Diana B. Fischer

Yale-New Haven Hospital, New Haven, Connecticut, United States

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Publications (47)239.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Between 1970 and 1990, 1,008 patients with early-stage breast cancer were treated by conservative surgery without axillary dissection followed by radiation therapy to the intact breast in the Department of Therapeutic Radiology at Yale-New Haven Hospital. The patient population, broken down by histologic subtype, was as follows: 761 patients presented with infiltrating ductal carcinoma, 70 patients with pure intraductal, 38 intraductal with focal invasion, 54 infiltrating lobular, 21 tubular, 17 medullary, 16 mucinous, and 29 with other various histologic subtypes. Patients were followed on a regular basis by the referring physicians and radiation oncologists. Diagnostic studies for distant metastases were performed as clinically indicated. Annual mammography was a routine component of the follow-up program.As of 3/96, with a median follow-up of 10.5 years, 83 patients developed an ipsilateral breast tumor recurrence, and 109 patients developed distant metastases resulting in an overall 10-year breast recurrence-free rate of 84%, and a 10-year distant metastasis-free rate of 78%. There were significant differences in clinical stage, pathological nodal involvement, and administration of systemic therapy between various histologic subtypes. As expected, those patients with histologies of low metastatic potential (such as intraductal, tubular, and mucinous) had significantly superior distant recurrence-free survival rates. With respect to breast relapse rates, there were no statistically significant differences in the 5- and 10-year breast recurrence-free rates between any of the histologic subtypes. Patients with intraductal carcinoma with or without focal invasion had similar breast relapse rates as those with other histologic subtypes. Patients with lobular carcinoma in situ as a histologic component also had a similar overall breast relapse-free recurrence rate.In conclusion, long-term follow-up of conservatively treated breast cancer patients demonstrates no significant differences in ipsilateral breast tumor recurrence rates between various histologic subtypes. There are no histologies which had a statistically significantly higher breast-relapse rate than infiltrating ductal carcinomas and therefore no primary histologic subtype represents a relative contraindication to breast conservation therapy.
    The Breast Journal 01/2007; 3(1):7 - 14. DOI:10.1111/j.1524-4741.1997.tb00134.x · 1.43 Impact Factor
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    ABSTRACT: The purpose of this study is to investigate the implications of hypoxia and histological grade for survival in patients with gliomas. Tissue oxygen tension was measured intraoperatively using an Eppendorf pO2 Histograph. Survival was calculated from the date of the Eppendorf study to the date of last follow-up. Univariate analysis was performed stratifying patients by patient gender, type of anesthesia used, histological grade, extent of surgery, and patient age. Lastly univariate analysis was performed on the cohort after dichotomizing the median pO2 at 2.0 mmHg, 5.1 mmHg, and 10.0 mmHg. From March of 1996 to June of 1999, 25 patients were entered into this prospective trial. Two patients were excluded from analysis because polarographic measurements included normal brain tissue as well as tumor. Thus for analysis we included 13 patients with high grade gliomas (HGG) and 10 with low grade gliomas (LGG). The median tumor oxygen pressure for the entire cohort was 5.1 mmHg. Higher grade (P=0.0012) was prognostic for poorer survival. Patients were then stratified into groups with a median tumor oxygen tensions either above or below 2.0 mmHg, 5.1 mmHg, and 10.0 mmHg; there was no significant difference found in overall survival. Although histological grade was prognostic for survival, hypoxia, represented as the median tumor oxygen tension, was not a significant independent prognostic indicator of survival in this small and heterogeneous series of patients.
    The Cancer Journal 10/2006; 12(6):461-6. DOI:10.1097/00130404-200611000-00005 · 3.61 Impact Factor
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    ABSTRACT: Previous randomized trials have shown a benefit with concurrent use of the hypoxic cell cytotoxin mitomycin C (MC) and radiation (RT) in the management of squamous cell cancer of the head and neck (SCCHN). We conducted a randomized trial comparing MC with porfiromycin (POR) in combination with RT in the management of SCCHN. Between 1992 and 1999, 128 patients with SCCHN were enrolled in this prospective randomized trial. Patients were stratified by management intent, and balanced with respect to stage and site of disease. They were randomized to receive MC (15 mg/M(2)) or POR (40 mg/M(2)) on Days 5 and 47 (or last day) of RT. Of 121 evaluable patients, 61 were randomized to MC and 60 to POR. Patients were treated with standard daily RT to a total median dose of 64 Gy over 47 days. Patients were well balanced with respect to management intent, stage, site, age, sex, hemoglobin levels, tumor grade, radiation dose, and days on treatment. There were no significant differences between the two arms with respect to acute hematologic or nonhematologic toxicities. As of January 2003 with a median follow-up of 6.3 years, there have been 19 local relapses (4 MC vs. 15 POR), 21 regional relapses (7 MC vs. 14 POR), 24 distant metastases (11 MC vs. 13 POR), and 66 deaths (33 MC vs. 33 POR). MC was superior to POR with respect to 5-year local relapse-free survival (91.6% vs. 72.7%, p = 0.01), local-regional relapse-free survival (82% vs. 65.3%, p = 0.05), and disease-free survival (72.8% vs. 52.9%, p = 0.026). There were no significant differences between the two arms with respect to overall survival (49.2% vs. 54.4%) or distant metastasis-free rate (79.9% vs. 75.9%). Despite promising preclinical data, and an acceptable toxicity profile, POR was inferior to MC as an adjunct to RT in the management of SCCHN. This randomized trial emphasizes the need for randomized studies to evaluate new agents in the management of SCCHN.
    International Journal of Radiation OncologyBiologyPhysics 02/2005; 61(1):119-28. DOI:10.1016/j.ijrobp.2004.07.730 · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 09/2004; 60. DOI:10.1016/S0360-3016(04)01190-3 · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 10/2003; 57(2). DOI:10.1016/S0360-3016(03)01076-9 · 4.18 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the efficacy of mitomycin C as an adjunct to radiotherapy for the treatment of locally advanced cervix cancer. Patients with squamous-cell carcinoma of the cervix, stages IB2-IVA, were randomized to receive radiotherapy alone or radiotherapy with concomitant mitomycin C. An initial cohort of 160 patients, having a mean follow-up of 46 months, is analyzed. Intravenous mitomycin C, 15 mg/M(2), was given on the first and sixth week of radiotherapy. The 78 patients in the radiotherapy with mitomycin C group and 82 patients in the radiotherapy alone group have a comparable distribution by age and stage (mean age 47 years; stage IB 3%, IIA 11%, IIB 48%, IIIA 1%, IIIB 36%, IVA 3%). The four-year actuarial survival rates for radiotherapy with mitomycin C and radiotherapy alone were 72% and 56%, respectively (P = 0.13). The four-year actuarial disease-free survival rates for radiotherapy with mitomycin C and radiotherapy alone were 71% and 44%, respectively, a statistically significant difference (P = 0.01). The four-year actuarial local recurrence-free survival rates for patients receiving radiotherapy with mitomycin C and radiotherapy alone were 78% and 63%, respectively (P = 0.11). Differences in four-year distant recurrence-free survival between radiotherapy plus mitomycin C and radiotherapy alone were significantly different at 85% vs. 61% (P = 0.01); this analysis is not adjusted for local failure. On subgroup analysis, stage III-IVA patients had a four-year actuarial disease-free survival of 75% for radiotherapy plus mitomycin C compared with 35% for radiotherapy alone (P = 0.03). There were no treatment- related deaths. Mild hematologic toxicity was seen only in the group treated with mitomycin C. No excess in non-hematologic toxicity has been observed thus far with combined mitomycin C and radiotherapy. In this open phase III trial of mitomycin C as an adjunct to radical radiotherapy for squamous-cell carcinoma of the cervix, there were minimal hematologic effects and no increase in acute radiation reactions. A statistically significant difference in favor of patients receiving mitomycin C is shown for disease-free survival. Thus far, there are trends in favor of those patients receiving mitomycin C for survival and local control. Patients with more advanced stage disease, predominantly stage IIIB, appear to have the most benefit. These preliminary results support the hypothesis that targeting hypoxic cells may lead to a therapeutic enhancement in the radiotherapy of cervix cancer. This trial continues to accrue patients and follow-up data. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 206-223 (2000).
    International Journal of Cancer 09/2000; 90(4):206-23. DOI:10.1016/S0360-3016(99)90139-6 · 5.01 Impact Factor
  • E Obedian, D B Fischer, B G Haffty
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    ABSTRACT: To determine the risk of second malignancies after lumpectomy and radiation therapy (LRT), and to compare it with that in a similar cohort of early-stage breast cancer patients undergoing mastectomy without radiation (MAST). Between January 1970 and December 1990, 1,029 breast cancer patients at our institution underwent LRT. A cohort of 1,387 breast cancer patients who underwent surgical treatment by mastectomy (MAST), and who did not receive postoperative radiation during the same time period, served as a comparison group. Second malignancies were categorized as contralateral breast versus nonbreast. In the cohort of patients undergoing LRT, a detailed analysis was carried out with respect to age, disease stage, smoking history, radiation therapy technique, dose, the use of chemotherapy or hormone therapy, and other clinical and/or pathologic characteristics. As of March 1999, the median follow-up was 14.6 years for the LRT group and 16 years for the MAST group. The 15-year risk of any second malignancy was nearly identical for both cohorts (17.5% v 19%, respectively). The second breast malignancy rate at 15 years was 10% for both the MAST and LRT groups. The 15-year risk of a second nonbreast malignancy was 11% for the LRT and 10% for the MAST group. In the subset of patients 45 years of age or younger at the time of treatment, the second breast and nonbreast malignancy rates at 15 years were 10% and 5% for patients undergoing LRT versus 7% and 4% for patients undergoing mastectomy (P, not statistically significant). In the detailed analysis of LRT patients, second lung malignancies were associated with a history of tobacco use. There were fewer contralateral breast tumors in patients undergoing adjuvant hormone therapy, although this did not reach statistical significance. The adjuvant use of chemotherapy did not significantly affect the risk of second malignancies. There seems to be no increased risk of second malignancies in patients undergoing LRT using modern techniques, compared with MAST. Continued monitoring of these patient cohorts will be required in order to document that these findings are maintained with even longer follow-up periods. With nearly 15 years median follow-up periods, however, these data should be reassuring to women who are considering LRT as a treatment option.
    Journal of Clinical Oncology 07/2000; 18(12):2406-12. · 17.88 Impact Factor
  • E. Obedian, D. Fischer, B. Haffy
    International Journal of Radiation OncologyBiologyPhysics 01/1999; 45(3):194. DOI:10.1016/S0360-3016(99)90109-8 · 4.18 Impact Factor
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    ABSTRACT: 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. Radiat. Oncol. Invest. 5:235–245, 1997 © 1997 Wiley-Liss, Inc.
    Radiation Oncology Investigations 01/1997; 5(5):235 - 245. DOI:10.1002/(SICI)1520-6823(1997)5:5<235::AID-ROI4>3.0.CO;2-Z
  • International Journal of Radiation OncologyBiologyPhysics 01/1997; 39(2):227-227. DOI:10.1016/S0360-3016(97)80743-2 · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 01/1996; 36(1):219-219. DOI:10.1016/S0360-3016(97)85462-4 · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 01/1996; 36(1):331-331. DOI:10.1016/S0360-3016(97)85686-6 · 4.18 Impact Factor
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    ABSTRACT: To evaluate the efficacy of encapsulated ²⁴¹Am in the treatment of primary gynecological malignancies and in previously irradiated patients with recurrent disease in the pelvis. Encapsulated ²⁴¹Am primarily emits 60keV photons which are effectively shielded by thin layers of high atomic number materials. Dose distributions in water are similar to those produced by Cs-137 photons but with a half-value layer that is considerably less. Cases of 28 patients (12-primary, 16-recurrent) who have been treated with ²⁴¹Am at the Yale University School of Medicine since 1986 were retrospectively reviewed. Data concerning dosimetry, disease site, prior treatment, recurrence, disease-free survival, overall survival, and complications were evaluated.
    International Journal of Radiation OncologyBiologyPhysics 12/1995; 32:226-226. DOI:10.1016/0360-3016(95)97833-M · 4.18 Impact Factor
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    ABSTRACT: : DNA flow cytometry has been extensively studied in female breast carcinoma. However, there is limited data evaluating DNA ploidy in male breast cancer. In order to further assess the prognostic significance of DNA ploidy in male breast carcinoma, we retrospectively reviewed 55 cases (52 patients) of histologically proven male breast carcinoma treated at our institution from January 1971 through January 1992. Of the 55 cases, 32 paraffin-embedded blocks were available for DNA flow cytometry analysis. As of June 1993, median follow-up is 7.0 years. In the overall population of 55 cases, univariate analysis identified TNM stage, tumor size, and nodal status as significant prognostic indicators of overall survival and disease-free survival. In the 32 cases available for DNA flow cytometry, both local recurrences and distant metastases were more frequent in the aneuploid population. Univariate analysis revealed DNA ploidy to be a significant prognostic factor for local recurrence-free survival and distant metastasis-free survival. DNA ploidy correlated significantly with stage at diagnosis (p =.04), tumor size (p =.04) and nodal status (p =.02). In a multivariate analysis of 26 patients on whom all data were available (DNA ploidy, tumor size, clinical stage and nodal status), DNA ploidy was an independent predictor of disease-free survival (p =.05). In this retrospective analysis, we conclude that DNA ploidy has prognostic significance in male breast carcinoma.
    The Breast Journal 11/1995; 1(6):356-361. DOI:10.1111/j.1524-4741.1995.tb00262.x · 1.43 Impact Factor
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    ABSTRACT: It has been suggested that patients presenting with breast cancers within 2 cm of the nipple areolar complex represent a relative contraindication to conservative management due to either a compromised cosmetic result associated with sacrifice of the nipple areolar complex, reluctance to include the entire nipple areolar complex in the conedown field, or increased risk of multicentricity. We have reviewed our experience of conservatively treated patients with specific reference to the subset of patients presenting with tumors within 2 cm of the nipple areolar complex. Between January 1970 and December 1989, 1014 patients with early stage breast cancer were treated at Yale-New Haven Hospital by excisional biopsy with or without axillary lymph node dissection. Of the 1014 charts reviewed, a total of 98 patients fulfilled the criteria of having a central/ subareolar breast cancer. Reexcision was performed on only 16 patients. Following conservative surgery, patients were treated with radiation therapy to the intact breast to a total median dose of 48 Gy with conedown to a total of 64 Gy. adjuvant systemic therapy and regional nodal irradiation were administered as clinically indicated. As of December 1993, the median follow-up for the 98 patients in this study was 9.03 years. The majority of patients had presented with either a palpable mass or a mammographically detected lesion. Three patients presented with Paget's disease, five with nipple discharge, and seven with nipple inversion. Ten of the 98 patients had the nipple areolar complex sacrificed at the time of surgery, while the remaining 88 patients had the entire nipple areolar complex included in the conedown field. Four of these 88 patients had the nipple partially blocked during the electron conedown. There were no significant complications associated with including the entire nipple areolar complex within the conedown field to a median dose of 64 Gy. Six of the 98 patients experienced a local recurrence, three experienced a regional recurrence, and nine experienced distant metastasis. The actuarial 10-year survival (0.79 +/- 0.06), distant disease-free survival (0.88 +/- 0.04) and breast recurrence-free survival (0.84 +/- 0.07) were not significantly different from those patients who presented with cancers in other parts of the breast. Patients presenting with subareolar breast cancers within 2 cm of the nipple areolar complex are suitable candidates for conservative surgery and radiation therapy. In the majority of patients in this study, the nipple areolar complex did not need to be sacrificed and could be safely included in the electron conedown field with acceptable complications and cosmesis. A subareolar breast cancer does not represent a relative contraindication to conservative management in patients with early stage breast cancer.
    International Journal of Radiation OncologyBiologyPhysics 09/1995; 33(1):53-7. DOI:10.1016/0360-3016(94)90628-9 · 4.18 Impact Factor
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    ABSTRACT: Serum prostate specific antigen (PSA) values decrease after external beam radiation (EBRT) for clinically localized prostate cancer, reaching their nadir 6–12 months after treatment. The nadir PSA value is predictive of disease-free survival. This prospective study was initiated to evaluate whether the early response of PSA as measured by 1) the rate of PSA decrease during treatment (PSA slope) and 2) the immediate (within 1 month) post-treatment PSA would predict the PSA nadir.Thirty patients treated with EBRT for clinical stages A2-C2 (T1c-T3c) adenocarcinoma of the prostate were enrolled in this prospective study. Nine patients were subsequently excluded because they were lost to follow-up after less than 1 year (n = 6) or their pretreatment PSA was measured by a method other than Hybritech (n = 3). Serum PSA measurements were obtained at weeks 2, 4, and 6 of treatment (n = 21) as well as immediate post-treatment PSA at the first follow-up 2–4 weeks after treatment (n = 17). The end-point analyzed was whether or not the PSA nadir was ≦ 1.5 ng/ml. A linear regression model of log(PSA) vs. time (treatment week) was fit for each patient's data. The rate of decrease of PSA (PSA slope) was estimated from this regression. The PSA slope, pretreatment PSA, immediate post-treatment PSA, stage, and grade were studied by Cox life table regression analysis to determine predictors of PSA nadir. In the Cox model, time was measured from the start of radiotherapy until PSA ≦ 1.5 ng/ml or until the last measurement for those who did not reach this level. Models combining the significant individual factors were then constructed. The minimum follow-up is 52 weeks and the median is 66 weeks.The PSA slope (P = 0.05) and the immediate post-treatment PSA (P = 0.02) predicted a PSA nadir ≦ 1.5 ng/ml. Pretreatment PSA approached significance (P = 0.09). A model which combined pretreatment PSA and PSA slope predicted PSA nadir ≦ 1.5 ng/ml (P = 0.05) as did PSA slope combined with immediate post-treatment PSA (P = 0.01). Within each model, PSA slope was the stronger predictor.In conclusion, the early response of serum PSA as measured by the PSA slope and the immediate post-treatment PSA appears to be predictive of PSA nadir in patients treated with EBRT. More patients and longer follow-up are needed to confirm this finding and determine whether the early response predicts disease-free survival. © 1995 Wiley-Liss, Inc.
    Radiation Oncology Investigations 01/1995; 3(4):179 - 184. DOI:10.1002/roi.2970030406
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    ABSTRACT: Despite careful preoperative staging, approximately 50% of patients who undergo radical prostatectomy for clinical stage A2 (T1b-c) and B (T2) prostate cancer are found to have pathologic stage C (T3-4) or D (N1) disease. This study investigates whether preoperative serum prostate specific antigen (PSA) and Gleason grade predict pathologic stage among patients with clinically organ confined prostate cancer. The records of all 63 patients who underwent attempted pelvic lymphadenectomy and radical prostatectomy for adenocarcinoma of the prostate at our institution in 1990-91 were retrospectively reviewed. Patients with a preoperative serum PSA of 12.5 ng/mL or greater had an 81% incidence of pathologic upstaging to stage C (T3-4) or D (N1) compared with 38% for patients with a PSA less than 12.5 (p = 0.0015). The incidence of various pathologic findings for prostate specific antigen > or = 12.5 vs. prostate specific antigen < 12.5 was as follows: seminal vesicle involvement 29% vs. 5% (p = 0.0186), lymph node metastases 24% vs. 0% (p = 0.0029), capsular penetration 71% vs. 38% (p = 0.0424), and positive margins 47% vs. 36% (p = 0.56). None (0/3) of the patients with Gleason grade 4 or less were pathologically upstaged compared with 49% (24/49) of patients with grade 5-7 tumors (p = 0.15) and 82% (9/11) of patients with grade 8 or higher cancers (p = 0.0474, grade 5-7 vs. 8-10). Within the group of patients with Gleason grade 5-7, a prostate specific antigen of 12.5 ng/mL or greater predicted an 79% rate of upstaging compared with 37% for patients with prostate specific antigen less than 12.5 (p = 0.0098). Patients with clinical Stage A2 (T1b-c) or B (T2) prostate cancer who have Gleason grade 8-10 tumors and those patients with Gleason grade 5-7 tumors with a preoperative serum prostate specific antigen of 12.5 ng/mL or higher have a high incidence of pathologic upstaging. These patients should be preferentially treated with external beam radiation in most cases.
    International Journal of Radiation OncologyBiologyPhysics 10/1994; 30(2):317-22. DOI:10.1016/0360-3016(93)90885-Y · 4.18 Impact Factor
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    ABSTRACT: Background. The purpose of this study is to determine the impact of adjuvant systemic chemotherapy and adjuvant hormonal therapy on local relapse in the conservatively treated breast.Materials and Methods. Before December 1989, 548 patients underwent lumpectomy with axillary dissection followed by radiation therapy to the intact breast. Adjuvant systemic therapy was administered as clinically indicated. The majority of patients with pathologically involved lymph nodes received adjuvant systemic therapy, whereas those with pathologically negative lymph nodes received no adjuvant systemic therapy. The majority of patients received a course of radiation therapy either concomitant with or before systemic therapy. In only nine cases was radiation therapy delayed more than 16 weeks after surgery.Results. As of June 1992, the 548 patients had a median follow-up of 6.4 years. In univariate and multivariate Cox regression analysis, patient age and adjuvant systemic chemotherapy were statistically significant independent prognostic factors relating to breast relapse. Those patients who received adjuvant systemic chemotherapy had a lower breast relapse than those who did not. Among patients who received tamoxifen, there was a statistically insignificant trend toward a lower relapse rate compared with those who did not receive tamoxifen.Conclusions. It appears from this retrospective analysis that patients who received adjuvant systemic therapy, either concomitantly or after their course of radiation therapy, had a lower relapse rate in the conservatively treated breast than those patients who received no adjuvant systemic therapy.
    Cancer 05/1994; 73(10):2543 - 2548. DOI:10.1002/1097-0142(19940515)73:10<2543::AID-CNCR2820731015>3.0.CO;2-7 · 4.90 Impact Factor
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    ABSTRACT: The purpose of this study was to perform a detailed clinical pathological analysis of breast relapses in patients treated with conservative surgery and radiation therapy in an effort to classify those relapses as true local recurrences or second primary tumors, and to assess the prognostic and therapeutic implications of such a classification system. Of 990 patients treated with conservative surgery and radiation therapy at our facilities prior to December 1987, 82 patients have experienced a relapse in the conservatively treated breast as the primary site of failure. Patients were classified as having new primary tumors if they fulfilled any one of the following criteria: a) breast relapse occurring at a site distinctly removed from the original tumor; b) histology of the breast relapse compared with the original tumor consistent with a new primary; or c) DNA flow cytometry converting from an aneuploid primary to a diploid relapse. As of 2/92, with a median follow-up of 5.4 years from the time of breast relapse, the overall 5-year survival rate following breast relapse was 55%. Forty-seven patients were classified as true recurrences and 33 patients were classified as new primaries. Patients classified as true recurrences had a shorter median time to breast relapse than patients classified as new primaries (3.16 years vs. 5.42 years, p < .05) and an inferior post breast recurrence survival rate compared to patients classified as new primaries (36% vs. 89%, p < .05). Residual disease outside of the recurrent tumor bed was also noted to be more frequent in patients classified as true recurrences compared to patients classified as new primaries (48% vs. 16%, p < .05). Based on the clinical and pathological criteria outlined, it appears that a significant portion of patients experiencing a relapse in the conservatively treated breast may have new primary tumors as opposed to true local relapses. Distinction between a true recurrence and a new primary tumor may have significant prognostic implications. Uncertainties associated with the clinical and pathological criteria are presented and further investigations with genetic fingerprinting techniques to establish the clonality of breast relapses are presented and discussed.
    International Journal of Radiation OncologyBiologyPhysics 10/1993; 27(3):575-83. DOI:10.1016/0360-3016(93)90382-6 · 4.18 Impact Factor
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    ABSTRACT: Purpose: A phase I toxicity trial aimed at defining an appropriate dose of the bioreductive alkylating agent porfiromycin to be used in conjunction with radiation therapy in patients with squamous cell carcinoma of the head and neck. Methods and Materials: A total of 21 patients were entered into this phase I clinical trial. All patients had locally advanced squamous cell carcinoma of the head and neck and were treated with radiation therapy with or without surgical intervention. Porfiromycin was administered on days 5 and 47 of the course of radiation therapy. The initial dose of the drug was 50 mg/M2, but due to hematological toxicity the dose was lowered to 40 mg/M2. The final 12 of the 21 patients in this phase I clinical trial was treated at the dose of 40 mg/M2. Radiation therapy was directed at the primary site and regional lymph nodes as clinically indicated with conventional fractionations of 200 cGy/day to total doses in excess of 6,000 cGy. Results: Five patients were treated at the initial dose of 50 mg/M2, but due to excessive hematologic toxicity the dose was reduced to 45 mg/M2 for 4 patients and lowered again to 40 mg/M2 for the final 12 patients of the study. As expected, the major toxicity was hematological with thrombocytopenias and neutropenias. There were no clinically evident bleeding episodes secondary to thrombocytopenia and no neutropenic deaths during the course of the study. Of the 21 patients treated in the series, 10 remain alive no evidence of disease (NED) with a median follow-up of 18.5 months. Four of the alive NED patients have been followed for over 2 years. Conclusions: The bioreductive alkylating agent porfiromycin may be safely administered at a dose of 40 mg/M2 to patients undergoing radiation therapy for squamous cell carcinoma of the head and neck. Based on the results of this phase I trial, we have now mounted a phase III clinical trial in patients with all stages of squamous cell carcinoma of the head and neck, comparing radiation therapy with porfiromycin to radiation therapy with mitomycin C. There is no radiation therapy without drug in this phase III clinical report. © 1994 Wiley-Liss, Inc.
    Radiation Oncology Investigations 01/1993; 1(5):297 - 304. DOI:10.1002/roi.2970010508

Publication Stats

1k Citations
239.46 Total Impact Points

Institutions

  • 1976–2000
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
  • 1988–1993
    • Yale University
      • Department of Therapeutic Radiology
      New Haven, Connecticut, United States
  • 1978
    • Danbury Hospital
      Danbury, Connecticut, United States