Gayle Rawlings - Academia.edu (original) (raw)

Papers by Gayle Rawlings

Research paper thumbnail of Fragmentation and Consensus: Communitarian and Casuist Bioethics

Journal of Medical Ethics, 1998

Research paper thumbnail of Complications of whole abdominal and pelvic radiotherapy following chemotherapy for advanced ovarian cancer

International Journal of Radiation Oncology*Biology*Physics, 1992

We examined the records of 105 patients with advanced ovarian cancer who had been treated with ci... more We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.

Research paper thumbnail of Analysis of complications in patients treated with abdominopelvic radiation therapy for ovarian carcinoma

International Journal of Radiation Oncology*Biology*Physics, 1992

Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radi... more Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radiation therapy. Acute complications included nausea and vomiting in 364 patients (61%) which were severe in 36, and diarrhea in 407 patients (68%), severe in 35. Leukopenia (less than 2.0 x 10(9) cells/liter) and thrombocytopenia (less than 100 x 10(9) cells/liter) occurred in 64 patients (11%) each. Treatment interruptions occurred in 136 patients (23%), and 62 patients (10%) did not complete treatment. In both situations the most common cause was myelosuppression. Late complications included chronic diarrhea in 85 patients (14%), transient hepatic enzyme elevation in 224 (44%), and symptomatic basal pneumonitis in 23 (4%). Serious late bowel complications were infrequent: 25 patients (4.2%) developed bowel obstruction and 16 required operation. Multivariate analysis was unable to determine any significant prognostic factors for bowel obstruction; however, the moving-strip technique of radiation therapy was associated with a significantly greater risk of developing chronic diarrhea, pneumonitis, and hepatic enzyme elevation than was the open beam technique. We conclude that abdomino-pelvic radiation therapy as used in these patients is associated with modest acute complications and a low risk of serious late toxicity.

Research paper thumbnail of Borderline epithelial ovarian tumors: A review of 81 cases with an assessment of the impact of treatment

International Journal of Radiation Oncology*Biology*Physics, 1992

Optimal management of borderline epithelial ovarian tumors remains controversial because of the l... more Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.

Research paper thumbnail of Proliferation measurements with flow cytometry TPOT in cancer of the uterine cervix : correlation between two laboratories and preliminary clinical results

International Journal of Radiation Oncology Biology Physics, Jul 30, 1995

w To assess the prognostic value of the pm-treatment potential doubling time (T& in carcinoma of ... more w To assess the prognostic value of the pm-treatment potential doubling time (T& in carcinoma of the uterine cervix. Methods: Forty-six patients were studied prospectively from March, 1991 to August, 1993. Pm-treatment evaluation included examination under anaesthesia and obtaining a biopsy specimen 410 hours following the intravenous administration of bromodeoxyuridlne (200 mg). Tp was obtained by deriving the labelling index (L.I.) and S phase synthesis time (T,) using flow cytometry. Six patients were excluded: 2 due to technical problems with the assay, 2 patients had a vaginal primary, and 2 patients did not receive radiation therapy. The remaining 40 patients (average age 54 years, range 32-78) were treated with radical radiation therapy. There were 36 squamous and 4 adenocarcinomas. FIG0 stages were: Ib and IIa, 11 patients, IIb, 15 patients, III and IV, 14 patients. The median external beam dose was 50 Gy (range 45-52.8 Gy) delivered in 25 fractions (range 2533). The median intracavitary dose was 40 Gy delivered with a single line source to a point 2 an lateral of the midline, with a mean dose rate of 71 cGy/hr. The mean and median overall treatment time was 47 days (range 34-73 days). To date, 6 patients have died of disease, and the average follow-up for alive patients is 11.9 months (range 3.3-32.7 months). Results: There were 24 tumors with diploid DNA content and 16 tumors were aneuploid. The median and mean Tpot for the 40 patients were 5.7 and 6.8 days, respectively (range, 2025.6; c.v., 75%). When assessed 3 months post-treatment, 35 patients achieved a complete response, 2 had residual disease and 3 had progressive disease. To date, 26 patients remained disease-free, while 8 patients had pelvic failure and 7 patients developed distant metastases as the first failure site (1 patient developed both at the same time). In univariate analysis, significant prognostic factors for pelvic failure were: stage (p=O.O2), tumor size (p=O.OOl), initial hemoglobin level (p=O.O04), and overall treatment time (p=O.O2). A short TF or high L.I. was weakly associated with pelvic failure, although not statistically significant (Tpt, p-0.10; L.I., p=O.12). Age, S-phase fraction, DNA ploidy, and T, were not associated with pelvic failure. None of the examined variables predicted for distant failure. Multivariate models and survival analysis were not performed because of the relatively small number of patients and short follow-up.. Conclusions: In this uniformly treated group of patients with cancer of the uterine cervix, traditional clinical prognostic factors remain the most important. Preliminary data suggests that flow cytometry-determined Tp, and labelling index may have significance in predicting pelvic failure, although a larger number of patients with longer follow-up is required to assess its true prognostic significance.

Research paper thumbnail of Isolation and characterization of the sheep erythrocyte receptor in man

The Journal of Immunology, Jul 1, 1975

Properties of the sheep erythrocyte receptor on human lymphocytes were examined from two differen... more Properties of the sheep erythrocyte receptor on human lymphocytes were examined from two different aspects: inhibition of E-rosette formation by antisera, and extraction of T and non-T cells with 3 M KCl. Antisera to several T cell populations produced significant inhibition of E-rosette formation by human peripheral blood lymphocytes, whereas anti-B cell, anti-beta2-microglobulin, anti-I, and anit-i were ineffective. Sera with activity to HL-A subgroups on the HPBL tested produced complete rosette inhibition, although nonspecific anti-HL-A produced no inhibition. T cell preparations extracted by a 3M KCl technique contained activity that could be bound to SRBC and produce inhibition of rosette formation by HPBL. This inhibitory component could be quickly eluted from the SRBC and retain its inhibitory activity. No inhibitory activity could be demonstrated in extracts of B cells and non-lymphoid cells. These results suggest that 1) T cell-specific and HL-A specific antisera inhibit E-rosette formation; 2) beta2-M is not involved in the SRBC receptor as an active component; and 3) the receptor may be isolated by 3 M KCl extraction, and partially purified by the use of SRBC as a specific immunoadsorbent, without loss of biologic activity.

Research paper thumbnail of Borderline epithelial ovarian tumors: A review of 81 cases with an assessment of the impact of treatment

International Journal of Radiation Oncology*Biology*Physics, 1992

Optimal management of borderline epithelial ovarian tumors remains controversial because of the l... more Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.

Research paper thumbnail of Analysis of complications in patients treated with abdominopelvic radiation therapy for ovarian carcinoma

International Journal of Radiation Oncology*Biology*Physics, 1992

Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radi... more Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radiation therapy. Acute complications included nausea and vomiting in 364 patients (61%) which were severe in 36, and diarrhea in 407 patients (68%), severe in 35. Leukopenia (less than 2.0 x 10(9) cells/liter) and thrombocytopenia (less than 100 x 10(9) cells/liter) occurred in 64 patients (11%) each. Treatment interruptions occurred in 136 patients (23%), and 62 patients (10%) did not complete treatment. In both situations the most common cause was myelosuppression. Late complications included chronic diarrhea in 85 patients (14%), transient hepatic enzyme elevation in 224 (44%), and symptomatic basal pneumonitis in 23 (4%). Serious late bowel complications were infrequent: 25 patients (4.2%) developed bowel obstruction and 16 required operation. Multivariate analysis was unable to determine any significant prognostic factors for bowel obstruction; however, the moving-strip technique of radiation therapy was associated with a significantly greater risk of developing chronic diarrhea, pneumonitis, and hepatic enzyme elevation than was the open beam technique. We conclude that abdomino-pelvic radiation therapy as used in these patients is associated with modest acute complications and a low risk of serious late toxicity.

Research paper thumbnail of Definitive radiation therapy (XRT) in the management of bladder cancer

International Journal of Radiation Oncology*Biology*Physics, 1984

Research paper thumbnail of Long-term results of concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after surgery

International Journal of Gynecological Cancer, 1993

Between 1981 and 1991, 41 patients with carcinoma of the cervix recurrent only in the pelvis, or ... more Between 1981 and 1991, 41 patients with carcinoma of the cervix recurrent only in the pelvis, or pelvis and para-aortic nodes after initial surgery, were treated with concurrent chemo-radiation (CT-RT). The total dose of radiation was tailored to the disease extent. Radiation was delivered to the pelvis and/or pelvis plus para-aortic nodes. Concurrent infusional 5-fluorouracil 1.5 g m-2 day-1 was delivered with bid radiation for one to three courses of 3 or 4 days. In addition, 10 patients received one or two courses of intravenous mitomycin C (Mit C) 6 mg m-2. Twenty-three of 40 evaluable (58%) had a complete response to CT-RT. Five have subsequently relapsed, two in pelvis alone, one in pelvis and distant sites and two with distant metastases only. Eighteen of 40 (45%) remain alive without disease from 3 to 113 months (median 57 months) after CT-RT. Sustained complete remissions and apparent cure have occured even in poor pronosis patients with pelvic side wall or common iliac nodal diease and those recurrent at short intervals from surgery. Using logistic regression the following varibles were examined for their prognostic significance for pelvic control and survival: Mit C, extent of pelvic diseases number of course of 5-FU, nodal status at original surgery and radiation dose. On multivariate analysis only the number of courses of 5-FU used was predictive of pelvic control and survival. Concurrent 5-FU and radiation is recommended as salvage therapy for patients wth recurrent locoregional cervical cancer.

Research paper thumbnail of Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery

Gynecologic Oncology, 1987

Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surg... more Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surgery, have been dismal even when disease was apparently confined to the pelvis. Further surgery or radiation therapy cured only some with central pelvic disease alone who had recurred at intervals longer than 6 months after primary therapy. To try to improve the results of salvage therapy, we used a combination of concurrent chemotherapy, 5-Fluorouracil with or without Mitomycin-C, and radiation therapy. Seventeen patients were treated. Recurrent disease was present in the pelvis or pelvis and paraaortic nodes after radical surgery for Stage IB carcinoma of the cervix. Eight of seventeen (47%) are alive, disease-free, 21 to 58 months after therapy. Seven of the eight had biopsy proven recurrence. Five of eight had recurred within 9 months of primary surgery and 7/8 had a component of pelvic side wall disease. Thus the survivors had unfavorable prognostic features. Nevertheless, the use of concurrent radiation and chemotherapy produced an exceptionally high proportion of sustained complete remissions and possible cures.

Research paper thumbnail of Outcome of patients with unfavorable optimally cytoreduced ovarian cancer treated with chemotherapy and whole abdominal radiation

Gynecologic Oncology, 1991

There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despit... more There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despite optimal cytoreduction of tumor and abdominopelvic radiation. This study examined whether the survival of these patients, who have tumor with unfavorable histopathological characteristics and/or small residual disease, could be improved by giving chemotherapy before radiation. Forty-four out of fifty-one eligible patients, seen between 1981 and 1985, with Stage II or III disease were entered into the study. Following six courses of cisplatin-based chemotherapy, 33 (75%) received abdominopelvic radiotherapy. Survival was compared to that of 48 eligible matched control patients, treated with radiation between 1978 and 1981. The median follow-up is 6.6 years. The median survival was extended from 2.4 to 5.7 years (P = 0.13), and 42.6% of patients receiving combined therapy were free of relapse at 5 years, compared to 21.6% (P = 0.03) in the historical control group, treated with abdominopelvic irradiation alone. Only 2 of 44 patients in the combined group required surgery for bowel obstruction, as did 1 of 48 in the control group. Tolerance and toxicity of the combined approach were acceptable. Although we cannot be certain that the entire benefit we observed was not attributable to the chemotherapy alone, there is evidence that the radiotherapy may have been additive. Chemotherapy followed by abdominopelvic radiotherapy seems a reasonable management policy in these patients.

Research paper thumbnail of Carcinoma of the Vagina—Experience at the Princess Margaret Hospital (1974-1989)

Gynecologic Oncology, 1995

The charts of 153 patients with vaginal carcinoma or carcinoma in situ seen at Princess Margaret ... more The charts of 153 patients with vaginal carcinoma or carcinoma in situ seen at Princess Margaret Hospital between 1974 and 1989 were analyzed with respect to treatment modality, radiation dose and technique, complications, and survival. One hundred and twenty-eight patients were treated with radiation therapy, of which 10 received radiation postoperatively and 26 concomitant chemotherapy. The overall 5-year actuarial cause-specific survival was 66%. The 5-year cause-specific survivals by stage were Stage 0 (C-I-S) 100%, Stages I/II 77%, and Stages III/IV 56%. Late complications from treatment were infrequent and in only 12 patients were such complications classified as severe. Univariate analysis indicated that size and stage of tumor, histological grade, patient age, and radiation dose > 7000 cGy were significant factors in predicting survival, although in a multivariate analysis only size and stage retained significance. Fifty-one patients had a prior gynecological malignancy arising 1-37 years previously, of which 34 had cervical cancers. Radiotherapy is an effective treatment for all stages of carcinoma of the vagina and doses of at least 7000 cGy are recommended to maximize tumor control.

Research paper thumbnail of Proliferation measurements with flow cytometry Tpot in cancer of the uterine cervix: Correlation between two laboratories and preliminary clinical results

International Journal of Radiation Oncology*Biology*Physics, 1995

Research paper thumbnail of Phylloides tumor of the breast: A report of 14 cases

The objective of this retrospective study is to determine the role of radiation therapy in the ma... more The objective of this retrospective study is to determine the role of radiation therapy in the management of benign phylloides tumors. Fourteen patients with a diagnosis of benign phylloides tumor (PT) and registered at the Princess Margaret Hospital are included in the study. Definitive surgery consisted of either lumpectomy in seven patients or mastectomy in the other seven patients. One patient died of her disease, and the remaining patients had no evidence of disease at last follow-up (median 38.4 months). Among these 13 patients, 4 had at least one recurrence and the recurrence rate was higher for the group who underwent lumpectomy (43% compared with 28%). One patient was treated by lumpectomy and adjuvant radiation therapy, and had no subsequent recurrence (follow-up time 35.5 months). The role for radiation therapy in the management of this disease remains unclear.

Research paper thumbnail of Proliferation measurements with flow cytometry TpoT in cancer of the uterine cervix: Preliminary results

International Journal of Radiation Oncology Biology Physics, 1994

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Research paper thumbnail of Prognostic factors in patients with cervix cancer treated by radiation therapy: results of a multiple regression analysis

Radiotherapy and Oncology, 1995

A retrospective analysis of 965 patients with invasive cervix cancer treated by radiation therapy... more A retrospective analysis of 965 patients with invasive cervix cancer treated by radiation therapy between 1976 and 1981 was performed in order to evaluate prognostic factors for disease-free survival (DFS) and pelvic control. FIGO stage was the most powerful prognostic factor followed by radiation dose and treatment duration (P values = 0.0001). If the analysis was limited to patients treated

Research paper thumbnail of A pilot study of concurrent radiation, mitomycin C and 5Fluorouracil in poor prognosis carcinoma of cervix

Gynecologic Oncology, 1984

Research paper thumbnail of Outcome in breast cancer managed without an initial axillary lymph node dissection

Radiotherapy and Oncology, 1998

Purpose: The role of an elective axillary lymph node dissection (AxLND) in the initial management... more Purpose: The role of an elective axillary lymph node dissection (AxLND) in the initial management of patients with early stage breast cancer has recently become controversial. The objective of this current study is to review the reasons as to why patients from a single institution were managed without an initial AxLND and their outcome in terms of survival and recurrence rates.

Research paper thumbnail of Phylloides tumor of the breast: A report of 14 cases

Journal of Surgical Oncology, 1994

The objective of this retrospective study is to determine the role of radiation therapy in the ma... more The objective of this retrospective study is to determine the role of radiation therapy in the management of benign phylloides tumors. Fourteen patients with a diagnosis of benign phylloides tumor (PT) and registered at the Princess Margaret Hospital are included in the study. Definitive surgery consisted of either lumpectomy in seven patients or mastectomy in the other seven patients. One patient died of her disease, and the remaining patients had no evidence of disease at last follow-up (median 38.4 months). Among these 13 patients, 4 had at least one recurrence and the recurrence rate was higher for the group who underwent lumpectomy (43% compared with 28%). One patient was treated by lumpectomy and adjuvant radiation therapy, and had no subsequent recurrence (follow-up time 35.5 months). The role for radiation therapy in the management of this disease remains unclear.

Research paper thumbnail of Fragmentation and Consensus: Communitarian and Casuist Bioethics

Journal of Medical Ethics, 1998

Research paper thumbnail of Complications of whole abdominal and pelvic radiotherapy following chemotherapy for advanced ovarian cancer

International Journal of Radiation Oncology*Biology*Physics, 1992

We examined the records of 105 patients with advanced ovarian cancer who had been treated with ci... more We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.

Research paper thumbnail of Analysis of complications in patients treated with abdominopelvic radiation therapy for ovarian carcinoma

International Journal of Radiation Oncology*Biology*Physics, 1992

Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radi... more Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radiation therapy. Acute complications included nausea and vomiting in 364 patients (61%) which were severe in 36, and diarrhea in 407 patients (68%), severe in 35. Leukopenia (less than 2.0 x 10(9) cells/liter) and thrombocytopenia (less than 100 x 10(9) cells/liter) occurred in 64 patients (11%) each. Treatment interruptions occurred in 136 patients (23%), and 62 patients (10%) did not complete treatment. In both situations the most common cause was myelosuppression. Late complications included chronic diarrhea in 85 patients (14%), transient hepatic enzyme elevation in 224 (44%), and symptomatic basal pneumonitis in 23 (4%). Serious late bowel complications were infrequent: 25 patients (4.2%) developed bowel obstruction and 16 required operation. Multivariate analysis was unable to determine any significant prognostic factors for bowel obstruction; however, the moving-strip technique of radiation therapy was associated with a significantly greater risk of developing chronic diarrhea, pneumonitis, and hepatic enzyme elevation than was the open beam technique. We conclude that abdomino-pelvic radiation therapy as used in these patients is associated with modest acute complications and a low risk of serious late toxicity.

Research paper thumbnail of Borderline epithelial ovarian tumors: A review of 81 cases with an assessment of the impact of treatment

International Journal of Radiation Oncology*Biology*Physics, 1992

Optimal management of borderline epithelial ovarian tumors remains controversial because of the l... more Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.

Research paper thumbnail of Proliferation measurements with flow cytometry TPOT in cancer of the uterine cervix : correlation between two laboratories and preliminary clinical results

International Journal of Radiation Oncology Biology Physics, Jul 30, 1995

w To assess the prognostic value of the pm-treatment potential doubling time (T& in carcinoma of ... more w To assess the prognostic value of the pm-treatment potential doubling time (T& in carcinoma of the uterine cervix. Methods: Forty-six patients were studied prospectively from March, 1991 to August, 1993. Pm-treatment evaluation included examination under anaesthesia and obtaining a biopsy specimen 410 hours following the intravenous administration of bromodeoxyuridlne (200 mg). Tp was obtained by deriving the labelling index (L.I.) and S phase synthesis time (T,) using flow cytometry. Six patients were excluded: 2 due to technical problems with the assay, 2 patients had a vaginal primary, and 2 patients did not receive radiation therapy. The remaining 40 patients (average age 54 years, range 32-78) were treated with radical radiation therapy. There were 36 squamous and 4 adenocarcinomas. FIG0 stages were: Ib and IIa, 11 patients, IIb, 15 patients, III and IV, 14 patients. The median external beam dose was 50 Gy (range 45-52.8 Gy) delivered in 25 fractions (range 2533). The median intracavitary dose was 40 Gy delivered with a single line source to a point 2 an lateral of the midline, with a mean dose rate of 71 cGy/hr. The mean and median overall treatment time was 47 days (range 34-73 days). To date, 6 patients have died of disease, and the average follow-up for alive patients is 11.9 months (range 3.3-32.7 months). Results: There were 24 tumors with diploid DNA content and 16 tumors were aneuploid. The median and mean Tpot for the 40 patients were 5.7 and 6.8 days, respectively (range, 2025.6; c.v., 75%). When assessed 3 months post-treatment, 35 patients achieved a complete response, 2 had residual disease and 3 had progressive disease. To date, 26 patients remained disease-free, while 8 patients had pelvic failure and 7 patients developed distant metastases as the first failure site (1 patient developed both at the same time). In univariate analysis, significant prognostic factors for pelvic failure were: stage (p=O.O2), tumor size (p=O.OOl), initial hemoglobin level (p=O.O04), and overall treatment time (p=O.O2). A short TF or high L.I. was weakly associated with pelvic failure, although not statistically significant (Tpt, p-0.10; L.I., p=O.12). Age, S-phase fraction, DNA ploidy, and T, were not associated with pelvic failure. None of the examined variables predicted for distant failure. Multivariate models and survival analysis were not performed because of the relatively small number of patients and short follow-up.. Conclusions: In this uniformly treated group of patients with cancer of the uterine cervix, traditional clinical prognostic factors remain the most important. Preliminary data suggests that flow cytometry-determined Tp, and labelling index may have significance in predicting pelvic failure, although a larger number of patients with longer follow-up is required to assess its true prognostic significance.

Research paper thumbnail of Isolation and characterization of the sheep erythrocyte receptor in man

The Journal of Immunology, Jul 1, 1975

Properties of the sheep erythrocyte receptor on human lymphocytes were examined from two differen... more Properties of the sheep erythrocyte receptor on human lymphocytes were examined from two different aspects: inhibition of E-rosette formation by antisera, and extraction of T and non-T cells with 3 M KCl. Antisera to several T cell populations produced significant inhibition of E-rosette formation by human peripheral blood lymphocytes, whereas anti-B cell, anti-beta2-microglobulin, anti-I, and anit-i were ineffective. Sera with activity to HL-A subgroups on the HPBL tested produced complete rosette inhibition, although nonspecific anti-HL-A produced no inhibition. T cell preparations extracted by a 3M KCl technique contained activity that could be bound to SRBC and produce inhibition of rosette formation by HPBL. This inhibitory component could be quickly eluted from the SRBC and retain its inhibitory activity. No inhibitory activity could be demonstrated in extracts of B cells and non-lymphoid cells. These results suggest that 1) T cell-specific and HL-A specific antisera inhibit E-rosette formation; 2) beta2-M is not involved in the SRBC receptor as an active component; and 3) the receptor may be isolated by 3 M KCl extraction, and partially purified by the use of SRBC as a specific immunoadsorbent, without loss of biologic activity.

Research paper thumbnail of Borderline epithelial ovarian tumors: A review of 81 cases with an assessment of the impact of treatment

International Journal of Radiation Oncology*Biology*Physics, 1992

Optimal management of borderline epithelial ovarian tumors remains controversial because of the l... more Optimal management of borderline epithelial ovarian tumors remains controversial because of the lack of clear, universally accepted pathologic criteria for diagnosis, the lack of complete understanding of the significance of intraperitoneal implants, and the desire to employ more limited surgery in young women. We reviewed the experience with borderline epithelial ovarian tumors at Princess Margaret Hospital in order to assess the natural history of the disease, to determine prognostic factors that would aid in management decisions, and to determine if adjuvant therapy influenced outcome. Eighty-one patients were analyzed. The mean age was 48 years. Seventy-two percent of tumors were of the serous histologic sub-type and 28% were mucinous. Seventy-eight percent were Stage I, 11% Stage II, and 11% Stage III. Peritoneal washings contained malignant cells in 14 of 32 patients (not recorded or obtained in 49), cyst rupture occurred in 25%, surface excrescences in 40%, and adhesions in 46%. None of these factors had a significant effect on recurrence rate or survival. Eleven patients received adjuvant radiation therapy (10 abdomino-pelvic and 1 pelvic alone), four adjuvant chemotherapy, and one both radiation therapy and chemotherapy. The rest (65) received no adjuvant therapy. Due to the small numbers and infrequent events, it was not possible to analyze and thus draw valid conclusions regarding the effect of adjuvant therapy on survival or recurrence. The overall survival (OS) and cause specific survival (CSS) were 85% and 96% at 10 years, respectively. No Stage I patient died of tumor. OS for Stage I patients was 90% at 10 years, the majority of whom (61 of 63) received no adjuvant therapy, and is thus unnecessary in Stage I disease. The adequacy of unilateral oophorectomy or ovarian cystectomy could not be confirmed because of small numbers. The 10 year OS and disease-free survival in Stage II and III were 75% and 50%, respectively, despite the use of adjuvant radiation therapy, chemotherapy, or both. It is necessary to create a multi-center tumor registry in order to acquire a prospective data base from which to develop sound therapeutic decisions.

Research paper thumbnail of Analysis of complications in patients treated with abdominopelvic radiation therapy for ovarian carcinoma

International Journal of Radiation Oncology*Biology*Physics, 1992

Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radi... more Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radiation therapy. Acute complications included nausea and vomiting in 364 patients (61%) which were severe in 36, and diarrhea in 407 patients (68%), severe in 35. Leukopenia (less than 2.0 x 10(9) cells/liter) and thrombocytopenia (less than 100 x 10(9) cells/liter) occurred in 64 patients (11%) each. Treatment interruptions occurred in 136 patients (23%), and 62 patients (10%) did not complete treatment. In both situations the most common cause was myelosuppression. Late complications included chronic diarrhea in 85 patients (14%), transient hepatic enzyme elevation in 224 (44%), and symptomatic basal pneumonitis in 23 (4%). Serious late bowel complications were infrequent: 25 patients (4.2%) developed bowel obstruction and 16 required operation. Multivariate analysis was unable to determine any significant prognostic factors for bowel obstruction; however, the moving-strip technique of radiation therapy was associated with a significantly greater risk of developing chronic diarrhea, pneumonitis, and hepatic enzyme elevation than was the open beam technique. We conclude that abdomino-pelvic radiation therapy as used in these patients is associated with modest acute complications and a low risk of serious late toxicity.

Research paper thumbnail of Definitive radiation therapy (XRT) in the management of bladder cancer

International Journal of Radiation Oncology*Biology*Physics, 1984

Research paper thumbnail of Long-term results of concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after surgery

International Journal of Gynecological Cancer, 1993

Between 1981 and 1991, 41 patients with carcinoma of the cervix recurrent only in the pelvis, or ... more Between 1981 and 1991, 41 patients with carcinoma of the cervix recurrent only in the pelvis, or pelvis and para-aortic nodes after initial surgery, were treated with concurrent chemo-radiation (CT-RT). The total dose of radiation was tailored to the disease extent. Radiation was delivered to the pelvis and/or pelvis plus para-aortic nodes. Concurrent infusional 5-fluorouracil 1.5 g m-2 day-1 was delivered with bid radiation for one to three courses of 3 or 4 days. In addition, 10 patients received one or two courses of intravenous mitomycin C (Mit C) 6 mg m-2. Twenty-three of 40 evaluable (58%) had a complete response to CT-RT. Five have subsequently relapsed, two in pelvis alone, one in pelvis and distant sites and two with distant metastases only. Eighteen of 40 (45%) remain alive without disease from 3 to 113 months (median 57 months) after CT-RT. Sustained complete remissions and apparent cure have occured even in poor pronosis patients with pelvic side wall or common iliac nodal diease and those recurrent at short intervals from surgery. Using logistic regression the following varibles were examined for their prognostic significance for pelvic control and survival: Mit C, extent of pelvic diseases number of course of 5-FU, nodal status at original surgery and radiation dose. On multivariate analysis only the number of courses of 5-FU used was predictive of pelvic control and survival. Concurrent 5-FU and radiation is recommended as salvage therapy for patients wth recurrent locoregional cervical cancer.

Research paper thumbnail of Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery

Gynecologic Oncology, 1987

Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surg... more Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surgery, have been dismal even when disease was apparently confined to the pelvis. Further surgery or radiation therapy cured only some with central pelvic disease alone who had recurred at intervals longer than 6 months after primary therapy. To try to improve the results of salvage therapy, we used a combination of concurrent chemotherapy, 5-Fluorouracil with or without Mitomycin-C, and radiation therapy. Seventeen patients were treated. Recurrent disease was present in the pelvis or pelvis and paraaortic nodes after radical surgery for Stage IB carcinoma of the cervix. Eight of seventeen (47%) are alive, disease-free, 21 to 58 months after therapy. Seven of the eight had biopsy proven recurrence. Five of eight had recurred within 9 months of primary surgery and 7/8 had a component of pelvic side wall disease. Thus the survivors had unfavorable prognostic features. Nevertheless, the use of concurrent radiation and chemotherapy produced an exceptionally high proportion of sustained complete remissions and possible cures.

Research paper thumbnail of Outcome of patients with unfavorable optimally cytoreduced ovarian cancer treated with chemotherapy and whole abdominal radiation

Gynecologic Oncology, 1991

There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despit... more There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despite optimal cytoreduction of tumor and abdominopelvic radiation. This study examined whether the survival of these patients, who have tumor with unfavorable histopathological characteristics and/or small residual disease, could be improved by giving chemotherapy before radiation. Forty-four out of fifty-one eligible patients, seen between 1981 and 1985, with Stage II or III disease were entered into the study. Following six courses of cisplatin-based chemotherapy, 33 (75%) received abdominopelvic radiotherapy. Survival was compared to that of 48 eligible matched control patients, treated with radiation between 1978 and 1981. The median follow-up is 6.6 years. The median survival was extended from 2.4 to 5.7 years (P = 0.13), and 42.6% of patients receiving combined therapy were free of relapse at 5 years, compared to 21.6% (P = 0.03) in the historical control group, treated with abdominopelvic irradiation alone. Only 2 of 44 patients in the combined group required surgery for bowel obstruction, as did 1 of 48 in the control group. Tolerance and toxicity of the combined approach were acceptable. Although we cannot be certain that the entire benefit we observed was not attributable to the chemotherapy alone, there is evidence that the radiotherapy may have been additive. Chemotherapy followed by abdominopelvic radiotherapy seems a reasonable management policy in these patients.

Research paper thumbnail of Carcinoma of the Vagina—Experience at the Princess Margaret Hospital (1974-1989)

Gynecologic Oncology, 1995

The charts of 153 patients with vaginal carcinoma or carcinoma in situ seen at Princess Margaret ... more The charts of 153 patients with vaginal carcinoma or carcinoma in situ seen at Princess Margaret Hospital between 1974 and 1989 were analyzed with respect to treatment modality, radiation dose and technique, complications, and survival. One hundred and twenty-eight patients were treated with radiation therapy, of which 10 received radiation postoperatively and 26 concomitant chemotherapy. The overall 5-year actuarial cause-specific survival was 66%. The 5-year cause-specific survivals by stage were Stage 0 (C-I-S) 100%, Stages I/II 77%, and Stages III/IV 56%. Late complications from treatment were infrequent and in only 12 patients were such complications classified as severe. Univariate analysis indicated that size and stage of tumor, histological grade, patient age, and radiation dose > 7000 cGy were significant factors in predicting survival, although in a multivariate analysis only size and stage retained significance. Fifty-one patients had a prior gynecological malignancy arising 1-37 years previously, of which 34 had cervical cancers. Radiotherapy is an effective treatment for all stages of carcinoma of the vagina and doses of at least 7000 cGy are recommended to maximize tumor control.

Research paper thumbnail of Proliferation measurements with flow cytometry Tpot in cancer of the uterine cervix: Correlation between two laboratories and preliminary clinical results

International Journal of Radiation Oncology*Biology*Physics, 1995

Research paper thumbnail of Phylloides tumor of the breast: A report of 14 cases

The objective of this retrospective study is to determine the role of radiation therapy in the ma... more The objective of this retrospective study is to determine the role of radiation therapy in the management of benign phylloides tumors. Fourteen patients with a diagnosis of benign phylloides tumor (PT) and registered at the Princess Margaret Hospital are included in the study. Definitive surgery consisted of either lumpectomy in seven patients or mastectomy in the other seven patients. One patient died of her disease, and the remaining patients had no evidence of disease at last follow-up (median 38.4 months). Among these 13 patients, 4 had at least one recurrence and the recurrence rate was higher for the group who underwent lumpectomy (43% compared with 28%). One patient was treated by lumpectomy and adjuvant radiation therapy, and had no subsequent recurrence (follow-up time 35.5 months). The role for radiation therapy in the management of this disease remains unclear.

Research paper thumbnail of Proliferation measurements with flow cytometry TpoT in cancer of the uterine cervix: Preliminary results

International Journal of Radiation Oncology Biology Physics, 1994

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Research paper thumbnail of Prognostic factors in patients with cervix cancer treated by radiation therapy: results of a multiple regression analysis

Radiotherapy and Oncology, 1995

A retrospective analysis of 965 patients with invasive cervix cancer treated by radiation therapy... more A retrospective analysis of 965 patients with invasive cervix cancer treated by radiation therapy between 1976 and 1981 was performed in order to evaluate prognostic factors for disease-free survival (DFS) and pelvic control. FIGO stage was the most powerful prognostic factor followed by radiation dose and treatment duration (P values = 0.0001). If the analysis was limited to patients treated

Research paper thumbnail of A pilot study of concurrent radiation, mitomycin C and 5Fluorouracil in poor prognosis carcinoma of cervix

Gynecologic Oncology, 1984

Research paper thumbnail of Outcome in breast cancer managed without an initial axillary lymph node dissection

Radiotherapy and Oncology, 1998

Purpose: The role of an elective axillary lymph node dissection (AxLND) in the initial management... more Purpose: The role of an elective axillary lymph node dissection (AxLND) in the initial management of patients with early stage breast cancer has recently become controversial. The objective of this current study is to review the reasons as to why patients from a single institution were managed without an initial AxLND and their outcome in terms of survival and recurrence rates.

Research paper thumbnail of Phylloides tumor of the breast: A report of 14 cases

Journal of Surgical Oncology, 1994

The objective of this retrospective study is to determine the role of radiation therapy in the ma... more The objective of this retrospective study is to determine the role of radiation therapy in the management of benign phylloides tumors. Fourteen patients with a diagnosis of benign phylloides tumor (PT) and registered at the Princess Margaret Hospital are included in the study. Definitive surgery consisted of either lumpectomy in seven patients or mastectomy in the other seven patients. One patient died of her disease, and the remaining patients had no evidence of disease at last follow-up (median 38.4 months). Among these 13 patients, 4 had at least one recurrence and the recurrence rate was higher for the group who underwent lumpectomy (43% compared with 28%). One patient was treated by lumpectomy and adjuvant radiation therapy, and had no subsequent recurrence (follow-up time 35.5 months). The role for radiation therapy in the management of this disease remains unclear.