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Biomedical subjects

G H Fletcher

Publications and source records attributed to G H Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed1984

Lucy Wortham James Lecture. Subclinical disease.

A number of patients with cancer later develop metastases in the draining lymphatics, which initially were clinically negative. These occult deposits represent subclinical disease in lymphatic areas accessible to palpation, like the neck, axillae, and groin. The concept applies also to the microscopic disease left in an area after a surgical procedure is known to have removed all gross cancer, yet some patients later develop a recurrence. The term "subclinical disease" refers only to disease in a specific anatomic area, based on clinical facts. Radiobiological parameters account for the fact that subclinical disease requires less irradiation to be eradicated than gross cancer. The concept has two main applications, elective irradiation of clinically negative peripheral lymphatics and locoregional irradiation combined with surgery, which are determined by site and disease. The concept of subclinical disease also has implications for chemotherapy, which bear a direct relationship between chemotherapy both with radiation therapy and surgery.

Axilla↗
PubMed1984

Malignant mixed Müllerian tumors of the uterus.

One hundred and eight patients with a diagnosis of malignant mixed müllerian tumors of the uterus treated at the M.D. Anderson Hospital from 1948 through 1977 were analyzed. Pathology was reviewed and subdivided according to the sarcomatous element. No difference in pattern of recurrence or survival could be demonstrated between homologous, heterologous, or undifferentiated sarcomatous elements. Nine patients were treated with only palliative intent due to advanced local disease combined with poor medical condition. Of the remaining 99 patients, 87% had minimum surgical procedures of total abdominal hysterectomy. All but two of these patients had adjunctive radiation either preoperatively or postoperatively. The 5-year survival rate was 38%. There was frequent upstaging at surgery in all stages except IA. Patients with tumor confined to the uterus at the time of surgery had a 5-year disease-free survival of 52%. When there was extension outside of the uterus, the 5-year disease-free survival dropped to 28%. The locoregional recurrence rate was 17%.

Combined Modality Therapy↗
PubMed1984

Twice-daily fractionation schemes for advanced head and neck cancer.

Eighty-five patients with advanced squamous cell carcinoma of the head and neck were treated with twice-a-day fractionation schedules between April 1972 and December 1980. Two types of treatment were distinguished: hyperfractionation, by which 65 patients (Group I) were treated at a weekly dose rate of 1100 to 1200 rad (10 fractions of 110 to 120 rad) in 5 to 6 1/2 weeks for either advanced primary disease (Group 1A) and/or advanced neck metastases (Group IB); and accelerated treatment, used to treat 20 patients (Group 2) who had fast-growing and usually massive neck nodes, at a weekly dose rate of 1300 to 1500 rad in 7 to 10 fractions, to a total dose of 6100 to 8000 rad in 4 to 6 weeks. The radiation portals for patients in Group 2 excluded the mucosa of mouth and throat for part of the treatment. The local control rate at 1 year in Groups 1A and 1B was 41 and 54%, respectively; the incidence of complications was 17%, 5% of them fatal. The local control rate in Group 2 was 80%. Seven patients in this group underwent a neck dissection 6 to 8 weeks following irradiation. Four specimens were negative for tumor. In two, only necrotic tumor cells were identified, and in one specimen morphologically intact tumor cells were seen. There were no fatal complications.

Carcinoma, Squamous Cell↗
PubMed1984

Radiation and drug resistance of breast cancer.

There are clinical data correlating the control rates of adenocarcinoma of the breast with doses of irradiation and the volume of cancer. As the volume of cancer increases, doses have to be increased to obtain significant control rates. Of particular interest is subclinical disease, i.e., occult aggregates of cancer cells that cannot be palpated in areas accessible to palpation. Almost 100% of subclinical disease can be controlled with 4,500-5,000 rad in elective irradiation of clinically uninvolved lymphatics, whereas gross masses in excess of 5 cm in diameter require doses of 8,000-10,000 rad. The radiobiological explanations for these differences are 1) the randomness of cell killing, 2) hypoxia, and 3) repopulation. Using the same methodology of survival fractions there are now experimental data showing that resistance to drugs is a function of the number of clonogens and that hypoxic cells are also more resistant to drugs. Using the spheroid technique, it has been shown that cells centrally located in a spheroid are not affected by the drugs. Therefore, there is also a mechanical reason for drug resistance. In the last few years it has been postulated that mutations in the tumor cell population render some cells resistant to certain drugs. The often made statement that the development of permanent resistance more precisely accounts for the greater effectiveness of combination chemotherapy over single agents is discussed in the light of data from clinical trials.

Adenocarcinoma↗
PubMed1983

Accelerated fractionation vs hyperfractionation: rationales for several treatments per day.

Treatment with several doses per day offers the prospect of a significant therapeutic gain using readily available low LET beams. These regimens can be classified as either accelerated fractionation or hyperfractionation according to their rationales. With accelerated fractionation a conventional number of dose fractions is delivered in a significantly shortened overall treatment time in order to reduce the opportunity for tumor cell regeneration during treatment. With hyperfractionation, on the other hand, a large number of significantly reduced dose fractions is used to give a greater total dose in a conventional overall treatment time. The rationale for this strategy is threefold: 1) increased opportunity for tumor cell redistribution and reoxygenation between dose fractions: 2) a possibly lower oxygen enhancement ratio with small incremental doses; and 3) different sparing of late reacting normal tissues with small dose fractions. A review of the published clinical experience with multiple fractions per day treatment reveals few studies of either pure accelerated fractionation or hyperfractionation since both are limited by acute normal tissue reactions. This has led to a variety of hybrid regimens, some of which have no clear rationale. The choice between accelerated fractionation and hyperfractionation is determined by the regenerative capability of tumor clonogens during treatment. A method of selection based on potential doubling times is presented.

Clone Cells↗
PubMed1983

Postoperative irradiation in malignant epithelial tumors of the parotid.

From 1954 through 1979, 77 patients with malignant tumors of the parotid gland were referred from the Department of Head and Neck Surgery for postoperative irradiation. The analysis has been made by grouping the patients according to the estimated amount of disease left after the surgical procedure and by the histological types. There were no local failures in the low-grade tumors, and there were 6 in the 63 patients with high-grade tumors. With gross residual disease or potential residual disease the patients received slightly higher doses than those without. Although there were only 6 failures in the various histological types, there was perhaps a trend to more failures in the adenocarcinomas. There was no difference in the failure rates in patients having had a total resection of the facial nerve or partial resection or no resection. The preferred treatment has been a combination of 20 MeV photons and 18 MeV electrons. Five neck failures were essentially a result of lack of elective irradiation of the neck. Severe complications appeared only in the patients irradiated either for gross residual disease or excision of a recurrence with a high risk of widespread microscopic residual disease.

Adolescent↗
PubMed1983

Analysis of the severe complications of irradiation of carcinoma of the cervix: whole pelvis irradiation and intracavitary radium.

From January, 1967 to December, 1974, 325 patients with carcinoma of the uterine cervix were treated with a minimum of 4,000 rad whole pelvis irradiation plus intracavitary radium. These patients had large, sometimes massive, tumors. Generally, the larger the primary tumor the greater the amount of external irradiation delivered, with an appropriate reduction in the amount of intracavitary radium. Patients who had a positive lymphangiogram or a pre- or postirradiation hysterectomy or lymphadenectomy are not included in this analysis. All patients were followed for a minimum of 5 years. Local and regional failure rate in 193 patients receiving 4,000 rad whole pelvis irradiation plus radium was 1% and 4%, respectively, with a 3.1% incidence of severe complications. In 111 patients who received 5,000 rad whole pelvis irradiation plus radium, the local and regional failure rate was 3.5% and 4.5%, respectively, with a 10% incidence of severe complications. In patients who received 5,000 rad whole pelvis irradiation, complications were associated with unilateral parametrial boosts and with protruding vaginal sources. Of 21 patients who received 6,000 rad whole pelvis irradiation, three patients developed fistulae associated with high doses to the vagina delivered with protruding vaginal sources.

Brachytherapy↗
PubMed1983

Keynote address: the scientific basis of the present and future practice of clinical radiotherapy.

At mid-century radiotherapy was more an art than a science, but is presently based on radiobiological parameters and cell kinetics. This close interaction between basic scientific principles and clinical practice has been made possible because one can correlate quantitatively doses of irradiation with observed responses. First, a short historical review will be made because it gives a perspective for the understanding both of progress made and prevailing misconceptions. The important radiobiological parameters and cell kinetics will then be discussed in some detail to demonstrate that they should be thoroughly understood in their relationship to radiotherapy. The overall treatment planning must be based on the clinical applications of the main radiobiological parameters. The combined treatment with surgery, either pre- or postoperatively, and multiple daily fractionations will be used as examples. The teaching of radiobiology should be considerably expanded, not only for its own scientific merit but also to show how it applies to clinical situations. This should be reflected in the expansion of the board examination.

Cell Survival↗
PubMed1983

Current concepts in radiotherapy and their impact on oncology.

The constant emphasis on the need for breakthroughs and new modalities of treatments seems to imply that nothing has been achieved, and unless new beams or radiation sensitizers or whatever are discovered, radiation therapy is ineffective. A great amount of information has been acquired in the past 20 years, and innumerable treatment schemes are being used with doubtful outcomes. The fact that patients are at high risk for development of distant metastases is irrelevant if one does not have a treatment that is effective. Multimodality treatments are very popular, but multimodality per se does not make a treatment effective. Medical research is anxious for early and repeated milestones. Cancer is a disease that requires follow-up and, in some areas, like breast cancer, a long follow-up. Baclesse, the great radiotherapist from the Curie Foundation, used to say in his teaching clinics that he was working for the next generation. Radiotherapy exists within the framework of medical practice. To emphasize systemic treatments because of the possibility of distant metastases and, by so doing, to deemphasize freedom of disease in the local area leads to abandoning methods of treatment that have proved effective for control of local-regional disease. An example is the abandonment of postoperative irradiation following mastectomy. It is not disputed that it achieves a very high degree of local and regional control, but it is disputed that it increases survival. Survival benefits with elective chemotherapy are marginally proved in small subsets of patients but do not demonstrably affect the survival rates of the overall population, and there is very little information concerning the local-regional control with elective chemotherapy. Survival benefits are not the only criteria of usefulness of a treatment. Gross recurrence is more difficult to eradicate than subclinical disease by elective irradiation, and there are a number of publications on the poor control of local-regional recurrences in breast cancer. Furthermore, some recurrences, such as invasion of the brachial plexus, are intractable to treatment; recurrences on the chest wall present a terrible problem of management as well as make the patient absolutely miserable prior to death. The present knowledge, primarily of the combination of radiation and surgery in certain diseases, is not applied except to a very small segment of the cancer patient population. The spread of information and the increased use of effective methods should be encouraged.

Breast Neoplasms↗
PubMed1983

Causes of failure of radiotherapy in head and neck cancer.

Causes of failure of radiation therapy are reviewed and illustrated with clinical examples from cancers of the head and neck region. Radiobiological factors relating to volume of cancer, hypoxia, tumor cell kinetics, intrinsic cellular radiosensitivity and repair capability are considered, along with physical factors relating to fraction size and inadvertent underdosage. In addition, reference is made to failures attributable to a sigmoid dose response curve for tumor control and to the development of second primary cancers. The distinction is made between those causes of failure that can be minimized by optimal application of concepts and techniques readily available to all radiotherapists, those that are not amenable to any modification of radiotherapeutic technique, and those that are potentially remediable by new treatment strategies based on the radiobiological attributes of individual tumors.

Dose-Response Relationship, Radiation↗
PubMed1983

A detailed analysis of the MDAH-TAMVEC neutron therapy trials for head and neck cancer.

The local control and survival rates with neutrons-only, mixed-beam, and conventional treatment were similar in the pilot studies, although the complication rate with mixed-beam irradiation was significantly less than that seen with the other treatment modalities. In the randomized trial, the local control and survival rates were better with mixed beam irradiation than with photons although the difference is not statistically significant. In this analysis, there were no tumor sites where any one treatment modality showed a marked superiority over another although neutron and mixed-beam therapy seemed to be most promising for faucial arch, base of tongue, pharyngeal wall, and salivary gland tumors. Analysis of the sites of failure indicated that neutron or mixed-beam therapy may be more effective than conventional radiotherapy in the management of regional lymph-node metastasis. In this study, dose-response relationships for local control and complications were demonstrated for the group treated with 50 MeVd leads to Be neutrons alone. The optimum dose was approximately 2100 radn gamma in 6 1/2 weeks, however, the range of acceptable neutron doses was narrow.

Clinical Trials as Topic↗
PubMed1982

Bilateral breast cancer in patients with initial stage I and II disease.

Between January 1947 and the end of 1975, of 2076 patients with Stages I and II breast cancer treated at M. D. Anderson Hospital, 126 received treatment for cancer in both breasts. Records of 94 patients who had only one cancer treated at U. T. M. D. Anderson Hospital and in whom staging and treatment details were not available and records of the patients who developed local, regional, or systemic failure prior to diagnosis of the second breast were excluded. Of 126 patients with bilateral breast cancer, 39 had simultaneous tumor (both cancers diagnosed within six months) and 87 had consecutive tumors. The disease-free 20-year survival rate shows no significant difference between patients with unilateral tumors and those with bilateral simultaneous or consecutive tumors. Analysis by radiotherapy modality or surgery alone shows, if anything, a lower incidence of cancer in the second breast in the irradiated patients, indicating that in patients with Stage I or Stage II lesions, the doses of radiation given in the management of the first breast cancer were not conducive to the development of a cancer in the remaining breast.

Breast Neoplasms↗
PubMed1982

Results in patients with breast cancer treated by radical mastectomy and postoperative irradiation with no adjuvant chemotherapy.

In 1963 an electron beam became available, making irradiation of the chest wall technically easy. In addition to peripheral lymphatic irradiation in patients with positive axillary nodes and/or the tumor in the inner quadrants or centrally located, patients with tumor larger than 5 cm or with grave signs and/or a significant incidence of positive axillary nodes received chest wall irradiation. None of the patients has received elective chemotherapy. Disease-free survival rates at ten years are 54% for the overall group, 79% for the patients with negative nodes, 44% for patients with positive nodes, 61% for patients with 1-3 positive nodes, and 33% for patients with four or more positive nodes. The incidence of peripheral lymphatic failures is low as well as the incidence of failures on the chest wall in the patients having had chest wall irradiation. With the availability of electron beam and adjustments in doses, complications are nonexistent. The incidence of treatment failures, local-regional, or distant, that have appeared by ten years are compared with the incidence of failures that were experienced by the placebo patients in the clinical trial of the NSABP of thio-TEPA versus placebo. The clearly lesser incidence of treatment failures in the U.T.M.D. Anderson Hospital patients either suggests that postoperative irradiation may have survival benefits or that the data of the NSABP series are not representative of all series.

Breast Neoplasms↗
PubMed1982

Analysis of the parameters relating to failures above the clavicles in patients treated by postoperative irradiation for squamous cell carcinomas of the oral cavity or oropharynx.

One hundred and two patients with squamous cell carcinoma of the oral cavity or oropharynx were treated from January 1955 through August 1976 with surgical excision followed by irradiation. Twelve patients had T2 lesions and 90 had T3 or T4 lesions. Failures above the clavicles were associated with disease present at the margins of resection, location of the recurrence close to the periphery, or outside of the irradiated portals. Failure in the neck essentially were a result of no elective irradiation. In patients with disease present at the margins of resection, there is a risk both of gross residual disease and hypoxic microscopic disease left behind; 4500 to 5000 rad is not adequate for a significant control rate. In situation where there is definite disease at the margin of resection, 6500 rad, or in specific situations, 7000 rad, should be given through reduced fields.

Carcinoma, Squamous Cell↗