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Biomedical subjects

F R Hendrickson

Publications and source records attributed to F R Hendrickson.

At least 55 records · Page 3Linked to original sources

Response of pancreatic cancer to local irradiation with high-energy neutrons.

Seventy-seven patients with locally advanced, nonresectable, biopsy-proven adenocarcinoma of the pancreas were treated by palliative bypass surgery followed by intensive neutron beam irradiation of the primary tumor site. Three dose levels, under 20, 21 to 23, and 24 to 25 Gy, were studied with the use of a treatment plan that included all known disease within a limited target volume, generally under 2 l. Symptomatic palliation was achieved in the majority of patients. The median survival time was 6 months. One patient remained alive and well without evidence of tumor 5 years after irradiation. Two were free of tumor at autopsy (one had died of intercurrent disease and one of radiation-related complications). A common cause of death was metastatic dissemination. Complication rates were dose-dependent; life-threatening complications did not exceed 12% with doses of less than 23 Gy. Autopsies from 19 patients were reviewed. In all, the pancreatic tumor site showed extensive reactive fibrosis. Local control was achieved in two patients, but most had both residual tumor in the pancreas and metastases. Six patients had centrolobular veno-occlusive liver disease. These patients had all received the higher (22-24 Gy) neutron doses. Six patients had hemorrhagic radiation gastroenteritis. Mild skin atrophy and bone marrow hypoplasia were seen in the irradiated volumes. The kidneys and spinal cord showed no radiation effects. The authors conclude that neutron irradiation can provide a good local response with marked regression and fibrosis of the tumor. This response, coupled with many deaths due to metastases, suggests that combined treatment with neutrons and chemotherapy would be worth exploring.

Adenocarcinoma↗

Radiation therapy treatment of larynx cancers.

Cancers in the mouth and throat area comprise only 5% of all cancers seen in the US. Because of their critical location and the various consequences of treatment, they produce a devastating impact on the quality of life. Of the many anatomic sites in the upper air and food passages, the oral cavity and larynx are involved with cancer in two thirds of the patients. In the oral cavity, less than 50% of the cancers are diagnosed when the disease is still localized, leading to a generally poor overall result. In the larynx, two thirds of the primaries arise in the glottis where hoarseness stimulates early diagnosis, leading to an excellent prognosis. Treatment strategies must be directed toward the observed patterns of failure. For mouth and throat cancers, even when modestly advanced, distant failure is observed in fewer than one third of the patients. Control of the disease in the primary site and regional node stations generally employs aggressive use of surgery, radiation therapy, or a combination of the two. More recently, the use of chemotherapy programs combined with either surgery or radiation therapy has been of benefit to patients with advanced lesions. The choice of a specific management program depends upon (1) the cancer control to be expected, (2) the effectiveness of a possible salvage treatment program, and (3) the quality of life experienced by the successfully treated patient. Radiation therapy is increasingly becoming the treatment of choice for early carcinomas of the larynx. Recently published results from four major institutions embracing over 4000 patients suggest radiation therapy cure rates for T1 lesions of 90% and T2 lesions of 70%, with the successful salvage by surgery of more than 50% of the radiation therapy failures, bringing the ultimate cure rate to over 95% for T1 lesions and over 85% for T2 lesions. The excellent results coupled with the good quality of life mandates this approach. Surgical alternatives are more frequently suggested for T3 lesions or for supraglottic lesions. Primary radiotherapy for T3 glottic lesions currently cures more than 50% of such patients with surgical salvage, bringing the total cure rate to 75%. Also two thirds of the cured patients retain their functioning larynx, increasing consideration must be given to primary radiation therapy and surgical salvage for these more advanced glottic lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Combined Modality Therapy↗

Clinical evaluation of neutron beam therapy. Current results and prospects, 1983.

Some 9000 patients throughout the world have been treated by some form of neutron beam therapy. These include patients with advanced nonresectable tumors in many different sites treated with a variety of neutron beam generators varying widely in beam energy. Protocols were largely nonrandomized and included both mixed beam studies (neutrons + photons) and neutrons alone in varying doses. In spite of wide variation in equipment, treatment technique, and philosophy, some consistent trends have been identified: (1) in general, the neutron results have been at least as good as those of the photon controls measured in terms of local control, although the incidence of significant side effects have been higher; (2) in none of the randomized studies conducted so far, largely comprising epidermoid carcinomas of the head and neck, has a clear survival advantage for neutrons over photon controls been demonstrated at a statistically significant level; (3) results with mixed beam studies have been uniformly equivocal, with marginally significant differences in favor of the experimental groups compared with the photon controls; (4) adenocarcinomas of the gastrointestinal tract (GI) tract, including tumors of the salivary gland, pancreas, stomach, and bowel, appear to be responsive to high linear energy transfer (LET) radiation; (5) nonepidermoid, radioresistant tumors (sarcoma of bone and soft tissue and melanoma) yield a consistantly high local control rate, with neutron irradiation strikingly superior to those reported with photon therapy; and (6) in the central nervous system, both normal tissues and tumors appear to be exceptionally sensitive to neutron irradiation, therapeutic ratios are small, and the prospect of cure remains remote. It is concluded that neutrons are efficacious for certain specific tumor types, but that essentially new study designs, based on nonrandomized matched case comparisons, will be required to prove the merit of the new modality.

Adenocarcinoma↗

Carcinoma of the nasopharynx: survival and patterns of recurrence.

We have analyzed survival, disease-free (NED) survival, and patterns of recurrence for 76 patients with carcinoma of the nasopharynx treated from June 1964 through July 1979. Patients with Stages I through IV, who were treated for cure, comprise the study group. Megavoltage teletherapy treatment was delivered to the primary bilateral neck and supraclavicular areas. Dose to the nasopharynx ranged from less than 55 Gy to 70 Gy with several patients receiving higher doses. The observed 5 year NED survival rates were: Stage I, 75%; Stage II, 20%; Stage III, 42%; and Stage IV, 31%. During a 5-year minimum follow-up for all patients, 46 or 60.5% failed. Ninety-five percent of these failures occurred within 3 years; only two patients relapsed after more than 5 years.

Adolescent↗

Fast neutron radiotherapy for locally advanced prostate cancer: results of an RTOG randomized study.

Between June 1977 and April 1983, the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized study investigating fast neutron radiation therapy in the treatment of patients with locally advanced (Stage C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation therapy or fast neutron irradiation used in a mixed-beam treatment schedule (neutron/photon). A total of 91 analyzable patients were entered in the study; 78 of them were treated without major protocol deviations. The two treatment groups were balanced in regard to all major prognostic variables. Actuarial curves for "overall" survival, "determinantal" survival and local/regional control are presented both for the entire group of 91 patients and the 78 patients treated within protocol guidelines. The overall local/regional tumor recurrence rate is 7% for the mixed-beam treated group of patients and is 22% for the photon (X ray) treated group of patients. The difference is statistically significant at the p = 0.05 level. For the entire group of 91 evaluable patients, the 5-year "overall" survival rate is 62% for the mixed-beam-treated group and 35% for the photon-treated group. This difference is also statistically significant (p less than 0.05). However, this statistical significance is lost when the smaller number of patients treated strictly within protocol guidelines is considered. The significance is regained (p less than 0.02) when one looks at "determinantal" survival, which uses active cancer at time of death as the failure endpoint. This study demonstrates that a regional treatment modality, in this case mixed-beam irradiation, can influence both local/regional tumor control and survival in patients with locally-advanced adenocarcinoma of the prostate gland.

Adenocarcinoma↗

Fast neutrons and misonidazole for malignant astrocytomas.

Twenty-five patients with biopsy proven malignant supratentorial astrocytomas were entered into a Phase I/II study of misonidazole combined with neutron radiation at Fermilab Neutron Therapy Facility (NTF) between August 1979 and April 1981. The main objectives were to determine tissue tolerance in terms of acute and late effects, and to estimate tumor clearance and survival rates. The total dose was 18.0 Gy given in weekly fractions of 3.0 Gy over 39 days. Four hours before each irradiation, 2.5 gm/m2 misonidazole was administered orally. Patients' ages ranged from 28-69 years. Karnofsky status for most patients was 80 or 90; the lowest grade was 60. The majority of patients had glioblastoma multiforms. Most were already on steroids prior to initiation of therapy. The median survival for the whole group was 12.0 months; 25% were alive at 18 months with some neurological compromise. The median survival remained unchanged for subgroups of patients with ages between 40-60 years and with Karnofsky performance status above 80. Among the 19 patients with glioblastoma multiforme, the median survival was 10 months. Acute toxicity was within tolerable limits. Details of toxicity and tissue analysis from post mortems and second craniotomy samples are presented.

Adult↗

Tolerance of the human spinal cord to high energy p(66)Be(49) neutrons.

The risk of post irradiation myelopathy was evaluated in 76 patients followed for 1-5 years after neutron irradiation of the cervical and thoracic regions. No overt myelopathy was observed. Forty-six patients received doses (central cord dose) in excess of 10 Gy, 9 received doses in excess of 12 Gy, and 5 received doses between 13 and 17 Gy, all without any evidence of spinal cord injury. On careful questioning, a subjective transient neuropathy (a tingling sensation in one extremity) was reported by 6 patients, but this was apparently unrelated to dose. A review of available literature revealed a total of 14 patients with myelopathy, 13 of whom received doses in excess of 13 Gy delivered with relatively low energy neutrons generated by the deuteron + beryllium reaction. It is concluded from these studies that the tolerance limit for the human spinal cord irradiated with high energy [p(66)Be(49)] neutrons is close to 15 Gy, above which the risk of cord injury becomes significant. Central cord doses of 13 Gy or less appear to be well tolerated with little, if any, risk of myelopathy. These conclusions are valid for a treatment time of 4 weeks or more with two or more fractions per week (9 or more fractions). The RBE for the human spinal cord irradiated under the above conditions compared with conventionally fractionated photon therapy does not exceed 4.0.

Adult↗

Absence of major depressive disorder in female cancer patients.

This investigation evaluated the prevalence of depression in female patients who had cancer in any of five predesignated sites. Five hundred five women aged 17 to 80 (190 with breast cancer, 143 with gynecologic malignancies, 111 with melanoma, 37 with bowel cancer, and 24 with lymphoma) were randomly screened. Assessment included the Hamilton rating scale for depression, the Zung self-rating depression scale, the Karnofsky performance scale, and a 10-cm visual pain analogue line. The results revealed a mean Hamilton of 10.2 (range, 0 to 41; SD, 7.5), a mean Zung score of 35.3 (range, 11 to 68; SD, 9.6), a Karnofsky median score of 80, and a median pain score of 0. Scores on the Zung scale were highly correlated with those of the Hamilton scale (r = .75). Based on cutoff scores accepted as indicating depression (Hamilton greater than or equal to 20 and Zung greater than or equal to 50), patients were depressed. The depressed subgroup was in significantly more pain, experienced greater physical disability, and was more likely to have had prior episodes of depression as compared to the non-depressed women. The two best predictors of current depression were performance status (Karnofsky) and history of depression. No relationship was found between depression and other demographic variables or disease parameters (diagnosis, time since diagnosis, stage or phase of illness, and current treatment). Our findings indicate that the prevalence of major depression in cancer patients is lower than many previous studies have indicated and falls within the range seen in the general population.

Adolescent↗

Review of clinical results of fast neutron therapy in the USA.

Fast neutron radiotherapy in the United States is entering a new era in which dedicated hospital-based generators with isocentric beam capability are replacing treatment facilities based on fixed beams extracted from physics accelerators. All available clinical data, however, come from the older facilities. The majority of randomized trials conducted in the U.S. have used neutrons in a mixed schedule with photons, in which the aim was to deliver two-fifths of the total dose with neutrons; the neutron dose per fraction was set as the estimated equivalent of 2 Gy photons in terms of late normal tissue injury. Overall treatment time was held constant compared with the control photon therapy regimens (usually six to eight weeks). Random studies of this type showed no evidence of a therapeutic gain in the treatment of advanced primary carcinomas of the head and neck, lung, uterine cervix, or pancreas. A statistically significant benefit in favor of the mixed schedule is presently apparent for local control and survival in patients with advanced prostate cancer, and for clearance of neck nodes in patients with advanced squamous carcinoma of the head and neck. Based on encouraging results in a pilot study of mixed scheduled irradiation preoperatively for bladder cancer, a random study was begun in 1981, but too few cases have been accrued for analysis. Other randomized trials comparing protracted neutron only regimens with photon therapy have been conducted. These were negative for lung and pancreatic cancer, but a suggestion of a therapeutic gain (with small patient numbers) has been observed for treatment of inoperable salivary gland tumors and advanced squamous carcinomas of the head and neck. Two large randomized studies of various neutron doses delivered as a boost to high grade astrocytomas after or concurrently with photon irradiation have failed to define any therapeutic window between tumor destruction and brain necrosis. Based on a reassessment of all the available clinical and radiobiological data, and taking advantage of the greater technical flexibility offered by hospital-based facilities, the strategy of fast neutron therapy for future trials has been changed. In these trials neutrons are being used in a twelve fraction, four week regimen to treat gross disease, with elective therapy being given wherever possible using low LET irradiation. Concomitantly, research is proceeding to define predictors of tumor response to high LET radiations in order to better select patients for fast neutron radiotherapy.

Fast Neutrons↗

Radiation Therapy Oncology Group Phase I-II study on fast neutron teletherapy for carcinoma of the bladder.

From June 1977 through March 1981, the Radiation Therapy Oncology Group sponsored a Phase I-II study (RTOG 77-05) on the use of fast neutrons for treating carcinomas of the urinary bladder. Patients entered on the study had Stage B1 (grade III or IV histology) or Stage B2, C, or D1 (any grade histology) disease. Thirteen patients received preoperative mixed-beam (neutron/photon) irradiation to 50 photon Gy-equivalent, and in 12 of these a cystectomy was performed in 4 to 6 weeks. The incidence of pathologic downstaging to Po was 58% in the cystectomy specimens. The projected survival at 30 months is 32%. Twenty-six patients were treated definitively with mixed-beam irradiation consisting of 50 photon Gy-equivalent to the pelvis followed by a 20 photon Gy-equivalent boost to the bladder itself. Eighteen of 26 patients (69%) achieved tumor clearance at some time during their follow-up but 8/18 (44%) of these ultimately exhibited some component of local failure. The projected survival at 30 months for this group of patients is 34%. However, the subset of patients with Stage B or C disease had a projected survival at 30 months of 60%. Four patients received definitive neutron irradiation alone and 3/4 achieved tumor clearance at some time during their follow-up. Actuarial curves are presented for patient survival and duration of local control, and results are compared with comparably staged patients treated with megavoltage photon irradiation. Treatment-related morbidity is also discussed.

Aged↗

Response of epidermoid and non-epidermoid cancers of the head and neck to fast neutron irradiation: the Fermilab experience.

One hundred and six patients with locally advanced cancers of the head and neck were treated with neutrons at the Fermilab Neutron Therapy Facility. Of these, 44 patients were previously untreated, 33 were recurrent following attempted surgery and 29 patients had previously received a full course of radiation therapy with conventional radiation. Results were analyzed to study the influence of stage, previous management, site of origin and tumor histology on local control of the disease. The most significant factor determining the outcome in this series of patients is the histological type. For epidermoid carcinoma, long term local control was achieved in 17/35 patients (49%) in the previously unirradiated group. With non-epidermoid tumors (adenocarcinoma, cylindroma, muco-epidermoid carcinoma), the local control rate was 28/39 (72%). Disease-free survival analysis also shows a survival advantage in non-epidermoid lesions treated with neutrons. It is concluded that neutron beam therapy may probably be the treatment of choice for non-resectable or recurrent non-epidermoid cancers of the head and neck and requires a clinical trial to establish this observation.

Adenocarcinoma↗

Mixed beam radiation therapy for unresectable squamous cell carcinomas of the head and neck: the results of a randomized RTOG study.

Three hundred and twenty-two patients with inoperable squamous cell carcinomas of the head and neck were entered on a randomized study comparing "mixed beam" radiation therapy with photon radiation therapy. Patients with histologically proven tumors of T-stage T2, T3, or T4 and any N-stage originating in the oral cavity, oropharynx, supraglottic larynx, or hypopharynx were eligible. One hundred forty-five patients were randomized to photon treatment and 177 were randomized to mixed beam treatment. No significant differences could be demonstrated between the experimental and control groups for primary tumor control or overall survival, although there was an advantage for mixed beam treatment over photon treatment for patients with metastatic cervical adenopathy (69 vs. 55% complete response rate in the nodes, p = .024). It is concluded that mixed beam radiation therapy does not offer a significant advantage over photon radiation therapy for patients with advanced squamous cell carcinomas of the head and neck.

Aged↗

Fast neutron radiation therapy for unresectable squamous cell carcinomas of the head and neck: the results of a randomized RTOG study.

Forty patients with advanced, unresectable squamous cell carcinomas of the head and neck were entered on a prospective, randomized study comparing fast neutron radiation therapy with conventional photon radiation therapy. Twenty-six patients were randomized to neutrons, and 14 patients were randomized to photons. The randomization was purposefully unbalanced in favor of the experimental treatment. The complete response rate for the neutron-treated group of patients was 52%. The complete response rate for the photon-treated group of patients was 17%. The difference is statistically significant at the p = .04 level. The two-year survival rates for the neutron-treated group and the photon-treated group were 25 and 0%, respectively. The major complication rates were not statistically significantly different for the two groups (18% for neutrons, and 33% for photons).

Aged↗

The role of radiation therapy in the palliation of metastatic genitourinary tract carcinomas. A study of the Radiation Therapy Oncology Group.

The Radiation Therapy Oncology Group has conducted several randomized clinical trials to evaluate the efficacy of various radiation therapy schedules in palliating symptomatic brain and bone metastases. Among the patients entered in these studies, there were 225 patients with primary tumors of the genitourinary tract. Of these, 68 patients had cerebral metastases and 157 patients had osseous metastases. These patients were analyzed further as to the effectiveness of radiotherapy in palliation of their symptoms, and the results were compared to those for comparable metastases in patients with other primary sites. Relief of symptoms occurred in 54% of neurologic function (NF) Class III and 28% of NF Class II patients with cerebral metastases. This result compared favorably with those for the total group of patients consisting of patients with brain and bone metastases from various primary sites. Improvement was seen in 80% of patients with headaches and 88% of patients with convulsions. Motor loss improved in 62% of the patients. Of the patients with bone metastases, 81% with prostatic carcinoma and 59% with renal primaries had lessening of pain. Complete relief of pain at eight weeks occurred in 36% of the patients, compared to 24% in the total group. The median survival for patients with solitary bone metastases from a prostatic primary was 39 weeks, compared to 30 weeks for those with multiple metastatic sites.

Bone Neoplasms↗

Definitive irradiation of T1-T4N0 larynx cancer.

The use of definitive irradiation in T1-T4N0 larynx cancer was reviewed in 236 patients at Rush-Presbyterian-St. Luke's Medical Center in Chicago. Recurrence-free survival for all stages was 86% at five years. Ultimate recurrence-free survival, including successful surgical salvage, was 91% at five years. The data described herein and the literature reviewed support the recommendation for definitive radiation therapy for T1 and T2N0 larynx cancer of any site. T3 lesions may also be reasonably treated with radiation therapy initially, reserving surgery for salvage. However, more data are needed to accurately identify the T3 larynx cancer patients most suited for radiation therapy.

Adult↗

The influence of surgery and radiation therapy on patients with brain metastases.

The place for operation and for radiation therapy in the management of brain metastases is reviewed from the experience of 1895 patients treated in two studies of the Radiation Therapy Oncology Group. Operative removal may be of benefit to patients with solitary peripheral lesions in non-critical brain locations. Operation is also appropriate when the diagnosis is in doubt. Radiation therapy with appropriate steroid management is of benefit to patients with multiple metastases or where operative intervention is not reasonable. Short course low-dose treatment has been as beneficial as more aggressive prolonged radiation therapy.

Brain Neoplasms↗

Fast neutron irradiation of metastatic cervical adenopathy: the results of a randomized RTOG study.

Between 1977 and 1982, 199 evaluable patients with measurable cervical adenopathy were entered on a prospective, randomized RTOG study evaluating the use of fast neutrons in treatment of advanced, inoperable squamous cell carcinomas of the head and neck region. One hundred-eleven patients were randomized to receive mixed beam radiation therapy, and 88 were randomized to the photon control treatment. The complete response rates were 86% for mixed beam vs 75% for photons for Stage N1 nodes, 62% for mixed beam vs 48% for photons for Stage N2 nodes, and 63% for mixed beam vs 53% for photons for N3 nodes. The percents of patients remaining free of their adenopathy for two years were 78% for mixed beam vs 55% for photons for Stage N1 nodes, 39% for both mixed beam and photons for N2 nodes and 24% for mixed beam vs 13% for photons for N3 nodes. The median disease-free status was 20.3 months for mixed beam treated patients and 6.4 months for photon-treated patients. Patients who had clearance of cervical adenopathy survived significantly longer than those who did not.

Carcinoma, Squamous Cell↗