Bruce G. Haffty

Adenoid cystic carcinoma : A retrospective clinical review

Adenoid cystic carcinoma (ACC) are uncommon tumors, representing about 10% to 15% of head and neck tumors. We compare the survival and control rates at our institution with those reported in the literature, and examine putative predictors of outcome. All patients registered with the tumor registry as having had ACC were identified. Demographic and survival variables were retrieved from the database. Additionally, a chart review of all patients was done to obtain specific information. Minor gland tumors were staged using the American Joint Committee on Cancers criteria for squamous cell carcinomas in identical sites. Histopathologic variables retrieved included grade of the tumor, margins, and perineural invasion. Treatment modalities, field sizes, and radiation doses were recorded in applicable cases. An effort to retrieve archival tumor specimens for immunohistochemical analysis was undertaken. A total of 69 patients were treated for ACC from 1955 to 1999. One patient, who presented with fatal brain metastasis, was excluded from further analysis. Of the remaining 68 patients, 30 were men and 38 were women. The average age at diagnosis was 52 years, and mean follow‐up was 13.2 years. Mean survival was 7.7 years. Overall survival (OS) rates at 5, 10, and 15 years were 72%, 44%, and 34%, and cause‐specific survival was 83%, 71%, and 55%, respectively. Recurrence‐free survival rates were 65%, 52%, and 30% at 5, 10, and 15 years, with a total of 29 of 68 (43%) eventually suffering a recurrence. Overall survival was adversely affected by advancing T and AJCC stage. Higher tumor grades were also associated with decreased OS, although the numbers compared were small. Primaries of the nasosinal region fared poorly when compared with other locations. Total recurrence‐free survival, local and distant recurrence rates were distinctly better in primaries of the oral cavity/oropharynx when compared with those in other locations. Reduced distant recurrence‐free survival was significantly associated with increasing stage. No other variables were predictive for recurrence. Additionally, we found that nasosinal tumors were more likely to display higher stage at presentation, and were more often associated with perineural invasion. Also of interest was the association of perineural invasion with margin status, with 15 of 20 patients with positive margins displaying perineural invasion, while only 5 of 17 with negative margins showed nerve invasion (P = 0.02). On immunohistochemistry, 2 cases of the 29 (7%) tumor specimens found displayed HER‐2/neu positivity. No correlation between clinical behavior and positive staining could be demonstrated. Our data concur with previous reports on ACC in terms of survival and recurrence statistics. Stage and site of primary were important determinants of outcome. Grade may still serve a role in decision making. We could not demonstrate any differences attributable to primary modality of therapy, perhaps due to the nonrandomization of patients into the various treatment tracks and the inclusion of palliative cases. Similarly, perineural invasion, radiation dose and field size, and HER‐2/neu positivity did not prove to be important factors in our experience.

First Analysis of Patient Demographics, Technical Reproducibility, Cosmesis, and Early Toxicity Results of the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial

Eighty‐seven institutions participated in a Registry Trial that was designed to collect data on the clinical use of the MammoSite™ breast brachytherapy catheter for delivering breast irradiation. Patient demographics, technical reproducibility, cosmesis, and early toxicity were evaluated.

The conservative management of Paget's disease of the breast with radiotherapy

The purpose of this study was to evaluate the feasibility of breast‐conserving therapy involving limited surgery and definitive radiotherapy as a treatment for Pagets disease, and to determine the disease free and overall survival associated with this approach.

Conservative surgery and radiation in the treatment of synchronous ipsilateral breast cancers

Background. Conservative surgery (CS) and radiation therapy (RT) as an alternative to mastectomy is controversial in patients with two or more lesions in the same breast. The authors reviewed their experience with CS and RT in the management of patients with synchronous ipsilateral breast cancer (SIBC).

Repeat breast-conserving surgery for in-breast local breast carcinoma recurrence: the potential role of partial breast irradiation.

Mastectomy is the current standard of care for in‐breast local recurrence of breast carcinoma. The objective of the current study was to critically review the rationale for and the theoretic and actual risks and benefits of repeat breast‐conserving surgery followed by partial breast irradiation (PBI) for in‐breast local recurrence of breast carcinoma. The main outcomes of interest were local control and survival after in‐breast local recurrence and side effects, complications, and cosmesis after reirradiation of the breast. The risk of local recurrence was not found to be eliminated with mastectomy; approximately 2–32% of patients treated with mastectomy develop a chest wall recurrence. The interpretation of local control rates in evaluating repeat breast‐conserving surgery studies is difficult because of the lack of information regarding preoperative diagnostic mammography to rule out concurrent multicentric disease and microscopic margin status after surgery. Rates of subsequent local recurrence in these studies appeared to be between 19–50%, similar to reported rates of in‐breast local recurrence in patients with a first diagnosis of breast carcinoma who were treated with conservative surgery without irradiation. Early follow‐up studies of breast reirradiation suggest that catheter‐based interstitial brachytherapy and standard external beam radiation therapy can be delivered to the breast more than once without significant side effects in most patients and with acceptable cosmesis in some patients. Mastectomy may not be necessary in all patients with an in‐breast local recurrence of breast carcinoma. Recent advances in conformal radiation delivery and single‐center published reports concerning repeat breast‐conserving therapy support well designed prospective trials to formally test this hypothesis. Cancer 2004.

Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women

Patients diagnosed with ductal carcinoma in situ (DCIS) at a young age appear to have a different natural history and biology, including a higher local relapse rate, than patients diagnosed later in life. The current study compared various pathologic and molecular features of DCIS arising in a cohort of young women with those of DCIS arising in a cohort of older women to identify potential biologic differences between these two populations of patients.

A comparison of five immunohistochemical biomarkers and HER-2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early-onset breast carcinoma.

The objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early‐onset breast carcinoma.

Molecular markers for prognosis after isolated postmastectomy chest wall recurrence

Local chest wall recurrence after mastectomy occurs in 10–20% of patients with operable breast carcinoma. The objective of the current study was to assess the prognostic value of molecular markers at the time of local recurrence and to compare these markers with clinical variables.

Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma of the head and neck

Porfiromycin (methyl mitomycin C) has been shown in laboratory studies to have increased preferential cytotoxicity to hypoxic cells and therefore may provide enhanced therapeutic efficacy over mitomycin C when used in combination with radiation therapy (RT). The purpose of the two clinical studies reported here is to evaluate the concomitant use of porfiromycin with RT in the management of squamous cell carcinoma of the head and neck. Between October 1989 and July 1992, 21 patients presenting with locally advanced stage III/IV squamous cell carcinoma of the head and neck were entered into a phase I toxicity trial evaluating porfiromycin as an adjunct to RT. Patients were eligible if they had biopsy documented squamous cell carcinoma of the head and neck with a low probability of cure by conventional means. Patients were treated with standard fractionated daily RT to a total median dose of 63 Gy, with porfiromycin administered on days 5 and 47 of the course of RT. Upon completion of this phase I trial, a phase III trial was initiated in November 1992 randomizing patients with squamous cell carcinoma of the head and neck to RT with mitomycin C vs. RT with porfiromycin. There is no radiation only arm in this current trial. To date, 75 patients have been entered on this trial and acute toxicity data are available on 67 patients (34 porfiromycin, 31 mitomycin C) who have completed their entire course of treatment. Median follow-up of the 21 patients enrolled in the phase I porfiromycin trial is 58.5 months. Of the 21 patients, 5 were treated at a dose of 50 mg/M2, 4 at 45 mg/M2, and the final 12 at 40 mg/M2, which appeared to result in acceptable acute hematological and nonhematological toxicities. As of December 1995, 14 of the 21 patients have died with disease and 7 remain alive and free of disease, resulting in a 5-year actuarial survival of 32%. Of the patients enrolled to date in the phase III randomized trial of mitomycin C vs. porfiromycin, there have been no statistically significant differences between the two arms with respect to white blood cell count (WBC), platelet, or hemoglobin nadirs. Acute nonhematological toxicities including mucositis, epidermitis, odynophagia, and nausea have also been comparable. Two patients in this current randomized trial died during treatment, apparently of nondrug-related causes. We conclude that the bioreductive alkylating agent porfiromycin has demonstrated an acceptable toxicity profile to date. Final analysis of the phase I trial, which revealed a 5-year no evidence of disease survival rate of 32% in patients with locally advanced disease and a low probability of cure, appears encouraging. We anticipate completion of the current ongoing trial comparing mitomycin C to porfiromycin in the next 2 years. Further investigations, including large-scale multiinstitutional trials employing bioreductive alkylating agents or other hypoxic cell cytotoxins as adjuncts to RT, are warranted.

Prognostic Significance of Cyclin D1 Protein Levels in Early-Stage Larynx Cancer Treated With Primary Radiation

Recent laboratory experiments have demonstrated that cyclin D1 levels (cycD1) can influence radiosensitivity. The purpose of the current study is to evaluate the prognostic significance of cycD1 for local recurrence in early‐stage larynx cancer treated with primary radiation therapy. The study was conducted using a matched case‐control design in 60 early‐stage (T1‐T2/N0) larynx cancer patients. All patients had squamous cell carcinoma of the larynx and were treated with primary radiation to a total median dose of 66 Gy in daily fractions of 2 Gy, without surgery or chemotherapy. Thirty patients who suffered a local relapse in the larynx after treatment served as the index case population. These 30 cases were matched by age, sex, site (glottic vs. supraglottic), radiation therapy technique/dose, and follow‐up, to 30 control patients who did not experience a local relapse. Immunohistochemical staining from cycD1 was performed on the paraffin‐embedded specimens. The pathologist, blinded to the clinical information, scored each of the specimens on a four‐point intensity scale (0 = no stain, 1 = faint, 2 = moderate, 3 = strong) and percent distribution. Patients were considered to be positive for cyclin D1 if the staining was 2+ or greater with a percent distribution of at least 5%. By design of the study, the two groups were evenly balanced with respect to age, sex, stage, radiation dose, and follow‐up. CycD1 levels correlated with proliferating cell nuclear antigen levels. Low levels of cycD1 significantly correlated with local relapse; 19/30 (63%) of the index cases stained negative, while only 10/30 (33%) of the control cases stained negative (P = 0.03). These data suggest that low levels of cycD1 correlate with relatively radioresistant early‐stage larynx carcinoma. With larger more confirmatory clinical and laboratory data, this data may have significant clinical implications. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 22–28 (2000).