the entire pelvis in 52% of cases (54/103) and was combined with brachytherapy in 24 patients. Mean given dose was 48 Gy, with a 95% confidence interval of 45 to 50 Gy. Variables have been tested for homogeneity between hospitals. Univariate and multivariate analyses have also been carried out. RESULTS: Mean age of the selected patients was 59 years (range 35-84). Stages were distributed as follows: 66 patients (64%) in Stage I; 16 in Stage II (15.5%); 12 in Stage III (11.5%); 9 patients in Stage IVa (9%). Pathological distribution was 41.5% leiomyosarcoma, 39% mixed Mullerian tumours, 16.5% stromal sarcomas, and 2.9% of a miscellaneous group. Overall survival for the entire group was 63.7% and 56% at 2 and 5 years, respectively. Probability of LRFI reached 59.8% at 2 years and 57.4 at 5 years. The DFI at 2 and 5 years were 52.9 % and 48.7%, respectively. The LRFI probability was 41% and 36% at 2 and 5 years, respectively, without radiotherapy and reached 76% at 2 and 5 years among those patients treated with radiotherapy. There was also an increase in DFI probability because of the effect of radiotherapy, from 35% to 68.5% and from 33% to 53% at 2 and 5 years, respectively. The overall survival probability for patients treated with radiotherapy was 76% and 73% at 2 and 5 years, respectively and 51% at 2 years and 37% at 5 years without radiotherapy. Multivariate analysis demonstrated that radiotherapy improved LRFI, DFI, and overall survival. CONCLUSION: We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on loco-regional and disease-free progression intervals and survival.

Adenoid cystic carcinoma of the breast: mammographic appearance and pathologic correlation.

OBJECTIVE: The objective of our study was to describe the mammographic features of adenoid cystic carcinoma of the breast and to correlate mammography findings with histopathologic findings. CONCLUSION: Adenoid cystic carcinoma is a rare type of breast neoplasm that usually appears as a slowly enlarging nodule. In spite of its low incidence, recognition is important because early detection ensures good prognosis. On mammography, these tumors often appear as moderately circumscribed, lobulated nodules that are similar to other types of benign and malignant tumors. Therefore, cytologic and histologic evaluations are needed for accurate diagnosis.

c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value.

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 healthy subjects, 58 patients with benign breast diseases, and 413 patients with breast cancer (186 locoregional, 185 with advanced disease, and 42 with no evidence of disease). Using 15 U/ml as the cut-off, no healthy subjects or patients with benign diseases and only 2.4% of no evidence of disease patients had elevated serum levels. Abnormal c-erbB-2 levels were found in 29% (101/370) of the patients with breast carcinoma (locoregional 9%, metastases 45.4%). CEA (cut-off 5 U/ml) and CA 15.3 (cut-off 35 U/ml) sensitivity was 18% and 16% in patients with locoregional disease and 61% and 70% in those patients with advanced disease, respectively. A trend toward higher serum levels of all three tumor markers in patients with nodal involvement or greater tumor size was found, but was statistically significant only with CEA (p < 0.01). By contrast, c-erbB-2 was related to steroid receptors, in both locoregional and metastatic tumors. When the prognostic value of these markers was evaluated, patients with abnormally high presurgical CEA and c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative (p < 0.05 and p < 0.001, respectively) and node-positive patients (p < 0.556 and p < 0.001, respectively). By contrast, no relationship was found between CA 15.3 values and prognosis. Multivariate analysis showed that CEA and c-erbB-2 were also prognostic factors. The correlation between serum and tissue levels of c-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). Serum concentrations in patients with advanced disease were related to the site of recurrence, with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum levels seem to be a useful tumor marker in the prognosis of patients with breast cancer. Using all three tumor markers, sensitivity was 35% in patients with locoregional breast cancer and 88% in patients with recurrence.

Primary small cell carcinoma of the esophagus: a review of the literature with emphasis on therapy and prognosis.

BACKGROUND: Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. METHODS: The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. RESULTS: The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P < 0.0001). The median survival was 8 months for patients with LS and 3 months for those with ES. Univariate analysis of LS showed 3 significant prognostic factors: age (for patients age < or =60 years, the median survival was 11 months, whereas for those age >60 years, the median survival was 6 months), tumor size (for those with tumors < or =5 cm, the median survival was 12 months, whereas for those with tumors >5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. CONCLUSIONS: Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors.

Simulation by a diagnostic CT for the early vocal cord carcinoma.

The CT-based simulation with a 3D planning system permits the optimization of radiotherapy treatments. The goal is to obtain an increase in the local control and survival with a reduction of the treatment related toxicity. In our hospital, we do not have a CT simulator and our 3D planning system is not yet working, therefore, we have developed a system to simulate radiotherapy treatments using a diagnostic CT. We began by simulating an early vocal cord carcinoma. The rules of this simulation are presented using a clinical case as an example.

Radiotherapy in the maxillary hemangioma.

We present the case of a large maxillary hemangioma treated by radiotherapy. Only 4 cases managed by radiotherapy have been reported in the literature, and most authors negate the radiosensitivity of the tumor. In our patient, the outcome was excellent; by 6 months tumor reduction was more than 50%. This is the first case referred to in the literature whose radiotherapy response was evaluated by magnetic resonance imaging. We describe the clinical and imaging findings of this very rare tumor and its evolution. We also comment on the literature reviewed.

Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3.

To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3 in the early diagnosis of recurrence, serial serum determinations of these antigens were performed in 200 patients (follow-up 1-4 years, mean 2.2 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA 15.3 were elevated (> 20 U ml-1, > 10 ng ml-1 or > 60 U ml-1 respectively) before diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead time of 4.5 +/- 2.4, 4.9 +/- 2.4 and 4.8 +/- 2.4 months respectively. Tumour marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver metastases. When patients with locoregional recurrences were excluded, sensitivity improved: 31% (c-erbB-2), 33% (CEA) and 56% (CA 15.3), with 76% having at least one of the three tumour markers. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PR+ patients (CA 15.3, P < 0.0001) or in PR- patients (c-erbB-2, P = 0.009). Specificity of the tumour markers was 100% for all three markers (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis of metastases, mainly in those patients with c-erbB-2 overexpression in tissue. Using all three markers simultaneously it is possible to increase the sensitivity in the early diagnosis of recurrence by 11.2%.

C-erbB-2 oncoprotein in the sera and tissue of patients with breast cancer. Utility in prognosis.

C-erbB-2 serum levels were studied in the sera of 50 healthy subjects, 56 patients with benign breast diseases and 412 patients with breast cancer. Using 15 U/ml as the cut-off, no healthy subjects, patients with benign disease and only 2.4% of patients with no-evidence of disease had serum levels higher than this cut-off point. Abnormal c-erbB-2 levels were found in 9.2% of the patients with locoregional breast carcinoma and in 45.4% of those with advanced disease. C-erbB-2 serum levels in patients with locoregional breast cancer were not related to tumor size or nodal involvement. By contrast, significantly higher c-erbB-2 serum levels were found in ER- or PgR- tumors than in those ER+ or PgR+ tumors, in both locoregional or metastatic tumors. The correlation between serum and tissue levels of C-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). In patients with C-erbB-2 overexpression in tissue, c-erbB-2 serum levels were related to tumor size and nodes, with higher values in tumors greater than 5 cm or in those with more than 3 nodes involved. When the prognostic value of this oncoprotein was evaluated, patients with abnormally high presurgical c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative and node-positive patients. Serum concentrations in patients with advanced disease, were related to the site of recurrence with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum level seem to be a useful tumor marker in the prognosis of patients with breast cancer.

Six-year follow-up of primary small cell carcinoma of the esophagus showing a complete response: a case report.

Six-year follow-up of a case of small cell carcinoma of the esophagus showing a complete response is reported. The small cell pattern appeared intermingled with areas of invasive squamous cell carcinoma and carcinoma in situ. A neoadjuvant polychemotherapy regimen was used, followed by radiation therapy and adjuvant chemotherapy. This therapeutic combination resulted in complete response of the disease, as confirmed by computed tomography, endoscopy and biopsy. The patient is currently still alive, 6 years after the diagnosis, without any sign of relapse. A review of the literature reveals that this patient has survived longer than any others with this disease after treatment by chemoradiotherapy. The authors suggest that this therapy should be considered for patients with limited small cell carcinoma of the esophagus.