GYNECOLOGIC ONCOLOGY 3, 251-257 (1975)
Gynecologic Oncology Group Reports I and II M. M. HRESHCHYSHYN,M.D. 1 Gynecologic Oncology Group, Buffalo, New York Received April 23, 1975 The Gynecologic Oncology Group is a multi-institutional group of interdisciplinary composition supported by the National Cancer Institute and involved in cooperative controlled studies of problems in gynecologic cancer.
I. GYNECOLOGIC ONCOLOGY GROUP The Gynecologic Oncology Group (GOG) was founded in New York on February 20, 1970, by oncologists interested in clinical research for the benefit of gynecologic cancer patients. The group has been supported by the National Cancer Institute since May 1, 1971. A precursor group studying corpus carcinoma adjuvant treatment had existed before. It soon became apparent, however, that there was a need for a group that would study the entire field of gynecologic oncology and would provide for a multidisciplinary input; that is, not just from gynecologists but also from those in the fields of radiotherapy, medical oncology, pathology, and others. This realization led to the formation of the GOG, which is a cooperative group of institutions, each represented by a gynecologist, medical oncologist, pathologist, and related specialists, one of whom serves as the Principal Investigator in the institution. The G O G conducts controlled clinical trials involving all accepted and experimental treatment methods in a large number of patients with all types of gynecologic cancer. It is also involved, to a limited extent, in laboratory research that fits into the multi-institutional framework of the group. It is hoped that through this cooperative effort answers can be obtained to outstanding questions in gynecologic oncology within a reasonable period of time, including those otherwise not readily obtainable from an single institution. The structure of the G O G consists of the Group Membership, an Operations Office, and committees (Fig. 1).
GIR~ ST~C~Z
N?[ ~ERATICt+SOFFICE
/
\
GROUP ~zI~ERSHIP
GOG COM~ITfEES
FIGURE 1 1 Protocol Chairman, G O G Group Chairman (1970-1975). 251 Copyright (~) 1975 by Academic Press, Inc. All rights of reproduction in any form reserved.
252
M. M. HRESHCHYSHYN
The Executive Committee, elected by the membership, is the policy-recommending body for the G O G , and the group membership, which meets twice a year, is the decision-making body. The Operations Office fulfills its administrative and statistical needs. Any institution with demonstrable potential to contribute to the studies of the group may apply for membership. At the present time, only institutions in the United States are eligible as members of the G O G for direct support by the National Cancer Institute. A new member remains in probationary, or provisionary, status for at least 1 year before becoming eligible for full (voting) membership, provided that its contribution to the group activities has been found satisfactory. A full-member institution, however, may be placed back in the probationary category and its membership may be discontinued for lack of satisfactory performance. Since its inception, the G O G membership has increased from 10 to 34, 2 which provides a pool of approximately 4000 new invasive gynecologic cancer patients a year available for G O G studies. The Operations Office consists of the Chairman's Office, a Statistical Office, Pathology and Radiotherapy Repositories, and a central Endocrine Laboratory (Fig. 2). The group chairman is elected by the membership for a 5-year period. He is responsible for the administration of the G O G . In addition, there is an executive officer who performs the function of vice-chairman. The group's biostatistician is in charge of the statistical unit. The Pathology and Radiotherapy Repositories collect and store in the Operations Office histologic and radiotherapy material on all study patients. The materials are reviewed periodically by the Pathology and Radiotherapy Committees
STATISTICALOFF]CE
~OLOGY F~POSITORY
I
FIG. 2. GOG operations office. 2 Member institutions include the following. Brown Affiliated Hospitals, Duke University Medical Center, Emory University Clinic, George Washington University Medical Center, Georgetown University & Affiliated Hospital, Hahnemann Medical College Hospitals, Henry Ford Hospital, Hospital of the University of Pennsylvania, Louisiana State University Medical School, Milton S. Hershey School of Medicine, Mount Sinai School of Medicine, New York Medical College, Northwestern School of Medicine, Roswell Park Memorial Institute, Rush-Presbyterian-St. Luke's Medical Center, State University of New York at Buffalo, University of Alabama Hospitals & Clinics, University of California at Los Angeles, University of California at San Diego, University of Cincinnati, University of Colorado Medical Center, University of Indiana, University of Iowa Hospitals & Clinics, University of Kansas Medical Center, University of Miami School of Medicine, University of Mississippi Medical Center, University of North Carolina, University of Rochester Medical Center, University of Southern California at Los Angeles, University of Texas Health Science Center at Dallas, University of Texas Medical Branch at Galveston, University of Utah Medical Center, Walter Reed Army Medical Center, and Wayne State University School of Medicine.
TABLE 1 GYNECOLOGIC ONCOLOGY GROUP'S CURRENT STUDY PROTOCOLS No.
Protocol
1 Postoperative treatment of women with resectable ovarian cancer with RT or melphalan or no further treatment 2 Postoperative treatment of women with Stage III ovarian cancer by RT or melphalan either alone or in both sequences 3 Treatment of women with disseminated or recurrent advanced ovarian cancer with melphalan alone; in combination with 5-FU; in combination with 5-FU and dactinomycin; or with the combinations of cytoxan, 5-FU, and dactinomycin 4 Treatment of women with cervical cancer Stages IIIb and IV confined to the pelvis with hydroxyurea or placebo both in combination with RT 5 Study of the relationship between growth pattern and lymphangetic and Vascular involvement in women with Stage Ia cervical cancer 6 The study of peritoneal fluid cellular patterns in women with Stage Ia and Ib adenocarcinoma of the ovary included in Protocol No. 1 of the Gynecologic Oncology Group 7 The study of peritoneal fluid cellular patterns in women with Stage III or IV ovarian carcinoma treated in Protocol Nos. 2 and 3 of the Gynecologic Oncology Group 10 Treatment of women with malignant embryonal carcinoma and malignant teratomas without neural elements with a combination of dactinomycin, VCR, and cyclophosphamide (Phase II) 11 Treatment of women with malignant teratomas containing neural elements with a combination of dactinomycin, VCR, and cyclophosphamide (Phase II) 12 Treatment of women with ovarian germ cell tumors containing choriocarcinoma with a combination of dactinomycin, MTX, and chlorambucil (Phase II) 13 Treatment of women with mixed mesodermal tumors of the ovary with a combination of dactinomycin and VCR given concomitantly with RT followed by a maintenance regimen with cyclophosphamide (Phase II) 14 Treatment of women with malignant tumors of the ovarian stroma, such as granulosa cell cancers, granulosa thecal cell cancers, and arrhenoblastomas, with either a combination of dactinomycin, 5-FU, and cyclophosphamide or with RT (Phase II-III) 16 A randomized comparison of preoperative and postoperative irradiation in the treatment of women with Stage I, Grades 2 and 3 adenocarcinoma of the endometrium 17 Treatment of advanced adenocarcinoma of the endometrium with radiotherapy and progestin 18 Treatment of women with adenocarcinoma (and adenoacanthoma) of the endometrium FIGO Stage II by surgery, RT, or combinations of both 19 Exploratory celiotomy for surgical staging of cervical cancer 20 Randomized study of prophylactic adriamycin versus no adjuvant chemotherapy in Stage I and II uterine sarcomas 21 Randomized study of adriamycin versus adriamycin plus dimethyl triazeno imidazole carboxamide in advanced uterine sarcomas 23 Comparison of the therapeutic effects of adriamycin vs. ADM + VCR vs ADM + cyclopfiospfiamide in the treatment of advanced carcinoma of the cervix (modified Phase II-III)
Study chairman (men)
Dr. M. Hreshchyshyn Dr. S. Kaplan
D r . S. Kaplan
Dr. M. Hreshchyshyn
Dr. S. Sail
D r . L . McGowan
Dr. L. McGowan Dr. R. Slayton and Dr. M. Hreshchyshyn Dr. R. Slayton and Dr. M. Hreshchyshyn Dr. M. Hreshchyshyn and Dr. R. Slayton
Dr. R. Slayton and Dr. L. Brady
Dr. R. Slayton and Dr. L. Brady Dr. C. P. Morrow and Dr. P. DiSaia Dr. C. P. Morrow and Dr. P. DiSaia Dr. C. Cohen and Dr. S. Sail Dr. H. Averette Dr. G. Omura Dr. G. Omura Dr. H. J. Wallace and Dr. M. Hreshchyshyn
254
M. M. H R E S H C H Y S H Y N
Tt~RC~IT[ZES ADMINISTPATIVECO~II~EkS
E)~CUTI~ tI?~EE g~BERSHIPCO~ITI~E Ir/-L~3 Ca'fIIT~E pgJTOCOLF£VIEWCO~IT~E gJALIIY CONTROLCOr~IITEE
FIGURE 3
~AIT~TCOFRITTESS CHEPIOIHEP#~PYCOMMIIII~S Iff~NOLORVCO~MIITEE PATHOLOGYCOffIITIEE PADIOI~HEI~PYCEt~IITIEE
FIGURE 4
CO~NITCE 011 INVASIVEND PRE-IINASIVEpIALIGNNCIES OF THE CERVIX,VULVA/~IDVAGINA HIID~ETRIALC~CER COff~IT~ OVARIAI~Ca~!CERCO~ITIF_E SARCC~A COM~IITIEE
FIGURE 5
and the Radiologic Physics Center. The Radiologic Physics Center is also responsible for monitoring radiation equipment of the participating institutions. The Central Endocrine Laboratory performs assays for gonadotropins and steroids. In addition to the Executive Committee, there are a number of committees appointed by the chairman of the group. These can be divided into (a) administrative, (b) treatment, and (c) tumor committees (Figs. 3, 4, 5). The names of the committees are indicative of their functions. In general, the administrative committees evaluate and monitor the bylaws, membership, institutional contributions to G O G activities, protocol design, and quality of data. The treatment committees monitor the interdisciplinary input into the G O G and the quality of various treatments in ongoing studies. Tumor committees concern themselves with the need for studies in particular cancer types and the evaluation of ongoing studies. Clearly, the work of the various committees is interrelated, and joint sessions for purposes of resolving specific problems are not uncommon. Since the G O G was established, it has instituted 23 protocols, 19 of which (Table 1) are presently active, of various gynecologic tumor types and stages of the disease. Eleven of these protocols deal with ovarian, 4 with cervical, 3 with corpus carcinoma, and 2 with uterine sarcomas. In all, 2003 patients were entered into these s t u d i e s - approximately 1000 of them during the last year, which shows the rapid acceleration in the G O G studies. Some of these studies are close to completion, and we will be reporting our preliminary results soon. II. Treatment of Women with Cervical Cancer Stages IIIb and IV Confined to the Pelvis with Hydroxyurea or Placebo Both in Combination with Radiation Therapy
Results of an earlier study conducted by this investigator on the use of hydroxyurea in combination with radiation in the treatment of patients with advanced cervical carcinoma suggested that the combination is superior to radiotherapy alone, particularly in control of Stage IIIb of the disease [1]. The Gynecologic Oncology Group undertook to test these findings. Patients with primary squamous carcinoma of the cervix, Stage IIIb and IVa, were eligible. The protocol design is shown in Fig. 1. Randomization is carried out via the closed-envelope technique. Response to treatment is evaluated in terms of toxicity, changes in tumor mass, duration of progression-free interval, and patient survival. Analysis of the data was prepared by Dr. John Blessing,
255
GYNECOLOGIC ONCOLOGY REPORTS I AND II
Randomize 80 mg./kg, every 3 days/12 weeks
FH+ydroxyurea
REGIMENI [+ExternalIrradiation 5000 rads to the pelvis/5-8 week~ ~tracavitary Radium 3000 rads to Point A
+~acebo
80 mg./kg, every 3 days/12 weeks
~REGIMEN II [+External Irradiation
5000 rads to the pelvis/5-8 weeks
L~tracavitary Radium 3000 fads to Point A
Fro. 1. GOG protocol # 4. Treatment of women with cervical cancer Stages IIIb and IV confined to the pelvis with hydroxyurea or placebo both in combination with radiation therapy.
TABLE 1 PATIENT ENT~ES
Treatment
No. entered
No. excluded
No. eligible
No. evaluable for toxicity
No. evaluable for survival
130 121 251
26 26 52
104 95 199
82 78 160
84 83 167
I
II Total
TABLE 2
REASON FOR EXCLUSION BY TREATMENT Treatment Reason for exclusion
I
II
Ineligible Protocol violation Refused treatment Removed by investigator Clerical error Other Total
5 6 11 2 1 1 26
16 4 5 0 1 0 26
TABLE 3 ToxICITY BY TREATMENT (SUMMARY) Chemotherapy
Radiotherapy
RX
No. evaluated
WBC < 3000 platelets
or
Gynecologic Oncology Group Reports I and II M. M. HRESHCHYSHYN,M.D. 1 Gynecologic Oncology Group, Buffalo, New York Received April 23, 1975 The Gynecologic Oncology Group is a multi-institutional group of interdisciplinary composition supported by the National Cancer Institute and involved in cooperative controlled studies of problems in gynecologic cancer.
I. GYNECOLOGIC ONCOLOGY GROUP The Gynecologic Oncology Group (GOG) was founded in New York on February 20, 1970, by oncologists interested in clinical research for the benefit of gynecologic cancer patients. The group has been supported by the National Cancer Institute since May 1, 1971. A precursor group studying corpus carcinoma adjuvant treatment had existed before. It soon became apparent, however, that there was a need for a group that would study the entire field of gynecologic oncology and would provide for a multidisciplinary input; that is, not just from gynecologists but also from those in the fields of radiotherapy, medical oncology, pathology, and others. This realization led to the formation of the GOG, which is a cooperative group of institutions, each represented by a gynecologist, medical oncologist, pathologist, and related specialists, one of whom serves as the Principal Investigator in the institution. The G O G conducts controlled clinical trials involving all accepted and experimental treatment methods in a large number of patients with all types of gynecologic cancer. It is also involved, to a limited extent, in laboratory research that fits into the multi-institutional framework of the group. It is hoped that through this cooperative effort answers can be obtained to outstanding questions in gynecologic oncology within a reasonable period of time, including those otherwise not readily obtainable from an single institution. The structure of the G O G consists of the Group Membership, an Operations Office, and committees (Fig. 1).
GIR~ ST~C~Z
N?[ ~ERATICt+SOFFICE
/
\
GROUP ~zI~ERSHIP
GOG COM~ITfEES
FIGURE 1 1 Protocol Chairman, G O G Group Chairman (1970-1975). 251 Copyright (~) 1975 by Academic Press, Inc. All rights of reproduction in any form reserved.
252
M. M. HRESHCHYSHYN
The Executive Committee, elected by the membership, is the policy-recommending body for the G O G , and the group membership, which meets twice a year, is the decision-making body. The Operations Office fulfills its administrative and statistical needs. Any institution with demonstrable potential to contribute to the studies of the group may apply for membership. At the present time, only institutions in the United States are eligible as members of the G O G for direct support by the National Cancer Institute. A new member remains in probationary, or provisionary, status for at least 1 year before becoming eligible for full (voting) membership, provided that its contribution to the group activities has been found satisfactory. A full-member institution, however, may be placed back in the probationary category and its membership may be discontinued for lack of satisfactory performance. Since its inception, the G O G membership has increased from 10 to 34, 2 which provides a pool of approximately 4000 new invasive gynecologic cancer patients a year available for G O G studies. The Operations Office consists of the Chairman's Office, a Statistical Office, Pathology and Radiotherapy Repositories, and a central Endocrine Laboratory (Fig. 2). The group chairman is elected by the membership for a 5-year period. He is responsible for the administration of the G O G . In addition, there is an executive officer who performs the function of vice-chairman. The group's biostatistician is in charge of the statistical unit. The Pathology and Radiotherapy Repositories collect and store in the Operations Office histologic and radiotherapy material on all study patients. The materials are reviewed periodically by the Pathology and Radiotherapy Committees
STATISTICALOFF]CE
~OLOGY F~POSITORY
I
FIG. 2. GOG operations office. 2 Member institutions include the following. Brown Affiliated Hospitals, Duke University Medical Center, Emory University Clinic, George Washington University Medical Center, Georgetown University & Affiliated Hospital, Hahnemann Medical College Hospitals, Henry Ford Hospital, Hospital of the University of Pennsylvania, Louisiana State University Medical School, Milton S. Hershey School of Medicine, Mount Sinai School of Medicine, New York Medical College, Northwestern School of Medicine, Roswell Park Memorial Institute, Rush-Presbyterian-St. Luke's Medical Center, State University of New York at Buffalo, University of Alabama Hospitals & Clinics, University of California at Los Angeles, University of California at San Diego, University of Cincinnati, University of Colorado Medical Center, University of Indiana, University of Iowa Hospitals & Clinics, University of Kansas Medical Center, University of Miami School of Medicine, University of Mississippi Medical Center, University of North Carolina, University of Rochester Medical Center, University of Southern California at Los Angeles, University of Texas Health Science Center at Dallas, University of Texas Medical Branch at Galveston, University of Utah Medical Center, Walter Reed Army Medical Center, and Wayne State University School of Medicine.
TABLE 1 GYNECOLOGIC ONCOLOGY GROUP'S CURRENT STUDY PROTOCOLS No.
Protocol
1 Postoperative treatment of women with resectable ovarian cancer with RT or melphalan or no further treatment 2 Postoperative treatment of women with Stage III ovarian cancer by RT or melphalan either alone or in both sequences 3 Treatment of women with disseminated or recurrent advanced ovarian cancer with melphalan alone; in combination with 5-FU; in combination with 5-FU and dactinomycin; or with the combinations of cytoxan, 5-FU, and dactinomycin 4 Treatment of women with cervical cancer Stages IIIb and IV confined to the pelvis with hydroxyurea or placebo both in combination with RT 5 Study of the relationship between growth pattern and lymphangetic and Vascular involvement in women with Stage Ia cervical cancer 6 The study of peritoneal fluid cellular patterns in women with Stage Ia and Ib adenocarcinoma of the ovary included in Protocol No. 1 of the Gynecologic Oncology Group 7 The study of peritoneal fluid cellular patterns in women with Stage III or IV ovarian carcinoma treated in Protocol Nos. 2 and 3 of the Gynecologic Oncology Group 10 Treatment of women with malignant embryonal carcinoma and malignant teratomas without neural elements with a combination of dactinomycin, VCR, and cyclophosphamide (Phase II) 11 Treatment of women with malignant teratomas containing neural elements with a combination of dactinomycin, VCR, and cyclophosphamide (Phase II) 12 Treatment of women with ovarian germ cell tumors containing choriocarcinoma with a combination of dactinomycin, MTX, and chlorambucil (Phase II) 13 Treatment of women with mixed mesodermal tumors of the ovary with a combination of dactinomycin and VCR given concomitantly with RT followed by a maintenance regimen with cyclophosphamide (Phase II) 14 Treatment of women with malignant tumors of the ovarian stroma, such as granulosa cell cancers, granulosa thecal cell cancers, and arrhenoblastomas, with either a combination of dactinomycin, 5-FU, and cyclophosphamide or with RT (Phase II-III) 16 A randomized comparison of preoperative and postoperative irradiation in the treatment of women with Stage I, Grades 2 and 3 adenocarcinoma of the endometrium 17 Treatment of advanced adenocarcinoma of the endometrium with radiotherapy and progestin 18 Treatment of women with adenocarcinoma (and adenoacanthoma) of the endometrium FIGO Stage II by surgery, RT, or combinations of both 19 Exploratory celiotomy for surgical staging of cervical cancer 20 Randomized study of prophylactic adriamycin versus no adjuvant chemotherapy in Stage I and II uterine sarcomas 21 Randomized study of adriamycin versus adriamycin plus dimethyl triazeno imidazole carboxamide in advanced uterine sarcomas 23 Comparison of the therapeutic effects of adriamycin vs. ADM + VCR vs ADM + cyclopfiospfiamide in the treatment of advanced carcinoma of the cervix (modified Phase II-III)
Study chairman (men)
Dr. M. Hreshchyshyn Dr. S. Kaplan
D r . S. Kaplan
Dr. M. Hreshchyshyn
Dr. S. Sail
D r . L . McGowan
Dr. L. McGowan Dr. R. Slayton and Dr. M. Hreshchyshyn Dr. R. Slayton and Dr. M. Hreshchyshyn Dr. M. Hreshchyshyn and Dr. R. Slayton
Dr. R. Slayton and Dr. L. Brady
Dr. R. Slayton and Dr. L. Brady Dr. C. P. Morrow and Dr. P. DiSaia Dr. C. P. Morrow and Dr. P. DiSaia Dr. C. Cohen and Dr. S. Sail Dr. H. Averette Dr. G. Omura Dr. G. Omura Dr. H. J. Wallace and Dr. M. Hreshchyshyn
254
M. M. H R E S H C H Y S H Y N
Tt~RC~IT[ZES ADMINISTPATIVECO~II~EkS
E)~CUTI~ tI?~EE g~BERSHIPCO~ITI~E Ir/-L~3 Ca'fIIT~E pgJTOCOLF£VIEWCO~IT~E gJALIIY CONTROLCOr~IITEE
FIGURE 3
~AIT~TCOFRITTESS CHEPIOIHEP#~PYCOMMIIII~S Iff~NOLORVCO~MIITEE PATHOLOGYCOffIITIEE PADIOI~HEI~PYCEt~IITIEE
FIGURE 4
CO~NITCE 011 INVASIVEND PRE-IINASIVEpIALIGNNCIES OF THE CERVIX,VULVA/~IDVAGINA HIID~ETRIALC~CER COff~IT~ OVARIAI~Ca~!CERCO~ITIF_E SARCC~A COM~IITIEE
FIGURE 5
and the Radiologic Physics Center. The Radiologic Physics Center is also responsible for monitoring radiation equipment of the participating institutions. The Central Endocrine Laboratory performs assays for gonadotropins and steroids. In addition to the Executive Committee, there are a number of committees appointed by the chairman of the group. These can be divided into (a) administrative, (b) treatment, and (c) tumor committees (Figs. 3, 4, 5). The names of the committees are indicative of their functions. In general, the administrative committees evaluate and monitor the bylaws, membership, institutional contributions to G O G activities, protocol design, and quality of data. The treatment committees monitor the interdisciplinary input into the G O G and the quality of various treatments in ongoing studies. Tumor committees concern themselves with the need for studies in particular cancer types and the evaluation of ongoing studies. Clearly, the work of the various committees is interrelated, and joint sessions for purposes of resolving specific problems are not uncommon. Since the G O G was established, it has instituted 23 protocols, 19 of which (Table 1) are presently active, of various gynecologic tumor types and stages of the disease. Eleven of these protocols deal with ovarian, 4 with cervical, 3 with corpus carcinoma, and 2 with uterine sarcomas. In all, 2003 patients were entered into these s t u d i e s - approximately 1000 of them during the last year, which shows the rapid acceleration in the G O G studies. Some of these studies are close to completion, and we will be reporting our preliminary results soon. II. Treatment of Women with Cervical Cancer Stages IIIb and IV Confined to the Pelvis with Hydroxyurea or Placebo Both in Combination with Radiation Therapy
Results of an earlier study conducted by this investigator on the use of hydroxyurea in combination with radiation in the treatment of patients with advanced cervical carcinoma suggested that the combination is superior to radiotherapy alone, particularly in control of Stage IIIb of the disease [1]. The Gynecologic Oncology Group undertook to test these findings. Patients with primary squamous carcinoma of the cervix, Stage IIIb and IVa, were eligible. The protocol design is shown in Fig. 1. Randomization is carried out via the closed-envelope technique. Response to treatment is evaluated in terms of toxicity, changes in tumor mass, duration of progression-free interval, and patient survival. Analysis of the data was prepared by Dr. John Blessing,
255
GYNECOLOGIC ONCOLOGY REPORTS I AND II
Randomize 80 mg./kg, every 3 days/12 weeks
FH+ydroxyurea
REGIMENI [+ExternalIrradiation 5000 rads to the pelvis/5-8 week~ ~tracavitary Radium 3000 rads to Point A
+~acebo
80 mg./kg, every 3 days/12 weeks
~REGIMEN II [+External Irradiation
5000 rads to the pelvis/5-8 weeks
L~tracavitary Radium 3000 fads to Point A
Fro. 1. GOG protocol # 4. Treatment of women with cervical cancer Stages IIIb and IV confined to the pelvis with hydroxyurea or placebo both in combination with radiation therapy.
TABLE 1 PATIENT ENT~ES
Treatment
No. entered
No. excluded
No. eligible
No. evaluable for toxicity
No. evaluable for survival
130 121 251
26 26 52
104 95 199
82 78 160
84 83 167
I
II Total
TABLE 2
REASON FOR EXCLUSION BY TREATMENT Treatment Reason for exclusion
I
II
Ineligible Protocol violation Refused treatment Removed by investigator Clerical error Other Total
5 6 11 2 1 1 26
16 4 5 0 1 0 26
TABLE 3 ToxICITY BY TREATMENT (SUMMARY) Chemotherapy
Radiotherapy
RX
No. evaluated
WBC < 3000 platelets
or
