Gordon W. Philpott

Factors influencing cosmetic results after conservation therapy for breast cancer

PURPOSE Host, tumor, and treatment-related factors influencing cosmetic outcome are analyzed for patients receiving breast conservation treatment. METHODS AND MATERIALS Four-hundred and fifty-eight patients with evaluable records for cosmesis evaluation, a subset of 701 patients treated for invasive breast cancer with conservation technique between 1969 and 1990, were prospectively analyzed. In 243 patients, cosmetic evaluation was not adequately recorded. Cosmesis evaluation was carried out from 3.7 months to 22.3 years, median of 4.4 years. By pathologic stage, tumors were 62% T1N0, 14% T1N1, 15%, T2N0, and 9% T2N1. The majority of patients were treated with 4-6 MV photons. Cosmetic evaluation was rated by both patient and physician every 4-6 months. A logistic regression analysis was completed using a stepwise logistic regression. P-values of 0.05 or less were considered significant. Excellent cosmetic scores were used in all statistical analyses unless otherwise specified. RESULTS At most recent follow-up, 87% of patients and 81% of physicians scored their cosmetic outcome as excellent or good. Eighty-two percent of physician and patient evaluations agreed with excellent-good vs. fair-poor rating categories. Analysis demonstrated a lower proportion of excellent cosmetic scores when related to patient age > 60 years (p = 0.001), postmenopausal status (p = 0.02), black race (p = 0.0034), and T2 tumor size (p = 0.05). Surgical factors of importance were: volume of resection > 100 cm3 (p = 0.0001), scar orientation compliance with the National Surgical Adjuvant Breast Project (NSABP) guidelines (p = 0.0034), and > 20 cm2 skin resected (p = 0.0452). Extent of axillary surgery did not significantly affect breast cosmesis. Radiation factors affecting cosmesis included treatment volume (tangential breast fields only vs. three or more fields) (p = 0.034), whole breast dose in excess of 50 Gy (p = 0.0243), and total dose to tumor site > 65 Gy (p = 0.06), as well as optimum dose distribution with compensating filters (p = 0.002). Daily fraction size of 1.8 Gy vs. 2.0 Gy, boost vs. no boost, type of boost (brachytherapy vs. electrons), total radiation dose, and use of bolus were not significant factors. Use of concomitant chemotherapy with irradiation impaired excellent cosmetic outcome (p = 0.02). Use of sequential chemotherapy or adjuvant tamoxifen did not appear to diminish excellent cosmetic outcomes (p = 0.31). Logistic regression for excellent cosmetic outcome analysis was completed for age, tumor size, menopausal status, race, type of surgery, volume of breast tissue resected, scar orientations, whole breast radiation dose, total radiation dose, number of radiation fields treated, and use of adjuvant chemotherapy. Significant independent factors for excellent cosmetic outcome were: volume of tissue resected (p = 0.0001), type of surgery (p = 0.0001), breast radiation dose (p = 0.005), race (p = 0.002), and age (p = 0.007). CONCLUSIONS Satisfactory cosmesis was recorded in 81% of patients. Impaired cosmetic results are more likely with improper orientation of tylectomy and axillary incisions, larger volume of breast resection, radiation dose to the entire breast in excess of 50.0 Gy, and concurrent administration of chemotherapy. Careful selection of treatment procedures for specific patients/tumors and refinement in surgical/irradiation techniques will enhance the cosmetic results in breast conservation therapy.

Detection of recurrent and metastatic colorectal cancer: Comparison of positron emission tomography and computed tomography

AbstractBackground: This study evaluates the clinical value of positron emission tomography (PET) with 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) as compared to computed tomography (CT) in patients with suspected recurrent or metastatic colorectal cancer (CRC). Methods: A retrospective review of the records of 58 patients who had FDG-PET for evaluation of recurrent or advanced primary CRC was performed. FDG-PET results were compared with those of CT and correlated with operative and histopathologic findings, or with clinical course and autopsy reports. Results: Recurrent or advanced primary CRC was diagnosed in 40 and 11 patients, respectively. The sensitivity and specificity of FDG-PET were 91% and 100% for detecting local pelvic recurrence, and 95% and 100% for hepatic metastases. These values were superior to CT, which had sensitivity and specificity of 52% and 80% for detecting pelvic recurrence, and 74% and 85% for hepatic metastases. FDG-PET correctly identified pelvic recurrence in 19 of 21 patients; CT was negative in 6 of these patients and equivocal in 4. FDG-PET was superior to CT in detecting multiple hepatic lesions and influenced clinical management in 10 of 23 (43%) patients. Conclusion: FDG-PET is more sensitive than CT in the clinical assessment of patients with recurrent or metastatic CRC, and provides an accurate means of selecting appropriate treatment for these patients.

Impact of pneumoperitoneum on trocar site implantation of colon cancer in hamster model

BACKGROUND: Numerous anecdotal reports have documented the spread of colon cancer to trocar sites after laparoscopic-assisted colectomy. We hypothesized that the pneumoperitoneum of laparoscopy potentiated tumor adherence to trocar sites. PURPOSE: This study was designed to determine the affect of CO2pneumoperitoneum on the rate of tumor implantation at trocar sites. METHODS: Viable GW-39 human colon cancer cells were injected into the abdominal cavity of hamsters (2 × 106cells/hamster). A midline laparotomy, insertion of four 5-mm trocars, injection of viable cells into the mesentery of the cecum, and free peritoneal cavity was performed in two groups: one control group (41) who did not receive a pneumoperitoneum and a comparison group (50) who underwent pneumoperitoneum for ten minutes at an insufflation pressure of 10 mmHg. Animals were killed at six weeks, and hematoxylin and eosin-stained sections of trocar wounds, midline wound, small intestine, cecum, liver, and lung were examined by a veterinary pathologist, who was blinded to operation. RESULTS: Pneumoperitoneum increased tumor implantation in the cecal mesentery and the midline incision (P<0.05) but did not effect recurrence in the liver, lung, or jejunum. Trocar site implantation tripled with the addition of pneumoperitoneum (26vs.75 percent) (P<0.0001). CONCLUSION: Pneumoperitoneum increased implantation of free intra-abdominal cancer cells at wound sites on the abdominal wall or within the abdominal cavity in this animal model. The use of pneumoperitoneum during laparoscopy in patients with colon cancer should only be performed in a protocol setting to evaluate the effect of pneumoperitoneum on the treatment of cancer.

The treatment of malignant pleural effusions.

One hundred thirty‐three patients with 154 treated malignant pleural effusions were reviewed. Carcinoma of the breast, bronchogenic carcinoma, and lymphomas were the most frequent tumors causing malignant pleural effusion. Cytologies were positive in 67% of the 125 effusions examined. Local treatment consisted of thoracentesis, tube thoracostomy with or without nitrogen mustard instillation, irradiation, or pleurectomy. Patients were followed for recurrence of effusion and return of symptoms for an average of 6 1/2 months. Statistical analysis showed that 37% of 66 hemithoraces (60 patients) treated with tube thoracostomy and nitrogen mustard were free of effusion 3 months after treatment, and 29% 6 months after therapy. Fifty‐three percent of these patients were asymptomatic at 6 months, and 39% at 1 year after treatment. Thoracentesis with or without nitrogen mustard instillation was distinctly inferior to the tube and nitrogen mustard method. Pleurectomy in selected cases proved worthwhile.

Regional nodal management and patterns of failure following conservative surgery and radiation therapy for stage I and II breast cancer.

PURPOSE To determine the incidence, pattern of regional nodal failure, and treatment sequelae as determined by the extent of lymphatic irradiation. METHODS AND MATERIALS The records of 511 patients with 519 Stage I and II breast cancers treated with breast conserving surgery with or without axillary dissection and irradiation were reviewed. The extent of nodal irradiation was at the discretion of the attending radiation oncologist and varied considerably over the years. Management of the axilla consisted of axillary dissection alone in 351, axillary dissection and supplemental irradiation in 74, irradiation alone in 75, and simply observation in 21 patients. RESULTS Overall, axillary recurrence was uncommon (1.2%), but was slightly more frequent after irradiation alone (2.7%) than after surgery alone (0.3%), p = 0.14. There was no benefit for supplemental axillary irradiation after an axillary dissection yielding negative or 1 to 3 positive nodes. In the 21 patients in whom the axilla was observed, axillary recurrence was not observed. Supraclavicular failures were rare in women with negative or 1 to 3 positive axillary lymph nodes (0.5%), and not significantly affected by elective irradiation. Internal mammary node recurrence was seen in only one patient, and was not significantly influenced by elective internal mammary irradiation. Both arm and breast edema were significantly more common in women having breast and nodal irradiation than after breast irradiation alone. These sequelae were not influenced significantly by the number of lymph nodes obtained in the axillary dissection specimen. Radiation pneumonitis was seen with increased frequency with more extensive nodal radiotherapy. Pneumonitis was not found to be affected by the administration or sequencing of chemotherapy. CONCLUSION There is little justification for axillary or supraclavicular irradiation following an axillary dissection which yields negative or minimally involved (1 to 3 positive) lymph nodes. There were too few patients with extensive axillary node metastases (> or = 4 positive) in our series to draw conclusions about the optimal extent of nodal irradiation in this subset. Elective internal mammary lymph node irradiation increases technical complexity, does not appear to be advantageous, and when combined with supraclavicular irradiation places the patient at highest risk for pneumonitis.

The relationship between concentration of prostaglandin E and rates of cell replication

Abstract Prostaglandin (PGE) production in vitro was measured by radioimmunoassay and correlated with rates of cell proliferation of HEp-2, L and HeLa cells. Mean basal rates of PGE production (ng/10 6 cells/day) were inversely related to growth rates. Addition of dibutyryl cAMP (1 mM) to the media resulted in significant increases in PGE and inhibition of cell replication. Addition of PGE 1 to the media slowed growth by about 40%. Indomethacin at 10 −8 M inhibited PGE synthesis and resulted in significant stimulation of cell growth in all cell lines. Addition of PGE 1 to Indomethacin-containing media restored growth rates to those observed in the absence of Indomethacin. These observations demonstrate an inverse relationship between cell proliferation and PGE production during control and altered growth cycles.

Underlying pathology in mammary Paget's disease.

AbstractBackground: Management of patients with mammary Pagets disease is controversial; recent recommendations range from primary radiotherapy to modified radical mastectomy. This review correlates associated breast findings with disease stage and outcome to help guide evaluation and treatment. Methods: Retrospective review of clinical, mammographic and pathologic data from 38 women with mammary Pagets disease treated between 1979 and 1995 was performed. Mastectomies were performed on all but two patients with the entire breast and lymph nodes evaluated for histopathologic evidence of carcinoma. Results: Underlying carcinoma (ductal carcinoma in situ and/or invasive ductal cancer) was found in most patients (92%) even when no palpable mass was evident (85%); this carcinoma is often multifocal (73%). Mammography fails to identify the underlying disease in many patients with no palpable mass and multifocal underlying disease (64%). Patients with Pagets disease and a palpable mass have a much greater incidence of invasive cancer, multifocal lesions, and positive lymph nodes, and have worse survival. Conclusions: Although some patients with Pagets disease might be well treated by breast conservation therapy, many patients have underlying multifocal carcinoma (including invasive cancer), which can be inapparent by examination and mammography. Selecting candidates with disease amenable to complete excision without mastectomy is problematic.

Breast conservation therapy for intraductal carcinoma of the breast

PURPOSE Between 1979 and 1987, 76 women with 77 ductal carcinomas in-situ of the breast were evaluated by The Radiation Oncology Center after breast conservation surgery. METHODS AND MATERIALS Seventy breasts (91%) had tylectomy and irradiation and seven breasts (9%) had tylectomy alone. Median follow-up was 4.0 years, with a range of 2-10 years. Fifty patients (65%) had occult lesions discovered by mammography with a median mammographic size of 0.9 cm. The twenty-six patients with presenting symptoms had a median clinical tumor size of 1.95 cm. All patients had local excision of the primary tumor. Of 15 patients who had axillary dissections, one had nodal metastasis. Seventy breasts were irradiated. Seven patients refused radiotherapy. RESULTS Overall 5-year actuarial survival was 99%; 5-year actuarial disease-free survival was 89%; the 5-year actuarial intramammary tumor control rate for irradiated patients was 93% vs. 57% for patients not irradiated (p < 0.001). Comedocarcinoma had a 5-year actuarial tumor control rate of 75%, 88% in the irradiated group as compared to 98% for all other histologic subtypes of ductal carcinoma in situ (p < 0.03). All six patients with local failure were successfully salvaged by further surgery. Multivariate analysis revealed significant factors in local control to be (a) radiotherapy, (b) comedocarcinoma histology, and (c) menopausal status. CONCLUSIONS Although the number of patients treated is small, and follow-up time is limited, these early results support the contention that the treatment of ductal carcinoma in situ by excision and irradiation is an acceptable alternative to mastectomy. We urge caution in treating patients with the comedocarcinoma subtype and counsel these patients to have more treatment than excision alone.

Magnetic resonance imaging using gadolinium labeled monoclonal antibody

Gadolinium was attached to antibodies and tested in vitro and in vivo for its effect on proton relaxation enhancement. Using the cyclic anhydride method, diethylenetriaminepentaacetic acid (DTPA) was attached to albumin, IgG and anti-CEA monoclonal antibody. Gadolinium (Gd) was then chelated to the protein complexes forming protein-DTPA-Gd complex. With this technique approximately 9 atoms of Gd could be attached to each albumin molecule, 4 to each IgG molecule and 1.5 to each monoclonal antibody molecule. The minimal in vitro concentration of Gd in the form of IgG-DTPA-Gd necessary to produce proton relaxation enhancement at 0.35 tesla was 10(-1) mM. An in vivo experiment using anticarcinoembryonic antigen (CEA) monoclonal antibody-DTPA-Gd in hamsters implanted with human colon carcinoma resulted in a tumor concentration of Gd of less than 10(-4) mM. No enhancement of the tumors was detected at that concentration. For monoclonal antibodies to function as selective MR contrast agents, substantial advances in technology must occur.

Combined chemotherapy, radiation, and surgery for epithelial cancer of the anal canal

Combined chemotherapy and radiation therapy have been reported to produce a high incidence of complete regression of epithelial cancer of the anal canal, resulting in prolonged disease‐free survival. This modality has been advocated as an alternative to abdominoperineal resection as a primary treatment for this disease. Our group treated 19 patients between 1979 and 1985. Treatment included two infusions of 5‐fluorouracil (1000 mg/m2/24 hours), one dose of mitomycin C (15 mg/m2), and simultaneous whole‐pelvis radiation (3000 rad). The complete response rate was 88%. Three patients had anal cancer incompletely controlled by that therapy. They underwent abdominoperineal resections and are alive without disease at 10, 39, and 43 months, respectively. Actuarial disease‐free survival at 40 months was 87.5 ± 8.8 (% ± standard error of the mean [SEM]). Complications included gastrointestinal, hematologic, and cutaneous toxicity. These results confirmed a high complete response rate to this therapy. Local treatment failures may occur, but these may be salvaged with abdominoperineal resection.