Local-regional Disease Research Articles

Tumor Distribution and Survival in Six Patients with Brain Metastases from Cervical Carcinoma

Objective. The aim of this study was to investigate the patterns of brain involvement and the outcome of patients with brain metastases from cervical carcinoma.Methods. Between January 1982 and November 1999, 1279 patients with brain metastases were treated at the Cleveland Clinic. Six of them had brain metastases from cervical carcinoma. We retrospectively reviewed the patient and tumor characteristics at the time of the primary diagnosis as well as at the time of the brain metastases diagnosis.Results. Brain metastases from cervical carcinoma were rarely accompanied by systemic disease, but they were commonly accompanied by uncontrolled local–regional disease. The median interval from the appearance of the primary carcinoma to the detection of brain metastases in 5 patients was 12 months. Multiple brain lesions developed in 4 of 6 patients and consisted of multiple tumors distributed in the cerebral hemispheres (2 patients) or both the cerebral and the cerebellar hemispheres (2 patients). Only 2 patients had a single lesion confined to a cerebral hemisphere. One patient was treated with stereotactic radiosurgery alone, 3 with surgery followed by whole brain radiation therapy, 1 with whole brain radiotherapy, and 1 each with whole brain radiotherapy and stereotactic radiosurgery. Patients treated with surgery had a median survival of 8.25 months, while patients treated with whole brain radiotherapy with or without stereotactic radiosurgery had a median survival of 3.75 months. The 1 patient treated with stereotactic radiosurgery alone survived for 22.5 months.Conclusion. Although the number of the patients was too small to detect definitive patterns of brain metastases from cervical carcinoma, the results of our review suggest that, in contrast to previous reports, extended survival can occur with more aggressive treatment such as surgery or stereotactic radiosurgery.

Synovial sarcoma in children: surgical lessons from a single institution and review of the literature

BACKGROUND: Synovial sarcomas are malignant high-grade, soft-tissue neoplasms that account for 7% to 8% of all malignant soft-tissue tumors and are the most common nonrhabdomyosarcoma soft-tissue sarcomas in pediatric patients. STUDY DESIGN: A retrospective review of the records of children younger than 17 years with synovial sarcoma treated at the University of Texas MD Anderson Cancer Center from 1966 until 1999 was undertaken. Primary site, tumor size, tumor margins, surgical treatment, adjuvant therapy, local and distant recurrence, and survival were recorded for 42 patients. Overall survival (OS) and progression-free survival (PFS) rates were calculated by the Kaplan-Meier method. The PFS and OS comparisons were performed using the log-rank test. RESULTS: Forty-four patients were identified, but two patients were excluded because of incomplete records. The median followup duration for the 42 patients was 8.8 years (range 0.2 to 22.4 years). The 5-year progression-free survival and overall survival rates were 75.6% and 87.7%, respectively. Eleven patients were dead and four others had progressed but were alive without evidence of disease after further therapy. Intergroup Rhabdomyosarcoma Study (IRS) grouping and tumor invasiveness were found to be significant prognostic indicators (p < 0.01 and p = 0.02, respectively). Patients with initial gross total resection (IRS Groups I and II) and noninvasive tumors (T1) were most likely to have prolonged PFS and OS. Patients with small tumors (< 5 cm) (p = 0.09) had better PFS and OS. Adjuvant radiation therapy appeared to be of benefit, and chemotherapy did not seem to impact PFS or OS. Tumors ≥ 5 cm are associated with increased risk of local recurrence and distant metastases. CONCLUSIONS: Complete resection with clear, yet not necessarily large, margins remains the treatment of choice for synovial sarcoma in children. Adjuvant radiation therapy should possibly be considered in patients with clear margins (IRS Group I) and in patients with microscopic residual tumor (IRS Group II). Chemotherapy did not seem to impact PFS or OS. Lymph nodes should be evaluated for local regional disease.

Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck

Background: Results with docetaxel as single drug in squamouscell head and neck cancer have been encouraging. The purpose of the present phase II study is to evaluate the antitumour efficacy and toxicity of the combination of docetaxel and cisplatin in patients with recurrent or disseminated squamouscell carcinoma of the head and neck (SCCHN) for whom no curative therapy is available.Patients and methods: Eligibility criteria included: written informed consent; WHO performance status ≤2; age 18–70 years; adequate bone marrow, liver, and renal function; measurable or evaluable disease; no previous systemic chemotherapy (prior radiotherapy and/or surgery were allowed); no other previous or concurrent malignancy; no peripheral neuropathy. Treatment consisted of docetaxel 75 mg/m2 in a one-hour infusion after pre-treatment with prednisolone, followed by cisplatin 75 mg/m2 in a half-hour infusion preceded and followed by hydration. Treatment was repeated every three weeks for a maximum of eight cycles.Results: Twenty-five patients (median age 52 years, range 33–66) entered the trial, all were evaluable for survival, twenty-four for response and toxicity. Twenty-four patients had under-gone prior radiotherapy and seventeen had also had surgery. Nineteen had local-regional recurrence only, three had local-regional disease and distant metastases, and three had distant metastases only. Patients received a median of 5 treatment cycles (range 2–8). Overall response rate was 33% (8 of 24) of patients; complete response rate was 8% (2 of 24) of patients, lasting 2.2 and 17.1 months, respectively; partial response rate was 25% (6 of 24) of patients, lasting for a median of 4.9 months (range 1.7–11.6 months). Median survival was 11 months. Toxicity was relatively well tolerated. However, one patient died of probable toxicity (neutropenia and infection) and three patients discontinued treatment because of toxicity (massive oedema, myocardial infarction, persistent thrombo-cytopenia). The most frequent moderate-to-severe toxicity (75% of patients) was grade 3–4 neutropenia, transient in all but one patient. Grade 3 neuropathy occurred in one patient, none had grade 4. Grade 3 oral mucositis occurred in three patients, none had grade 4. Grade 2–3 hypomagnesaemia occurred in 10 patients requiring magnesium infusion.Conclusions: Docetaxel and cisplatin is an active combination in patients with recurrent or disseminated SCCHN. Remissions are however fairly short. Toxicity is significant, but generally manageable.

Clonal heterogeneity and evolution of tumor DNA ploidy in neuroblastoma (NB) presenting as local-regional (LR) disease

Clonal heterogeneity and evolution of tumor DNA ploidy in neuroblastoma (NB) presenting as local-regional (LR) disease

Unresectable primary and recurrent head and neck tumors: effect of hyperthermia and carboplatin--preliminary experience.

To perform a single-arm study to determine the effectiveness of and potential toxic reactions to local hyperthermia and systemic carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II) for the treatment of advanced or recurrent squamous cell carcinomas of the head and neck. Eight patients with squamous cell carcinoma of the head and neck and stage IV disease (N2 or N3 neck adenopathy) or recurrent local-regional disease and who were previously and definitively treated were included in the study. Thermochemotherapy was administered every 4 weeks. Recorded end points were tumor response, duration of response, incidence of distant metastases, survival, cause of death, and toxic reactions. One patient had a complete response to therapy, and two had a partial response. Five patients had no response or developed progressive disease during therapy. Six patients died after 4-13 months of progressive disease. Two long-term survivors received radiation therapy; one also underwent surgical resection for residual neck disease. Each thermochemotherapeutic session was well tolerated, with minimal discomfort. Toxic reactions included hypotension, vomiting, hyponatremia, anemia, thrombocytopenia, and infection at the site of administration. There were no life-threatening toxic reactions. The combined use of hyperthermia and carboplatin shows potential in the management of unresectable head and neck tumors and is safe and well tolerated. Further studies on thermochemotherapy are warranted to assess its potential.

Present and future of sentinel node lymphadenectomy in breast cancer.

Up to about 1960, it was generally thought that breast cancer was mainly a local-regional disease. This concept, inherited from Halsted, led to increasingly aggressive treatments of the primary lesion and the regional lymph nodes. Total mastectomy, which in the form developed by Halsted was already an extensive operation, became enlarged to include extensive removal of skin and use of skin transplants, sacrifice of important vessels and nerves such as the thoracodorsals, and meticulous dissection of the regional nodes, sometimes including those of the internal mammary chain via thoracotomy. Radiotherapy was given to the axillary, supraclavicular and retrosternal lymph node areas, as well as to the mastectomy scar.

New treatment possibilities for pancreatic and biliary tumours.

Pancreatic adenocarcinoma is one of the most lethal cancers in the Western world with a median survival of approximately 3 months. Patient survival depends on the extent of disease and performance status at diagnosis. The extent of disease is best categorised as resectable, locally advanced or metastatic. Surgery is the only curative treatment. It is, however, an option in only 10-20% of patients. Long-term survival after surgical resection of pancreatic cancer is less than 20%. Local recurrence occurs in up to 85% of patients who undergo surgery alone. Local-regional tumour control is maximised with combined modality therapy in the form of chemoradiation and surgery. With improved therapy for local-regional disease, liver metastases become the predominant form of tumour recurrence and occur in 50 to 70% of patients following potential curative combined modality treatment. At the time of diagnosis, 40% of patients have locally advanced disease and more than 40% have visceral metastases, most frequently in the liver. Therefore, with new surgical and radiotherapeutic techniques improving locoregional control, we will face distant metastases being responsible for therapy failure more often and effective systemic treatment will become even more important for prolonging survival. Unfortunately results obtained with chemotherapy failed to have an important impact on the final outcome and have been the reason for scepticism among clinicians and oncologists for many years. However, a totally fatalistic approach is not justified, because a significant proportion of patients do achieve benefit from chemotherapy. Several new and innovative therapeutic modalities are in development and offer hope for an improved outcome for patients with pancreatic cancer in the future.

Consensus statement on postmastectomy radiation therapy

The potential effects of postmastectomy radiation therapy (PMRT) on local-regional disease control, systemic disease control, overall survival, and treatment-related morbidity have been the subject of many institutional reports as well as prospective randomized clinical trials, including ongoing follow-up from two well-designed trials from Denmark and British Columbia ( 1 Overgaard M. Hansen P.S. Overgaard J. et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997; 337: 949-955 Crossref PubMed Scopus (2190) Google Scholar , 2 Ragaz J. Jackson S.M. Le N. et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997; 337: 956-962 Crossref PubMed Scopus (1474) Google Scholar ). The recent presentation and publication of long-term results of these trials has generated considerable discussion regarding the current practice of PMRT in the United States.

Metaplastic breast cancer: Prognosis and response to systemic therapy

Metaplastic breast cancer is a rare disease with little information available to guide therapy. The goals of this study were to describe the patient characteristics, systemic therapies and clinical outcomes of all patients with primary metaplastic breast cancer treated at Mayo Clinic between 1976 and 1997. Patients were identified through the medical index of Mayo Clinic. Clinical information was abstracted from the medical record of each patient. A literature search using MEDLINE and CANCERLIT for the years 1966-1997 was performed to identify all previously reported case series in the English language containing 10 or more patients. Twenty-seven patients were identified with a median age at diagnosis of 59 years (range 39-90 years). The median tumor size was 3.4 cm (range 0.5-7.0 cm). One patient had metastatic disease at presentation. Twenty-three patients had information available on nodal status, estrogen receptor (ER) and progesterone receptor (PR) status. Twenty patients (87%) were node-negative and three patients (13%) were both ER and PR positive. Disease-free survival (DFS) and overall survival (OS) were assessed for those who presented with local-regional disease. The three-year DFS was 40% (95% CI: 23%-73%) and the three-year OS was 71% (95% CI: 51%-97%). In univariate analysis, those patients 60 years of age or older at diagnosis were found to have an increased DFS (P = 0.011). Among those with prior estrogen use, both DFS (P = 0.022) and OS (P = 0.003) were decreased. Thirteen patients (50%) developed metastases with a median DFS time of 2.4 years. Ten different chemotherapy regimens were utilized for metastatic disease and one partial response was observed. There were no responses to tamoxifen in four patients with metastatic disease. Median survival after the development of metastases was eight months. Despite presenting more commonly as node-negative disease, DFS and OS in metaplastic breast cancer is decreased compared to typical adenocarcinomas. Systemic therapy also appears to be less effective. Patients with metaplastic breast cancer, particularly those with metastatic disease could be appropriate candidates for innovative therapeutic regimens.

An initial experience using concurrent paclitaxel and radiation in the treatment of head and neck malignancies

Background: Combined modality therapy plays a central role in the management of head and neck malignancies. This study examined the feasibility and preliminary results of treating a group of patients using concurrent bolus paclitaxel (Taxol™) and radiation therapy.Methods: Fourteen patients with a median age of 56 years (range 42–81) were treated. Paclitaxel was given every 3 weeks at a dose of 100 mg/m2 concurrently with external beam radiation. The patients treated included those who had failed to achieve a complete response (CR) to induction chemotherapy with cisplatin, 5-fluorouracil, and leucovorin (PFL), or who had locally advanced disease not previously treated.Results: Median follow-up from the initiation of treatment is 40 months (range 23–48). The majority of patients (13/14) achieved clinical CRs at the primary site. The development of responses was characterized by a long time course. Three patients who were nonresponders (NRs) to induction PFL chemotherapy were treated. One was a clinical CR at the primary site, one did not achieve a CR, and the other had residual disease in the neck. Four patients have failed, one with local-regional disease, one with a marginal failure, one with distant metastases, and one was not rendered disease-free by the treatment. As expected, significant local toxicity was observed. Most patients were managed with the aid of a percutaneous endoscopic gastrostomy (PEG). Two patients experienced significant moist desquamation and required treatment breaks of greater than 1 week.Conclusion: Paclitaxel can be given on a 3-week schedule at 100 mg/m2 concurrently with radiation. The preliminary results indicate good local responses and acceptable toxicity. This treatment approach merits further study in the treatment of head and neck malignancies, and should be considered as an option in other sites.

CLASSIFICATION AND STAGING OF MELANOMA

Although a standardized and uniformly accepted cancer staging system is an essential and fundamental requirement to enable meaningful comparisons across patient populations, the sometimes capricious biologic behavior of melanoma makes developing such a staging system particularly difficult. Since the earliest well-documented attempts at classifying patients with cutaneous melanoma were described more than 50 years ago, the identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. The current AJCC staging system is based on relatively well-established prognostic factors; however, several recent reports have identified additional prognostic factors not included in the current system, and other studies support the re-evaluation of some of the currently employed staging criteria. Some of the more controversial areas include the relevance of level of invasion versus tumor thickness, optimal cutoffs for tumor thickness, importance of ulceration, the grouping of satellites with in-transit metastases, the inclusion of microsatellites and local recurrences as a separate staging criterion, the replacement of size of nodal mass with number of positive nodes, the importance of nodal metastases in more than one nodal basin, and the prognostic significance of distant metastases. Therefore, future modifications of the staging system are anticipated to better incorporate these observations. Stage-specific staging recommendations for the patient with melanoma provide the clinician with a framework to most efficiently assess extent of disease in an era of cost-conscious clinical practice. In the asymptomatic patient with primary melanoma (stage I or II), we recommend a chest roentgenogram and evaluation of alkaline phosphatase and LDH levels; extensive radiologic evaluations are not indicated, because the rate of detection in this population is extremely low. Additional staging information should also be obtained by the technique of lymphatic mapping and sentinel lymphadenectomy. For patients with local-regional disease (stage III, satellites, and local recurrence), a selective approach to imaging studies is warranted. For this patient population, we recommend complete blood count, liver function tests including alkaline phosphatase and LDH, a chest roentgenogram, and a CT scan of the abdomen. Although the yield of these tests, particularly CT of the abdomen, in detecting distant metastases in asymptomatic patients is low, they may identify false-positive abnormalities and provide an important baseline for future studies in this high-risk population. For patients with disease below the waist or in the head and neck region, we recommend CT of the pelvis and CT of the neck, respectively. Additional studies should be done only if clinically indicated. Finally, patients with known systemic disease (stage IV) should be more comprehensively evaluated, because the likelihood of detecting asymptomatic metastases is higher. Accordingly, in addition to the work-up outlined previously for stage III patients, we also perform a CT scan of the chest and MR imaging of the brain; other studies (e.g., bone scan, gastrointestinal series) are performed on the basis of symptoms.

Adjuvant Radiotherapy for Squamous Cell Carcinoma of the Tongue Base: Improved Local-Regional Disease Control Compared with Surgery Alone

Purpose: The purpose of this retrospective study is to present the results of postoperative adjuvant radiotherapy after primary surgery for squamous cell carcinoma of the tongue base and to compare these results to those obtained with surgery alone. Methods: Between 1974 and 1993, continuous-course postoperative radiotherapy was delivered to 24 patients (Adjuvant Radiotherapy Group). Results were compared to those from a group of 55 patients treated with surgery alone (Surgery Group). Results: Characteristics of the two groups were similar, except that a larger proportion of patients in the Adjuvant Radiotherapy Group had higher pathologic TNM stages. Ipsilateral neck control (87% vs. 68%, p = 0.04), contralateral neck control (100% vs. 76%, p = 0.002), relapse-free survival (64% vs. 46%, p = 0.04), and control above the clavicles (80% vs. 48%, p = 0.007) were significantly higher in the Adjuvant Radiotherapy Group compared to those in the Surgery Group (5-year figures shown). Conclusion: The use of adjuvant radiotherapy after surgical resection of tongue base squamous cell carcinoma significantly decreased the rate of local-regional recurrence and improved relapse-free survival compared with surgery alone but did not alter cause-specific or overall survival.

Surgical management of primary cutaneous melanomas of the hands and feet.

The purpose of the study was to investigate the surgical management of cutaneous melanomas of the hands and feet. Prior studies suggest that patients with melanomes > 1-mm thick should be treated with excision with a 2-cm margin and undergo elective lymphadenectomy in selected circumstances. These recommendations are based primarily on data from melanomas of the trunk and extremities. Melanomas of the hands and feet are less common and less well studied. They pose a surgical challenge because primary wound closure often is difficult, and the incidence and management of regional node metastases are unclear. Charts of patients with melanomas of the hands or feet treated at the Massachusetts General Hospital between 1980 and 1994 were reviewed retrospectively. Local recurrence rates and the incidence of regional node metastases were analyzed as a function of histology, margin of excision, and microscopic thickness of the melanoma. Data from 116 patients (39 men, 77 women) with melanomas of the hands (n = 26) and feet (n = 90) were evaluated. Pathologic diagnoses were: acral lentiginous melanoma (48 patients); subungual melanoma (13 patients), and skin of dorsum of the hand or foot (n = 55). Digital amputation was required in all 13 patients with subungual melanoma to maintain local control; still, nodal metastases developed in 46% of patients within 1 year. Seventy-one percent of patients with acral lentiginous melanoma presented with lesions > or = 1.5 mm, and nodes or systemic disease or both developed in 56% of patients. Acral lentiginous melanoma lesions < 1.5-mm thick were treated principally by excision with a 1-cm margin; a local recurrence or metastases did not develop in any of the patients. None of the patients with melanomas on the dorsum of the hand or foot < 1.5-mm thick had a local recurrence, but regional or systemic disease developed in > 50%. Local control in patients with lesions > 1.5-mm thick frequently required skin grafting or amputation. The majority of patients with melanomas > or = 1.5 mm in thickness undergoing elective lymph node dissection had histologically positive nodes for melanoma. Melanomas of the hands and feet < 1.5-mm thick have a low incidence of nodal metastases and are treated effectively with wide excision of the primary with a 1-cm margin. Thicker melanomas are associated with a > 50% rate of regional or systemic failure. In the absence of metastatic disease, these individuals should undergo local excision with a 2-cm margin and intraoperative lymphatic mapping followed by lymphadenectomy if the sentinel node is positive.

Tumor spread and outcome of treatment in primary esophageal small cell carcinoma.

The most effective treatment for patients with esophageal small cell carcinoma has not yet been established because of the overall extremely poor prognosis regardless of the mode of treatment. The role of esophagectomy has been controversial in the management of patients with this disease. The clinicopathologic characteristics of 13 patients with primary esophageal small cell carcinoma were retrospectively studied and the prognostic significance of various factors with respect to esophagectomy were evaluated. Lymph node metastases and distant metastases were found at the time of presentation in 92.3 and 46.2%, respectively. Two of nine patients treated by surgical resection for local-regional disease survived >5 years after radical esophagectomy with a projected 5-year survival rate of 22.2%. The remaining 4/13 patients were treated by nonsurgical modalities, but died of the disease within 10 months. A significant difference (P < 0.05) was detected between the survival curves of the two groups of patients. Radical esophagectomy may be an effective treatment modality in improving survival and the odds of a cure in patients with local-regional small cell carcinoma of the esophagus.

Significance of Family History in Breast Cancer Treated with Breast Conservation Therapy

: The purpose of this study was to evaluate the impact of family history (FH) of breast cancer on the outcome of patients with local-regional breast cancer treated with breast conservation therapy. Of 974 patients treated with breast conservation therapy, a total of 794 consecutive cases were evaluable with adequate FH data and a greater-than-1-year follow-up. All patients had local-regional disease (stages O-IIIA) and underwent lumpectomy, axillary node dissection, and radiation therapy. Seventeen percent of patients had a positive family history of breast cancer, which was defined as a first degree relative (mother, sister, daughter). A significant difference was seen in overall survival in patients with and without an FH of breast cancer (p = 0.027). While FH did not correlate with differences in local failure, distant failure, disease specific survival, or overall survival in patients less than or equal to age 50, a positive FH correlated with a worse disease specific survival (p = 0.045) and a worse overall survival (p = 0.017) in patients over age 50. Multivariate (Cox) analysis confirmed the significance of FH (p = 0.008), tumor size (p = 0.001), and nodal status (p = 0.015). Comparing patients with and without an FH, no differences were seen in age at presentation, age of menarche, age of menopause, parity, tumor size, histologic and nuclear grade, nodal status, or estrogen receptor status. In patients with an FH of breast cancer, the most commonly affected relative was the mother (9.4%). While FH did not impact on outcome of patients age 50 or younger, it was prognostic for a poorer overall survival in older patients, and poorer disease-specific survival. Patients with an FH of breast cancer are similar to patients without a family history in tumor and patient characteristics. An FH of breast cancer does not correlate with an increased local or distant failure in our study population as a whole, but does correlate with a poorer overall survival when compared to patients without an FH of breast cancer.?

Neoadjuvant therapy for upper gastrointestinal tract cancers.

Esophageal, gastric, and pancreatic cancers frequently present with extensive local regional disease, which can be difficult to resect or to definitively control with radiation therapy given as a single modality. In addition, these patients are at high risk for the development of distant metastasis. Neoadjuvant chemotherapy is a promising experimental approach for the use of combined modality treatments that involve a systemic component. The theoretical background for the use of chemotherapy followed by an operation or chemotherapy plus radiation in these tumors has been extensively described. For esophageal cancer, many phase II trials have demonstrated tolerance to systemic chemotherapy; chemotherapy plus radiation prior to operation has more toxicity. Definitive phase III studies testing the hypothesis that this approach is superior to operation alone have recently been performed in the United States and Europe. These data are currently being analyzed. For the use of combined modality therapy of chemoradiation, random assignment trials have demonstrated an improvement in cure rate for patients with squamous cell carcinomas of the esophagus. Preliminary data suggest a similar outcome for adenocarcinoma, but the number of patients who have been studied is smaller. Newer phase III studies involve the use of new systemic agents that have demonstrated activity in metastatic disease (such as paclitaxel) or the use of higher doses of radiation therapy. For gastric cancer, a substantial number of phase II trials have again demonstrated tolerance to preoperative chemotherapy with no increase in operative morbidity or mortality. Small-scale phase III trials have been performed that suggest an improvement in outcome. Definitive studies are in the planning stage. Finally, for pancreatic carcinoma, in which local control is an even more difficult issue, a major stumbling block remains the development of newer systemic therapies that have activity in this disease. The recent identification of gemcitabine as having modest activity as a single agent and its potential use with radiation therapy is being explored in the neoadjuvant setting.

Expression of the oncogene c-erbB-2 in canine mammary cancers and tumor-derived cell lines

Abstract Objective To determine, for canine mammary tumors, whether malignancy, with or without local invasion or regional metastasis, was associated with overexpression of the oncogene c-erbB-2. Design c-erbB-2 expression was measured in canine mammary tumor-derived cell lines and in mammary tumor tissues from clinical cases. Clinical samples were examined histologically to determine whether they were benign or malignant and, if malignant, whether they had evidence of local invasion or regional metastasis. Canine fibroblast cultures and normal canine mammary epithelial tissues were used as reference standards for cell lines and mammary tumors, respectively. Sample Populations 28 canine mammary tumor tissue samples obtained surgically from clinical cases and samples from 7 canine mammary tumor cell lines derived from primary canine mammary tumors. Procedure c-erbB-2 mRNA levels were determined by means of hybridization of total polysomal RNA with a 32P-labeled human c-erbB-2 probe on dot blots, and results were quantified by means of scanning densitometry. Overexpression of c-erbB-2 was defined as an autoradiographic density ≥ 2 times the density of reference samples on the same blot. Results Overexpression of c-erbB-2 was detected in 17 of 23 malignant tumors, 0 of 5 benign tumors, and 2 of 7 mammary tumor cell lines. c-erbB-2 overexpression was correlated with a histopathologic diagnosis of malignancy (P= 0.005) but not with the presence of local invasion or regional metastatic disease (P = 0.621). Conclusions Results suggest that overexpression of c-erbB-2 occurs prior to the development of metastatic disease in canine mammary tumors and plays a role in the development of malignancy. (Am J Vet Res 1996; 57:693–696)

Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head

Local recurrence in the bed of the resected pancreas is the most common site of tumor recurrence following a standard pancreaticoduodenectomy (PD) for adenocarcinoma of the pancreatic head. In an attempt to improve local and regional disease control and thereby enhance the quality and length of survival in patients undergoing potentially curative PD, we have used a protocol of preoperative multimodality therapy. All patients were treated with external-beam radiation (30.0 or 50.4 Gy) and concomitant 5-fluorouracil (300 mg/m2 per day) prior to PD. Electron-beam intraoperative radiation therapy was given to the bed of the resected pancreas before reconstruction. Patients were assessed for recurrence by physical examination, chest roentgenography, and computed tomography scan performed at 3-month intervals following treatment. Thirty-nine patients completed all therapy; 1 perioperative death occurred. Thirty-eight tumor recurrences have been documented in 29 patients at a median of 11 months from the date of diagnosis; 23 patients died of disease. The liver was the most frequent site of recurrence, and liver metastases were a component of treatment failure in 53% of patients. Isolated local or peritoneal recurrences were documented in only 4 patients (11%). The only significant clinical or pathologic variable predictive of local-regional recurrence was a previous laparotomy and intraoperative biopsy. The median survival of all 39 patients was 19 months, and the 4-year actuarial survival rate was 19%. Preoperative chemoradiation, PD, and electron-beam intraoperative radiation therapy for adenocarcinoma of the pancreatic head have resulted in improved local-regional tumor control, with distant metastatic disease becoming the predominant site of tumor recurrence. Future treatment strategies should incorporate effective multimodality therapy for local-regional disease as demonstrated in this study. Major improvements in overall survival will likely await the development of systemic or regional therapy for liver metastases.

The tumor voluem and clonogen number relationship: Tumor control predictions based upon tumor volume estimates derived from computed tomography

Purpose : While tumor volume is an important parameter predicting clinical outcome, its relationship to clonogen number remains uncertain. This uncertainty is related to many factors, among them treatment response heterogeneity, which obscures the influence of patient and treatment-related parameters. In this study, we analyze the effect of tumor volume on local and regional recurrence in a setting tightly controlled for dose, treatment time, and patient selection. The hypothesis that changes in clonogen number scale directly with changes in tumor volume is tested. Methods and Materials : Using digital reconstruction of diagnostic computed tomography (CT) scans, primary and total tumor volumes were estimated in 51 cases of advanced squamous cell carcinoma of the head and neck. All patients were managed with a concomitant boost accelerated superfractionated schedule to a median dose of 70.2 Gy. Clinical data were fitted to a mixture model to relate tumor volume parameters to control probability where volume and clonogen number were related by the relationship m = a · V b , where m is initial clonogen nubmer, a is a proportionality constant, V is tumor volume, and b is the volume exponent. Results : Tumor volume estimates for primary tumor ranged from 3–196 cm 3 and for total tumor volume 5–196 cm 3. Actuarial local-regional control is 63%. The estimated volume exponent b is 0.85 (95%, confidence interval (c.i.): 0.40 – 1.29) for primary tumor volume and 1.1 (95%, c.i.: 0.33 – 1.85) for total tumor volume. Conclusion : This study quantifies the e adverse influence of tumor volume on local-regional disease control in advanced head and neck cancer. The derived volume exponent approximates to one, the theoretcal expectation if the growth fraction is roughly constant and clonogen number increases linearly with volume. Finally, these results suggest that radiobiological parameters are more reliably estimated from clinical data with narrowly define strata.

Role of computed tomography in the staging of patients with local-regional metastases of melanoma.

To determine the value of computed tomographic (CT) scans in the staging of asymptomatic melanoma patients who presented with or developed local-regional disease as the first site of recurrence and had both a normal chest radiograph and serum lactate dehydrogenase (LDH) level. The records of 99 patients with local-regional disease were reviewed. Of these, 89 met the study criteria and are the subjects of this analysis. Radiologic findings were categorized into the following four groups: (1) true-positive (TP), when the scan identified either regional or distant disease that was not appreciated on physical examination; (2) false-positive (FP), when the scan showed a radiologic abnormality that either did not change for at least 6 months or was proven to be histologically benign; (3) false-negative (FN), when a patient had symptoms suggestive of or suspicious for metastases and was subsequently found to have metastases, but all imaging studies were nondiagnostic; and (4) true-negative (TN), when all imaging studies were negative for metastases in an asymptomatic patient. Findings on CT scan were TP for six patients (7%), FP for 20 (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest identified disease that was not visible on chest radiograph in only one and CT of the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging (MRI) of the brain showed no evidence of brain metastases in any patient, although it showed asymptomatic skull metastases in one patient. The most common FP findings were hypodense hepatic lesions and noncalcified lung nodules. TP findings are observed in approximately 7% of patients with local-regional disease, which indicates a low yield but definite usefulness of CT scans in this subset of patients. Because FP are more common than TP findings, histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is not necessary in asymptomatic patients. CT of the chest adds little to a chest radiograph. In light of today's more cost-conscious health-care environment, our results are of practical importance.