Biomedical subjects

J D Cox

Publications and source records attributed to J D Cox.

243 records · Page 14Linked to original sources

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Standards for diagnosis and management of invasive breast carcinoma. American College of Radiology. American College of Surgeons. College of American Pathologists. Society of Surgical Oncology.

Because knowledge has advanced in several fields related to the treatment of early breast cancer, revising the landmark 1992 standards for breast-conservation treatment by these four organizations is appropriate. The current report reviews and summarizes the literature and describes the selection and evaluation of patients, the technical aspects of surgical treatment and irradiation, follow-up care, and areas for further research.

Antineoplastic Combined Chemotherapy Protocols↗

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Evidence in oncology. The Janeway lecture 2000.

PURPOSE: The purpose of this address is to evaluate the types of evidence that have fashioned clinical decision making in oncology over the past century and to determine the appropriate weighting of evidence at the start of a new century in the shaping of patient care, clinical research, and health policy. METHODS: Three separate analytic approaches were used: (1) a review of publications that altered medical practice, (2) a consideration of the misperception that little progress has been made by looking at the relationship between 5-year survival rates and national mortality rates, (3) an evaluation of the quality of data from clinical trials. RESULTS: Published reports suggest that res ipsa loquitur was the dominant mindset of researchers in the first half century and continuing into the second half century. However, recognition of the scarcity of dramatic improvements in outcome and the possibility of incremental improvements led to the mounting of prospective randomized comparative trials that could identify such incremental improvements. Findings from these trials have profoundly altered patient care in the past quarter century. Data suggest that there is a sequence of events-increased survival rates in patients at research institutions followed by significant increases in survival rates nationally-followed by a reduction in annual mortality rates that do reflect improvements in treatment. Phase III comparative clinical trials yield the highest quality data in oncology. Meta-analysis of such data may be useful, but the most compelling data that alter medical practice come either from comparative clinical trials showing such significant differences in results as to necessitate their early termination on ethical grounds or from replicated phase III trials. DISCUSSION: The nature of evidence influencing clinical practice and research has changed greatly in the past century. Although res ipsa loquitur still pervades the thinking of some oncologists, recognition of the incremental nature of progress is now the more dominant force in contemporary oncologic research. In addition, as molecular targets become the focus of therapeutic efforts, it will be especially important to proceed as quickly as possible to phase III comparative trials rather than to phase II studies.

Clinical Trials as Topic↗

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Methodology and research by the Radiation Therapy Oncology Group (RTOG).

The studies of the Radiation Therapy Oncology Group have contributed important evidence to improve the outcome of patients with cancer. The evidence has been compelling both to the scientific community and to practicing physicians a very large number of whom participated in the investigations. It is a tribute to the hard work of these many hundred volunteers that the studies mentioned above, and many other clinical investigations were completed, and patients throughout the world had improved outcomes.

Female↗

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Radiation Therapy Oncology Group (RTOG) trials for head and neck cancer.

Clinical investigations for cancer of the head and neck, primarily tumors of the upper respiratory and digestive tracts, have been one of the most important components of the Radiation Therapy Oncology Group (RTOG) since its inception 30 years ago. Emphasis from the very beginning to the present time has been on altered fractionation. Studies of hypoxic cell sensitizers were also explored for many years. More recently, combinations of radiation therapy with cytotoxic chemotherapeutic agents, either sequentially or concurrently, have been a major focus. Although the majority of the trials have been for unresectable tumors, surgical adjuvant radiation therapy alone or combined with chemotherapy has also been an important activity. Combined modality trials emphasizing organ conservation have been carried out within the last decade. The RTOG represents a national and international resource for studies of cancer of the head and neck. Its results influence the care of patients and the clinical research environment.

Dose Fractionation, Radiation↗

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Results of whole-brain irradiation for metastases from small cell carcinoma of the lung.

Prophylactic brain irradiation significantly reduces the proportion of patients with small cell carcinoma of the lung (SCCL) who develop brain metastases. Therapeutic brain irradiation could be used instead of prophylactic irradiation if it could be delivered promptly after diagnosis of intracranial spread and if it were highly effective. Forty of 188 patients with SCCL seen in the Medical College of Wisconsin Affiliated Hospitals had brain metastases either at initial diagnosis (23 patients) or after treatment (17 patients). Irradiation was administered to the whole brain at doses ranging from 3000 rads in 2 weeks to 4000 rads in 3 weeks. Neurologic function was the same for those patients with initial and delayed metastases and did not correlate with survival. Response to irradiation affected survival. After the diagnosis of brain metastases, survival was the same whether metastases were initially present or were delayed. Eighteen (45%) of the patients died from brain metastases and two (5%) are alive following disease recurrence in the brain. Increasing survival with SCCL due to effective chemotherapy is associated with an increasing failure rate in the brain which may eventually reach the 50% rate found at autopsy. Therapeutic brain irradiation is not sufficiently effective to preclude prophylactic irradiation.

Adult↗

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Risk of brain metastasis from small cell carcinoma of the lung related to length of survival and prophylactic irradiation.

The problem of brain metastasis from small cell carcinoma (SCC) of the lung has been appreciated for many years, but the magnitude of the problem has been underestimated. Recent studies have shown that the risk of brain metastasis increase as survival is prolonged. Although prophylactic cranial irradiation (PCI) has reduced the frequency of brain metastases, the effect on risk estimates of differences in the periods of observation was not evaluated. From 1974 through 1979, 131 patients with SCC of the lung who had no evidence of brain metastasis by radionuclide or computerized tomographic scan were treated in the Division of Therapeutic Radiology at the Medical College of Wisconsin Affiliated Hospitals. PCI was started in 1977; 57 patients received it and 74 did not. To correct for the differing periods of observation for the two groups, an actuarial calculation of the probability of brain metastasis was used. The calculated rate of clinical failure in the brain for patients who did not receive PCI was 28% at 12 months and 58% at 24 months. The calculated failure rate of the brain for patients who received PCI was 11% at 12 and 24 months. The difference in the probability of brain metastasis between the patients who did or did not receive PCI is highly significant (P less than 0.01). The true benefit of PCI becomes apparent only when the risk of intracranial metastasis is evaluated by methods that correct for incomplete followup. PCI eliminates the progressive increase in the risk of brain metastasis that accompanies increased survival and is important to maximize the probability for cure of patients with SCC.

Adult↗

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The role of radiation therapy for carcinoma of the lung.

A large proportion of patients with carcinoma of the lung may benefit from the use of radiation therapy. Operable patients have not been shown to benefit from preoperative irradiation, but postoperative irradiation has improved survival in those found to have involvement of hilar or mediastinal lymph nodes. Radiation therapy is the only potentially curative treatment for patients who are inoperable, but do not have distant metastasis. Control of the local tumor is very dependent upon dose-fractionation-time relationships. Patients who are relatively asymptomatic, i.e., they have a high performance status, are curable if treated promptly with radiation therapy. Small cell carcinoma requires both radiation therapy and chemotherapy. The optimal method of combining the two modalities is yet to be determined, but prophylactic cranial irradiation is necessary to control microscopic metastases that are not affected by systemic chemotherapy, and thoracic irradiation is necessary to give the highest probability of control of the primary tumor. Prophylactic cranial irradiation has also been shown to reduce the frequency of brain metastasis in patients with squamous carcinoma, large cell carcinoma, and adenocarcinoma; it may become more important in these cell types when more effective chemotherapy is developed.

Brain Neoplasms↗

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Causes of treatment failure and death in carcinoma of the lung.

Studies of patterns of failure and causes of death have been undertaken based upon the WHO histopathologic classification. In a randomized trial of thoracic irradiation +/- chemotherapy (hydroxyurea and CCNU), patterns of failure did not seem to differ by cell type; the largest group was "death without progression." A subsequent clinical trial of thoracic irradiation +/- cranial irradiation permitted a more detailed evaluation. Patients with squamous cell carcinoma had a higher rate of local failure than distant metastasis. Those with small cell carcinoma had a lower local failure rate and a high rate of distant spread. Patients with adenocarcinoma and large cell carcinoma had the lowest local failure rate, but had a high rate of distant metastasis. In 300 consecutive patients with autopsies, 75 percent with squamous carcinoma died of complications of the thoracic tumor and only one-quarter had extrathoracic dissemination; 30 percent with small cell carcinoma died of local tumor complications and 70 percent had carcinomatosis; 40 percent of patients with adenocarcinoma and large cell carcinoma died of intrathoracic complications, and 55 percent had distant metastases. Half the patients with small cell carcinoma, large cell carcinoma, and adenocarcinoma had brain metastases at autopsy. Future clinical trials should emphasize better control of the most common sites of failure.

Adenocarcinoma↗

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Irradiation for inoperable carcinoma of the lung and high performance status.

Disagreement continues about the role of immediate irradiation of asymptomatic patients with inoperable lung cancer. Information pertaining specifically to irradiation of asymptomatic patients is scarce. The Medical College of Wisconsin, Milwaukee, reported that survival two years after irradiation was affected by control of the intrathoracic tumor. Ninety-two patients from that study with high performance status (80 to 100 on the Karofsky scale) were evaluated for long-term survival. Of 54 patients (59%) whose tumors were controlled locally by irradiation, 22% survived five years. None of the 38 patients with uncontrolled thoracic disease lived beyond 27 months. Eight patients are alive and well 53 to 100 months after treatment. No specific late complications of irradiation have been seen. Patients having few symptoms with inoperable bronchial carcinoma can live many years if the tumor is controlled by irradiation.

Adult↗