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J D Cox

Publications and source records attributed to J D Cox.

At least 181 records · Page 10Linked to original sources

Advanced carcinoma of the nasopharynx. 2. Pattern of failure in 256 patients.

Of 256 patients with advanced carcinoma of the nasopharynx, 82% presented with Stage IV disease. The 5-year survival was 15% with 83% failing within 2 years. Prognosis was related to stage (p less than 0.03), neck status (p less than 0.03), initial performance status (p less than 0.001) and radiation dose (p less than 0.003). With no pathological neck glands (N0), less than 5% failed radiotherapy. Overall, 36% had distant metastases, correlating with the N Stage (p less than 0.001) but not with the T Stage. The most frequent site of metastasis was lung, then bone and liver. Radical neck dissection failed to increase tumor control, contributing to three fatal complications. New radiotherapeutic regimens have so far failed to substantially improve the results.

Adult↗

Characteristics of long-term survivors after treatment for inoperable carcinoma of the lung.

Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirmed inoperable or unresectable carcinoma of the lung of all cell types were treated with curative intent. Forty-five patients lived a minimum of 3 years and 32 patients lived 5 or more years. The 3-year survival rate increased from 7.6% (15/197) between January, 1971 and June, 1975 to 14.1% (30/213) for the interval from July, 1975 to August, 1978 (p less than 0.01). Factors associated with long-term survival were performance status (p less than 0.01), early stage (p less than 0.001), high total dose of radiation (p less than 0.02), large cell carcinoma (p less than 0.01), inoperable for medical reasons (p less than 0.001), and thoracotomy to determine unresectability (p less than 0.04). The difference in survival rates between the two time periods was not related to different patient factors. Survival rates were most improved in the second time period for patients with Stage II or Stage III carcinoma of the lung. Eight patients died from cancer between 36 and 54 months of initial treatment. Five patients died of intercurrent disease without evidence of cancer of the lung after 3 years. An increasing proportion of long-term survivors of inoperable carcinoma of the lung can be expected to result from a better understanding of these diseases, more technically sophisticated external irradiation, and the use of combination chemotherapy for small cell carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Multiagent chemotherapy, prophylactic neuraxis irradiation, and consolidative irradiation for small cell carcinoma of the lung.

Between 6/81 and 6/83, 73 patients with small cell carcinoma of the lung were treated according to a prospective protocol in which cyclophosphamide, doxorubicin, and vincristine (CAV) were given concurrently with prophylactic craniocervical irradiation to the level of C5. Both limited and extensive disease patients with normal computed tomography of the brain received 25 Gy in 10 fractions in 2 weeks. Complete responders to CAV received consolidative thoracic irradiation (CTI) to the local-regional primary (37.5 Gy in 15 fractions in 3 weeks), the first 25 Gy in 10 fractions serving as prophylaxis of the C6 to T12 spinal cord. The neuraxis from L1 to S2 then received 25 Gy in 10 fractions in 2 weeks. Consolidative irradiation of localizable metastatic sites was given in extensive disease patients. Partial and nonresponders to CAV received 50-60 Gy in 5-6 weeks to local-regional disease. With a median followup of 29 months, survival was significantly better (p less than .01) in patients receiving CTI to the chest after complete response to CAV (both limited disease and extensive disease) than without CTI. Of 41 patients completing the protocol and without central nervous system (CNS) involvement at presentation, four (9%) failed initially in the CNS (two brain, two spinal axis); CNS failure was the cause of death in all four patients with no other sites of metastases at death in two of these. Failure to complete protocol treatment was due to disease progression during chemotherapy in 25/73 (34%) and chemotherapy related complications (three sepsis, one gastrointestinal bleed) in four of 73 (5.5%) patients. CTI and prophylactic neuraxis irradiation did not increase morbidity or result in mortality in the sequence utilized; prophylactic neuraxis irradiation appears to reduce the CNS relapse rate, and CTI benefits survival.

Actuarial Analysis↗

What is the lowest effective biologic dose for prophylactic cranial irradiation?

Between January 1974 and September 1984, 327 consecutive patients with small cell carcinoma of the lung (SCCL) free of clinical and brain scan (radionuclide or computed tomography) evidence of brain metastasis were treated at the Medical College of Wisconsin Affiliated Hospitals. All patients received single agent chemotherapy, consisting of cyclophosphamide or methotrexate (1974-1975), or combination chemotherapy with cyclophosphamide, doxorubicin, and vincristine with or without methotrexate and leukovorin (1976-1984). Between January 1974 and December 1974, 82 patients were treated with chemotherapy without prophylactic cranial irradiation (PCI). Between 1978 and 1984, all patients received PCI during the first week after diagnosis, simultaneous with their first cycle of chemotherapy. Chest irradiation was given to the complete responders to the chemotherapy. During the first 31/3 years of the study with PCI (January 1978-May 1981), 51 patients received 30 Gray (Gy) in 10 fractions in 2 weeks and five of them (10%) developed brain metastasis. Thereafter, 25 Gy in 10 fractions was consistently administered for PCI. Six of 194 patients (3%) developed brain metastasis. The cumulative (time corrected) probability of brain metastasis was approximately 10% at 1 year and was similar for patients who received 25 Gy and those who received 30 Gy. Although detailed neuropsychological testing has not been performed, clinically apparent late sequelae that might be attributed to PCI have not been seen. Nonetheless, the dose fractionation regimen of 25 Gy in 10 fractions with combination chemotherapy, cyclophosphamide, doxorubicin (or methotrexate), and vincristine is as effective in eliminating subclinical metastasis to the brain. It can be recommended for future trials until more data become available about late sequelae of treatment of SCCL and the patient characteristics and treatment factors that may contribute.

Actuarial Analysis↗

Cutaneous lymphoid hyperplasia: results of radiation therapy.

Four cases of cutaneous lymphoid hyperplasia (CLH) were treated with radiation therapy. Sixteen separate areas of the skin were irradiated. Only two received more than 18 Gy (1,800 rad). Follow-up ranged from eight months to seven years. No infield recurrences were observed, and cosmetic results were excellent. The authors suggest that radiation therapy can be highly effective in the treatment of CLH.

Adult↗

Malignant lymphoma of the uterine cervix.

Three patients with primary malignant lymphoma of the uterine cervix are reported and the literature is reviewed. All of the patients in the current cases presented with irregular menstruation. Two patients were found to have diffuse histiocytic lymphoma, and one patient had diffuse mixed lymphoma. Histologic diagnosis was confirmed by outside expert pathologists in all cases. In spite of locally advanced disease according to FIGO's classification (Stage IVA-2 and Stage IIB-1), they responded well to external irradiation, and had control of tumor within the pelvis. All are alive at 13, 7, and 3 years, respectively, after the completion of irradiation. One patient developed disseminated disease 4.25 years after the completion of external irradiation, but was successfully treated with combination chemotherapy for 2 years, and is alive at 6.75 years after the completion of chemotherapy without disease. Review of the other 21 cases reported in the literature reveals that 14 were free of disease after treatment. The importance of distinguishing malignant lymphoma from undifferentiated carcinoma or sarcoma is emphasized since cervical malignant lymphoma can be successfully treated with irradiation in spite of locally advanced disease.

Adult↗

Single and double plane implants: a comparison of the Manchester System with the Paris System.

A comparison between the Manchester System and the Paris System of interstitial dosimetry has been made in the case of single and double plane implants. The rules of both systems are reviewed. A brief description of the Paris System is presented in an appendix. Dose distributions for two different examples are presented in two orthogonal planes. The Paris System uses considerably fewer sources than the Manchester System. It results in a larger volume of high dose than the Manchester System. The use of Iridium-192 sources strength and source length can be adjusted represents a significant advantage. The Paris System attempts to adapt the implant configuration to the clinical situation as the target thickness is used to define the source separation and the target length is used to define the source length. The differences in the dose definition are discussed.

Brachytherapy↗

The prognostic significance of histologic subtyping in small cell carcinoma of the lung.

Previously untreated patients with small cell carcinoma of the lung (SCCL), who were treated at the Medical College of Wisconsin with combined chemotherapy and radiation therapy, were retrospectively subtyped according to the 1981 World Health Organization Lung Cancer Classification. Of 54 evaluated patients, 27 (50%) had "oat cell" subtype, 22 (41%) "intermediate cell" variety, and five (9%) were classified as "combined" type. There was no significant difference in response to therapy or median survival between the subtypes. In addition to the absence of prognostic significance among the subtypes, there were many technical factors affecting accuracy of subtyping, including tissue-crushing artifacts, size of biopsy materials, fixation of tissue samples, and variation of subtypes within the same biopsy. We conclude that subtyping of SCCL should not be construed as a prognostic tool or guideline to therapy. However, the recognition that SCCL may manifest in a variety of histologic patterns, some of which may be misinterpreted as a histology other than SCCL, is probably more important for choice of therapy and prognosis than the individual subtypes.

Carcinoma, Small Cell↗

Influence of preoperative irradiation on failures of endometrial carcinoma with high risk of lymph node metastasis.

From 1965-1980, 80 patients with adenocarcinoma of the endometrium, FIGO-AJC Stage I, Grade 3 and Stage II received preoperative radiation therapy. Thirty-three patients had Stage I, Grade 3 and 47 had Stage II. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. They were followed from 3-18 years (median, 6.2 years) after the completion of treatment and none was lost to follow-up. Overall 5-year actuarial disease-free survival was 75%. Preoperative external whole pelvic plus intracavitary irradiation gave the best 5-year survival of 83%; there were no failures after 20 months. In comparison to this group, survival for the intracavitary alone group was 64% at 5 years and 54% at 8 years. The 5-year survival of Stage II was 81% compared to 66% of the Stage I, Grade 3 group. Prognostic variables were analyzed and showed that the residual tumor in the specimen at the time of surgery after the preoperative irradiation was significantly correlated to a worse prognosis: patients who were found to have no residual tumor had a 5-year survival rate of 96% compared to 65% of those who were found to have residual tumor (p less than 0.01). Age, stage, methods of preoperative irradiation, dose of external pelvic irradiation or intracavitary application were not statistically significant prognostic factors. The grade of the tumor was suggestive as a prognostic variable. The most common failure site was the para-aortic lymph nodes independent of treatment methods and stage. Four patients developed complications possibly related to the radiation therapy. Our study suggests that preoperative external and intracavitary irradiation reduces the frequency of residual microscopic carcinoma and improves survival for patients with Stage I, Grade 3 and Stage II carcinoma of the endometrium.

Adenocarcinoma↗

Do prostatic biopsies 12 months or more after external irradiation for adenocarcinoma, Stage III, predict long-term survival?

Serial biopsies of the prostate after high dose external irradiation for adenocarcinoma show a gradual disappearance of the neoplastic cells. With such treatment, results of the biopsies do not have any short term prognostic significance. However, positive biopsies 12 months or more after treatment are reputed to be an unfavorable sign for long-term survival. From August, 1970 through February, 1974, 46 consecutive patients with locally advanced (Stage III, C, or T3 and T4) adenocarcinoma of the prostate underwent external irradiation with 2 MV X rays or cobalt-60 teletherapy. The technique included parallel, opposed, 14 X 14 cm anterior and posterior fields, and a 10 X 14 cm perineal field. The center of the prostate received a total dose of 70 Gy in 30-37 fractions in 43 to 56 days. Details of the dosimetry reveal inhomogeneity of the dose of +/- 7% within an enlarged prostate. With a median follow-up of 8 years, the actuarial survival rates, uncorrected for death from intercurrent disease, are 69% at 5 years and 49% at 10 years. Biopsies of the prostate 12 months or more after treatment were available from 31 patients: 19 had one or more positive biopsies and 12 had consistently negative biopsies; the survival curves are identical for those with and those without positive biopsies. Prostatic biopsies obtained 24 months or more after treatment were available from 21 patients: 10 had positive and 11 had negative biopsies; the survival curves are identical for those with and without residual cancer cells. Following adequate irradiation of patients with locally advanced adenocarcinoma of the prostate, the results of biopsies obtained one or two years after treatment do not predict long-term survival.

Adenocarcinoma↗

Frequency of brain metastasis in adenocarcinoma and large cell carcinoma of the lung: correlation with survival.

From January 1970 through December 1981, 469 patients with histologically or cytologically proven adenocarcinoma (AC) (349) and large cell carcinoma (LC) (120) of the lung were seen at the Department of Radiation Oncology, Medical College of Wisconsin Affiliated Hospitals. One quarter (126/469) of these patients had brain metastasis: 48 patients presented with brain metastasis (AC 35/349 = 10% and LC 13/120 = 11%) and 78 patients subsequently developed brain metastasis (AC 61/314 = 19%, LC 17/107 = 16%). Those patients who received prophylactic cranial irradiation were excluded from this study. Brain was the dominant site of metastasis in 82 patients who received only cranial + thoracic irradiation; 37 patients (17 simultaneous, 20 metachronous) also required irradiation of other sites of metastasis. All 17 patients with LC, and 47/61 (77%) with AC who developed metachronous brain metastasis did so within one year. The cumulative probability of brain metastasis increased with survival to the levels predicted by autopsy studies. Therapeutic brain irradiation may result in long-term survival in patients with single organ brain metastasis. Three of 119 patients who underwent whole brain irradiation for metastasis, are alive at 60 (LC), 48 (AC) and 48 months (AC) after treatment. Since patients with AC and LC so frequently develop brain metastasis and the brain may be the only site of metastasis, prophylactic cranial irradiation may significantly reduce morbidity and mortality from these diseases.

Adenocarcinoma↗

Internal mammary lymphoscintigraphy in patients with breast cancer. Correlation with computed tomography and impact on radiation therapy planning.

Twenty patients with Stage I or II breast cancer, all of whom had undergone radiation therapy planning, were examined with internal mammary lymphoscintigraphy (IMLS) and computed tomography (CT). Based on the results of IMLS, radiation fields were revised in 12 cases (60%). The mean number of nodes identified by IMLS in each patient was 7.8, which is in agreement with previously published autopsy and scintigraphic data. CT identified 243 possible nodes of normal size, but only 49 of them were within 10 mm of regions shown to be positive on the scintigram. The authors conclude that IMLS is the method of choice for defining parasternal lymphatic drainage and identifying those internal mammary nodes that are normal in both size and function.

Adult↗

Role of radiation therapy in small cell anaplastic carcinoma of the lung.

The previously established roles of radiotherapy in the management of small cell anaplastic carcinoma of the lung have changed with the development of improved chemotherapy. A group of the International Association for the Study of Lung Cancer has concluded that while there is established evidence that the addition of chemotherapy improves the results of radiation therapy, the value of the addition of loco-regional radiation therapy to chemotherapy is uncertain and more difficult to assess. No advantage in short-term (median) survival has been shown in randomized studies, but current data suggest a possible advantage in long-term control of loco-regional disease. Further results of prospective trials are needed to resolve this question. Prophylactic cranial irradiation reduces the incidence of cerebral metastases but so far has not resulted in improved survival. Pending the results of further randomized studies, its routine use in all patients is not advocated. The palliative role of radiation therapy is valuable in symptomatic treatment. Various current modifications of technique to improve the results of conventional radiation treatments with an altered fractionation schedule and use of sensitizers and large fields are not believed to show major advantages. The clear documentation of treatment details and the definition of the criteria for the assessment of results are important if further comparisons of results are to be made possible. In particular, the need for reporting long-term survival at 2 years in contrast to the more usual median survival time is stressed.

Antineoplastic Agents↗

Is immediate chest radiotherapy obligatory for any or all patients with limited-stage non-small cell carcinoma of the lung? Yes.

External irradiation with the greatest technical sophistication available is indicated in all patients with inoperable non-small cell carcinoma of the lung confined to the primary site and to regional lymph nodes including the ipsilateral supraclavicular nodes. Irradiation with moderately high doses results in responses in 40%-65% of all patients. With irradiation to a level of at least 6000 rad in 30 fractions in 6 weeks, greater than 60% of patients never fail in the chest. Some of these patients become long-term, disease-free survivors. Until it is possible clearly to predict those patients who do not respond and thereby to justify an approach other than thoracic irradiation, it is necessary to offer radiation therapy to all of these patients. Since local control is far from satisfactory, one can certainly justify investigating new approaches, including further increases of the total dose, altered fractionation schemes, addition of radiosensitizers, and high linear energy transfer radiations. Since distant metastases frequently appear in spite of thorough pretreatment evaluations, one can also justify investigating the addition of systemic agents, both cytotoxic drugs and biologic response modifiers. Benefit from these systemic approaches may be completely masked, even in patients with disseminated disease, by failure to prevent complications and death due to the intrathoracic tumor.

Adenocarcinoma↗

Changes in the relative risk and sites of central nervous system metastasis with effective combined chemotherapy and radiation therapy for small cell carcinoma of the lung.

Prolongation of survival of patients with small cell carcinoma of the lung with current effective systemic therapy has been accompanied by a marked increase in the frequency of relapse in the central nervous system (CNS). Prophylactic cranial irradiation (PCI) was shown to reduce the frequency of brain metastasis, but there was no increased short-term survival. Therefore, the necessity for PCI early in the course of treatment has been questioned, especially for patients with extensive disease. From January 1974 through March 1982, 205 patients with small cell carcinoma of the lung were treated at the Medical College of Wisconsin Affiliated Hospitals. None had clinical, radioisotopic, or computed tomographic evidence of brain metastasis. Eighty-two patients received radiotherapy and chemotherapy, but no PCI; 123 patients received combination chemotherapy and radiation therapy with PCI. The cumulative probability of brain metastasis without PCI was 36% at 12 months and 47% at 24 months; the probabilities were 6 and 10%, respectively with PCI. The 24-month probability of brain metastasis in patients with limited disease and no PCI was 45%; for those with extensive disease, it was 47%. No patient presented with extracranial central nervous system (ECNS) metastasis and no one without PCI developed it. Twelve patients who received PCI developed ECNS metastasis; the cumulative probabilities rose to 14% at 12 months and 22% at 24 months. The increased frequency of ECNS involvement has led to a phase I trial of PCI followed by six cycles of combination chemotherapy, without maintenance chemotherapy, followed by irradiation of the chest and spinal cord for patients with complete response.

Brain↗