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Biomedical subjects

R S Cox

Publications and source records attributed to R S Cox.

At least 91 records · Page 5Linked to original sources

Analysis of non-Hodgkin's lymphomas with nodular and favorable histologies, stages I and II.

Between 1961 and 1980, 124 patients with Stages I and II nodular lymphocytic poorly differentiated (NLPD), nodular mixed histiocytic-lymphocytic (NM), nodular histiocytic (NH), or diffuse well-differentiated lymphocytic (DLWD) lymphoma according to the Rappaport classification were treated at Stanford University. Initial staging studies included lymphangiography in 91%, bone marrow biopsy in 93%, and diagnostic or staging laparotomy in 41% of patients. All patients were treated with megavoltage irradiation to either involved field (IF), extended field (EF), or total lymphoid fields (TLI) to a total dose of 3500-5000 rad. Median follow-up was 5.5 years. Kaplan-Meier actuarial survival at 5, 10, and 15 years was 84%, 68%, and 42%, respectively. Freedom from relapse at 5 and 10 years was 62% and 54%, respectively. In addition, there was a flattening of the relapse curve suggesting cure of approximately 50% of patients. Patients with NH had a significantly poorer survival (P = 0.03) while there were no differences among the other histologic groups. Freedom from relapse was higher in patients treated with TLI compared with those treated with IF or EF. However, a prospective study of 20 patients who all underwent staging laparotomy and were randomized to treatment with either IF or TLI revealed no significant difference in either survival or freedom from relapse. Utilizing multivariate analysis for the entire group, important prognostic factors included age, stage, histologic subtype, and treatment field.

Adolescent↗

Adenocarcinoma of the endometrium. Analysis of 256 cases with disease limited to the uterine corpus: treatment comparisons.

Between 1959 and 1975, 256 patients with pathologic Stage I uterine adenocarcinoma were treated at Stanford University Hospital, Stanford, California. One hundred ninety-three patients were initially treated with surgery, and 63 received preoperative radium, reflecting different treatment philosophies of physicians operating at Stanford. Relapse rates for the two treatment groups were 9% (17 of 193) and 14% (9 of 63), respectively (P = 0.24). In both groups of patients, relapse rates were correlated with grade, although for those treated with initial surgery myometrial invasion was a much better predictor of relapse. Only one of the 127 patients without demonstrable myometrial invasion suffered a possible relapse. Sixteen of 66 patients with myometrial invasion (24%) relapsed after treatment. A review of the histologic material revealed 26 of 256 cases with a special histologic variant termed uterine papillary serous carcinoma, which was associated with a high relapse rate (50%) and a marked tendency for upper abdominal spread. It was found that the use of preoperative intracavitary radium was not demonstrated to be of value. Histologic information obtained from the hysterectomy specimen can be used to determine patients at high risk for relapse who may benefit from adjuvant treatment based on our understanding of the natural history of endometrial carcinoma.

Adenocarcinoma↗

Hodgkin's disease limited to intrathoracic sites.

The records of 1470 patients treated for Hodgkin's disease between 1960 and 1980 were reviewed, and sites of initial involvement were scored. Forty-four patients had disease limited to the chest after clinical and/or pathologic staging. Eighteen asymptomatic patients underwent a staging laparotomy and no occult subdiaphragmatic disease was identified. All 44 patients were treated with irradiation (XRT) to involved (IF), mantle (M), subtotal lymphoid (STLI), or total lymphoid (TLI) fields. Eighteen patients were also treated with chemotherapy, consisting of nitrogen mustard, vincristine, and procarbazine, with or without prednisone (MOP(P)), or procarbazine, melphalan, and vinblastine (PAVe). With a median follow-up of 7.5 years the survival at five and ten years was 93% and 89%, respectively, and the freedom from relapse (FFR) at five and ten years was 81% and 78%, respectively. Ten patients relapsed, all in supradiaphragmatic sites (including six relapses within lung parenchyma). Eight had initially received XRT alone, and two had received combined modality treatment. The risk of relapse in the 26 patients treated with XRT alone varied inversely with the volume irradiated: IF, 100% (3/3); M, 45% (3/7); STLI, 17% (2/12); TLI, 0% (0/4) relapsed. Seven of the eight relapsing patients treated with XRT alone were salvaged with subsequent XRT and/or chemotherapy whereas both of the combined modality patients who relapsed, died with progressive disease despite all salvage therapy.

Antineoplastic Agents↗

125Iodine implants as an adjuvant to surgery and external beam radiotherapy in the management of locally advanced head and neck cancer.

125Iodine seeds either individually placed or inserted into absorbable Vicryl suture carriers were utilized in conjunction with surgery and external beam radiotherapy in an attempt to increase local control rates in patients with (1) advanced oropharyngeal and laryngopharyngeal cancers (T3-T4, N2-N3), (2) massive cervical lymphadenopathy (N3) and an unknown primary site and (3) locally recurrent head and neck cancers. Forty-eight patients were treated with 55 implants. The carotid artery was implanted in 15 patients, while seven patients had seeds inserted into the base of the skull region, and another three patients had implants near cranial nerves. Eighteen of the 48 patients were treated for cure. The actuarial survival at five years in this subgroup was 50%. The overall local control in the head and neck area was 58%. In this group no patients to date have had a local failure in the implanted volume. Seventeen patients with comparable stage of disease treated prior to 1974 with curative intent without 125I implants were analyzed retrospectively for comparison with the implanted patients. The actuarial survival of these patients was 18% and the overall head and neck control was 21%. These differences are statistically significant at a P value of 0.01 and 0.007, respectively. Seventeen patients received implants for local recurrence. The local control in the head and neck area was 50%; however, the 2.5 year actuarial survival was only 17%. The complication rate was 11% (six of 55 implants). The improved survival, the high local control, and the minimal complication rates in this series makes the intraoperative implantation of 125I seeds and effective adjunctive treatment to surgery and external beam irradiation.

Brachytherapy↗

Lower abdominal radiotherapy for stages I, II, and selected III epithelial ovarian cancer: 20 years experience.

Between 1956 and 1975, lower abdominal radiotherapy was administered as primary postoperative treatment to 82 patients with stages I, II, and selected III epithelial ovarian carcinoma and with varying amounts of postoperative residual disease. The median follow-up was 7.5 years, and the overall freedom from relapse (FFR) at 10 years for the entire group was 57%. The FFR at 10 years for stages I, II, and III was 78, 60, and 24% respectively, and these results are better than published series of similarly staged patients treated with surgery alone. Ten-year FFR was 79% for patients with no residual disease (NRD), 49% for patients with minimal residual disease (MRD) of less than 2 cm, and 24% for patients with gross residual disease (GRD) of greater than 2 cm. Control within the irradiated lower abdomen was achieved in 97% of patients with NRD, 84% of patients with MRD, and in 55% of those with GRD. Of all relapses, 33% occurred in the pelvis (almost all in patients with GRD), 37% in the untreated upper abdomen, 21% in distant sites, and 9% had an undetermined intraabdominal site of relapse. Among those patients with stage I and II disease or favorable residual tumor (NRD and MRD), approximately 50% of relapses occurred in the untreated upper abdomen alone.

Female↗

The use of para-aortic radiation therapy based on lymphangiogram interpretation in uterine cervical carcinoma.

From January, 1965, to June, 1979, 79 nonrandomized patients with carcinoma of the uterine cervix had a bipedal lymphangiogram (LAG) prior to radiotherapy at the Stanford University Medical Center. In 32 patients the LAGs were interpreted as normal. Of the remaining 47 patients, 28 had LAGs interpreted as positive for metastatic involvement of pelvic nodes alone, 11 as positive for pelvic and para-aortic (PA) metastasis, and 8 as positive in PA nodes alone. Five-year survival and freedom from relapse (FFR) were found to be similar for patients with LAGs interpreted as normal or positive in pelvic nodes only (all stages combined). The addition of elective PA irradiation in those patients with positive pelvic nodes alone (median 5000 rad/5 weeks) did not enhance either survival or FFR in this group. The 19 patients with positive PA nodes had significantly worse survival and FFR when compared with the other groups. Survival was not enhanced by the addition of therapeutic PA irradiation (median 5000 rad/5 weeks) and the 7 patients in this group so treated appeared to have a reduced FFR when compared to the 12 untreated patients. Irrespective of the location of nodal abnormality on LAG and regardless of stage, the majority of relapses (16/23) occurred either centrally or at the pelvic sidewalls. It is concluded that the LAG is a good predictor of subsequent relapse and survival, but that the addition of either elective or therapeutic PA radiotherapy based on LAG interpretation does not affect survival of FFR and should, therefore, be considered for investigational or palliative use only.

Adenocarcinoma↗

Extramedullary lesions in non-lymphocytic leukemia: results of radiation therapy.

Fifty-four courses of radiotherapy were given to 33 patients with symptomatic extramedullary involvement by non-lymphocytic leukemia. Among them were 23 cases of granulocytic sarcoma. Analysis of the treatment response showed that age, hematopathologic type and quality of irradiation did not influence the radiation response. However, a dose response relationship could be demonstrated with a statistically significant difference in response among the four groups of patients treated to total doses of less than 1000 rad, 1000-1999 rad, 2000-2999 rad, and greater than or equal to 3000 rad (p = 0.003). We suggest irradiating all extramedullary lesions to at least 1100 ret.

Acute Disease↗

Analysis of cosmetic results and complications in patients with stage I and II breast cancer treated by biopsy and irradiation.

Between May, 1973 and December, 1980, 78 Stage I and II breast carcinomas in 76 patients were treated by biopsy and radiotherapy with curative intent. With a maximum follow-up of 10 years, a minimum of 2 1/2 years and a median follow-up of 3 1/2 years, a loco-regional control rate of 97% was obtained. Cosmetic results and treatment complications were studied. Patient characteristics, tumor size, excisional biopsy technique, axillary staging procedure and radiotherapy techniques were analyzed and all found to be important factors affecting cosmesis and complications. The most common complications included transient breast edema observed in 51% of patients, breast fibrosis (usually mild) seen in 23% of the population, axillary hematoma or seroma formation in 15%, mild arm edema in 14% and basilic vein thrombosis in 10% of patients. The causes of these and other less frequent complications are discussed. The overall cosmetic result was excellent in 78%, satisfactory in 18% and unsatisfactory in 4% of patients. Recommendations for improving cosmetic results minimizing complications are made. In our prospective trial, the high loco-regional control and good cosmesis supports the use of excisional biopsy and radiation therapy in patients with Stages I and II breast carcinoma.

Adenocarcinoma↗

Survival, prognostic factors, and relapse patterns in uterine cervical carcinoma.

Between 1965 and 1979, 295 evaluable patients were treated with radiotherapy and/or surgery for invasive cervical carcinoma at the Stanford University Medical Center. The records of these patients were analyzed retrospectively with regard to survival, possible prognostic factors of freedom-from-relapse, and relapse patterns. Survival for the entire population at 5 years was 67%, with a median follow-up of 5 years. Five-year freedom-from-relapse (FFR) rates for stages I-IV were 88%, 61%, 33%, and 11%, respectively. Eighty-eight percent of all relapses occurred within 5 years. Several possible prognostic factors of FFR--including stage, histology, tumor differentiation, lymphangiogram status, treatment modality, age, presence of cervical stump, and initial serum hemoglobin value--were evaluated with a multivariate analysis. Stage was the best predictor of FFR, and lymphangiogram (LAG) status was the next most important covariate: 13 of 19 patients who showed involvement of paraaortic nodes on LAG relapsed within 1 year. There was no difference in survival or FFR between adenocarcinoma or squamous cell histologies. FFR in stage IB patients was independent of treatment modality; i.e., radiotherapy alone, surgery alone, or combined therapy. Initial serum hemoglobin (less than 12 vs. greater than 12) was not predictive of FFR or survival. Stage for stage, patients over 57 years of age tended to have better FFR than younger patients. The majority of relapses occurred centrally or at the pelvic sidewalls (58%), and future attempts to improve local control rates will rely more heavily on the individualized use of interstitial template applicators.

Adenocarcinoma↗

Histologic conversion in the non-Hodgkin's lymphomas.

Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkin's lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkin's lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.

Actuarial Analysis↗

Extralymphatic involvement in diffuse non-Hodgkin's lymphoma.

Between 1961 and 1982, 543 patients with diffuse histiocytic, mixed, or undifferentiated lymphoma were treated at Stanford University, Stanford, Calif. Of this group, 281 (52%) had extralymphatic lesions and the 111 patients with stage IE and IIE disease were subjected to analysis. Most patients (94) had diffuse histiocytic lymphoma. Lymphangiography was performed in 77%, bone marrow biopsy in 91%, and diagnostic or staging laparotomy in 52% of the patients. All but five patients were treated with megavoltage irradiation and 35 patients received combination chemotherapy. Median follow-up was 4.0 years. Kaplan-Meier actuarial survival at five and 10 years was 46% and 36%, respectively. Freedom from relapse (FFR) at five years was 49% with no relapses beyond that point. The most common extralymphatic sites were the gastrointestinal tract, the head and neck region, and the lung. Prognosis could not be correlated with the specific sites of involvement. Patients with bulky disease (greater than 10 cm) or more than three sites of involvement had a significantly lower survival and FFR. There was no significant difference in outcome for patients treated with irradiation or combined modality therapy. Most patients (62%) relapsed in distant extralymphatic sites.

Actuarial Analysis↗

Primary mucinous adenocarcinoma of the endometrium. A clinicopathologic and histochemical study.

Of 256 patients with carcinoma confined to the uterine corpus at the time of hysterectomy treated in the period 1959-1975 at Stanford University Hospital, 98 patients (38%) had neoplasms which demonstrated at least focal intracytoplasmic mucin. In 21 carcinomas (9%), intracytoplasmic mucin production was the dominant form of differentiation--a group which we designate primary mucinous carcinoma of the endometrium. Freedom from relapse and frequency of myometrial invasion were not statistically different for patients whose neoplasms contained intracytoplasmic mucin, regardless of the amount of mucin present, when compared with cases of nonmucin-containing carcinoma. Using histochemical methods, it was impossible reliably to distinguish between the intracytoplasmic mucin produced by carcinomas arising in endometrium and that produced by carcinomas primary in the endocervix. Differential biopsy and fractional curettage are stressed as useful tools in making this clinically important distinction. Since both benign mucinous metaplasia and mucinous carcinoma may arise in the endometrium, it is important to establish histopathologic criteria by which the malignant lesions may be recognized. The use of criteria illustrated in this paper (which include architectural complexity of proliferation, epithelial stratification, loss of epithelial polarity, and nuclear atypicality) resulted in the recognition of mucin producing proliferations which as a group manifest a 50% incidence of myometrial invasion.

Adenocarcinoma↗

Breast edema following staging axillary node dissection in patients with breast carcinoma treated by radical radiotherapy.

Seventy-four patients with carcinoma of the breast were treated by irradiation without a mastectomy at Stanford between May 1973 and March 1980. Seventy-six breasts were treated because two patients had bilateral simultaneous cancers. Breast edema was noted in 41% of these cases. Analysis of potential predisposing factors revealed that this complication occurred primarily in patients who received a staging axillary lymph node dissection. Lymphedema occurred in 26 of 33 breasts (79%) in patients who had staging axillary dissections; this complication developed in only three of 12 (25%) with axillary samplings and two of 31 (6%) with no axillary surgery. Two groups of patients were identified: (1) 28 patients whose breast edema occurred early (prior to or during radiation therapy), and (2) three patients with late onset edema that developed several months postirradiation. The early edema, which is clearly related to axillary lymph node dissection, gradually improved during the follow-up period with complete or near complete resolution expected by three years. Late onset edema was rare, appears to be related to an axillary radiation dose greater than 5500 rad, and may be irreversible. There was no correlation of breast edema with tumor stage, radiation time/dose factors, the use of bolus, patient weight, or breast size.

Adult↗

The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience.

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.

Adult↗

Prognostic factors in pathological stage IIIA Hodgkin's disease.

From July 1968 through December 1977, 171 previously untreated patients with pathological stage IIIA Hodgkin's disease were evaluated at Stanford University Medical Center. All patients underwent lymphography, staging laparotomy and splenectomy; 86 patients were treated with total lymphoid irradiation (mantle followed by inverted-Y) to 4400 rad. These patients received prophylactic irradiation to the preauricular region (3600 rad/4-5 wk.) if the high cervical lymph nodes were positive; the lung (1500 rad/4-5 wk.) if the ipsilateral pulmonary hilum was positive; and the liver (2200 rad/5-6 wk.) if the spleen was positive. Eighty-five patients were treated with total lymphoid irradiation followed by adjuvant chemotherapy-either nitrogen mustard, vincristine and procarbazine (MOP) or procarbazine, L-phenylalanine mustard, and vinblastine (PAVe). Five-year survival rates were not significantly different in the two groups (86% vs. 89%, P = .4); however, the five-year freedom from relapse rate was significantly better in the combined modality group (66% vs. 86%, P = .0026). Because of the success of MOP in the treatment of patients who had relapses after treatment with irradiation alone, the five-year freedom from second relapse rates in the two groups were not significantly different (85% vs. 88%, P = .8). Analysis of a large number of possible prognostic factors failed to identify any subgroup of patients whose survival was significantly improved by the use of adjuvant chemotherapy, including patients with "anatomic substage III2" (P = .52), clinical stage III (P = .26), unfavorable histology (P = .78), age greater than 39 yr. (P = .44), males (P = .55), and S- (P = .92). The most important factors indicating a benefit from adjuvant chemotherapy on survival were greater than or equal to 5 sites of involvement, including those above and below the diaphragm (P = .15) and extensive splenic involvement (more than four nodules detected in the splenectomy specimen) (P = .15). Possible explanations for these observations, which differ from those of series reported at other institutions, are discussed.

Adult↗